April 2016 BUMC Proceedings - Blue Zones - Pag 220

Volume 29
Number 2
April 2016
The peer-reviewed journal of Baylor Scott & White Health
Scott & White Medical Center Temple
Baylor Scott & White Medical Center - Marble Falls
Baylor All Saints Medical Center at Fort Worth
Baylor Medical Center at McKinney
Baylor Scott & White Hospital - Hillcrest
Baylor Scott & White Medical Center - Round Rock
Baylor University Medical Center Proceedings
Baylor University Medical Center at Dallas
Volume 29, Number 2 April 2016

Pages 117260
www.BaylorScottandWhite.com
Review Article
131 Review of behavioral health integration in primary care at Baylor
Scott and White Healthcare, Central Region by J. B. Jolly et al
137 Invited commentary by C. Couch
Historical Article
138 Medical and surgical care during the American Civil War,
18611865 by R. F. Reilly
Baylor Regional Medical Center at Grapevine
The largest not-for-prot health care system in Texas,

and one of the largest in the United States, Baylor Scott
& White Health was born from the 2013 combination of
Baylor Health Care System and Scott & White Healthcare.
For more information on our 43 hospitals and more than
500 patient care sites, please visit www.BaylorHealth.com
and www.sw.org.
Original Research
119 The characteristics of Mohs surgery performed by
dermatologists who learned the procedure during residency
training or through postgraduate courses and observational
preceptorships by H. K. Steinman et al
124 Virtual reality and brain computer interface in
neurorehabilitation by D. B. Salisbury et al
128 Safety and efcacy of packed red blood cell transfusions at
different doses in very low birth weight infants by L. H. Mallett et al
Case Studies
143 Exercise-induced acute compartment syndrome in a young man,
occurring after a short race by B. Basnet et al
145 Table tipping and a near-miss fall after unlocking a surgical
table holding a morbidly obese patient by R. T. Booth et al
147 Use of ultrasound guidance to remove entrapped stimulating
popliteal catheters by R. K. McAllister et al
150 Baclofen-responsive hiccups after esophageal stenting for
malignancy-related dysphagia by V. Sharma et al
151 Specicity of testing in a cardiac rehabilitation setting resulting
in a patients return to high-intensity outdoor activity following
aortic dissection repair by S. Bartee et al
154 Invited commentary: Simulated performance testing to
determine the aortic dissection patients potential for vigorous
physical activity by B. A. Franklin
157 Cardiovascular autonomic neuropathy by N. McCarty and B. Silverman
160 Cardiac arrest refractory to standard intervention in atypical
Timothy syndrome (LQT8 type 2) by L. R. Phillipp and F. H.
Rodriguez III
163 Holter monitor recordings in a man who snores by D. L. Glancy
and P. Vijitbenjaronk
165 An interesting electrocardiogram by H. H. McClure Jr.
166 Takotsubo cardiomyopathy after administration of
norepinephrine by K. Sherif et al
168 Acute myocardial infarction with isolated congenitally corrected
transposition of the great arteries by J. Zimmerman et al
171 Isolated congenitally corrected transposition of the great arteries
with dextroversion discovered incidentally in a patient with
cocaine-induced acute myocardial infarction by A. Tandon et al
174 Invited commentary: The specialty of adult congenital heart
disease by A. Cedars
176 Surgical considerations for the explantation of the Parachute

left ventricular partitioning device and the implantation of the
HeartMate II left ventricular assist device by Y. Ravi et al
178 Intracranial aneurysm and sildenal by A. Adiga et al
181 Infective endocarditis caused by Klebsiella oxytoca in an intravenous
drug user with cancer by A. Mohamed et al
183 Rapidly enlarging neck mass in a neonate causing airway
compromise by K. Schmidt et al
185 Serendipitous discovery of peritoneal mesothelioma by A. Jaster and
J. Wachsmann
188 Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema
in Pneumocystis jiroveci pneumonia in AIDS by N. Saleem et al
191 Multiple dural-based hemangiopericytomas by E. Stroberg et al
194 Colorectal cancer implant in an external hemorrhoidal skin tag
by L. Liasis and H. T. Papaconstantinou
196 Bilateral synchronous plasmacytoma of the testis by G. Narayanan et al
198 Presentation of epidermolytic acanthomas as multiple tan papules on
the vulva by J. W. Fletcher et al
200 Rumpel-Leede phenomenon presenting as a hypertensive
urgency by D. Varela et al
202 Arm pain and erythema by B. M. Barth and A. L. Juergens
204 Rheumatoid meningitis associated with iniximab by S. Seago et al
207 Cryptococcal meningitis in a patient with sarcoidosis by T. N. Adams
and M. Gibson
209 Thyroid hormone resistance and its management by A. M. Rivas et al
212 The price of a 15-year delay in diagnosis of Sheehans syndrome
by R. Parikh et al
214 Linezolid-induced serotonin toxicity in a patient not taking monoamine
oxidase inhibitors or serotonin receptor antagonists by J. Sutton et al
Editorial and Book Review
220 On John Keats and Blue Zones by J. D. Cantwell
224 Book review: In Vitro Fertilization Comes to America by S. P. Marynick
From the Editor
230 Facts and ideas from anywhere by W. C. Roberts
Miscellany
118 Clinical research studies enrolling patients
164 In memoriam
187 Avocations: Photograph by R. Solis
216 Baylor news
226 Reader comments: Hearts considered for transplantation and
takotsubo syndrome by J. E. Madias, S. Y-Hassan, author reply by
Y. Ravi; Electronic medical records by L. Hughes; Facts and ideas by
T. Gore, J. Woods; Cuba by S. P. Marynick
238 2015 publications of the Baylor Scott & White Health North Division
medical and scientic staff
259 Instructions for authors
www.BaylorHealth.edu/Proceedings
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117
Clinical research studies enrolling patients through

Baylor Research Institute
Currently, Baylor Research Institute is conducting more than 800 research projects. Studies open to enrollment are listed in
the Table. To learn more about a study or to enroll patients, please call or e-mail the contact person listed.
Research area
Specific disease/condition
Contact information (name, phone number, and e-mail address)
Asthma and
pulmonary disease
Chronic obstructive pulmonary disease, asthma (adult)
Jana Holloway, RRT, CRC

Courtney Patenaude, BS
Horacio Martinez
214-818-9495
214-818-7899
214-820-0338
janahol@baylorhealth.edu
courtney.patenaude@baylorhealth.edu
horacio.martinez@baylorhealth.edu
Cancer
Breast, ovarian, endometrial, prostate, brain, lung, bladder, colorectal,

pancreatic, and head and neck cancer; hematological malignancies,
leukemia, multiple myeloma, non-Hodgkins lymphoma; melanoma
vaccine; bone marrow transplant
Grace Townsend
214-818-8472
cancer.trials@BaylorHealth.edu
Type 1 and type 2 diabetes, cardiovascular events
Lorie Estrada
214-820-3416
Lorie.estrada@baylorhealth.edu
Pancreatic islet cell transplantation for type I diabetics, who either have
or have not had a kidney transplant
Kerri Purcell, RN
817-922-4640
kerri.purcell@baylorhealth.edu
Type 2; cardiac events
Trista Bachand, RN
817-922-2587
trista.bachand@baylorhealth.edu
Pancreatic islet cell transplantation for type I diabetics, who either have or
have not had a kidney transplant; high cholesterol
Kerri Purcell, RN
817-922-4640
kerri.purcell@baylorhealth.edu
Diabetes (Dallas)
Diabetes (Fort Worth)
Gastroenterology
Heart and vascular

disease (Dallas)
Inflammatory bowel disease
Dr. Themistocles Dassopoulos
469-800-7180
T.Dassopoulos@baylorhealth.edu
Aortic aneurysms, coronary artery disease, hypertension, poor leg

circulation, heart attack, heart disease, congestive heart failure, angina,
carotid artery disease, familial hypercholesterolemia, renal denervation
for hypertension, diabetes in heart disease, cholesterol disorders, heart
valves, thoracotomy pain, stem cells, critical limb ischemia, cardiac
surgery associated with kidney injury, pulmonary hypertension
Merielle Boatman
214-820-2273
MeriellH@BaylorHealth.edu
Heart and lung transplant, mechanical assist device such as LVAD
Elizabeth Owens, BA, CCRP
214-820-4015
Liz.Owens@baylorhealth.edu
Heart and vascular disease

(Fort Worth)
Atrial fibrillation, atrial fibrillation post PCI
Meagan King
817-922-2583
Meagan.king@baylorhealth.edu
Heart and vascular disease

(Legacy Heart)
At risk for heart attack/stroke; previous heart attack/stroke/PAD; cholesterol

disorders; atrial fibrillation; overweight/obese; other heart-related conditions
Angela Germany
469-800-6409
lhcresearch@baylorhealth.edu
Heart and vascular

disease (Plano)
Aortic aneurysm; coronary artery disease; renal stent for uncontrolled

hypertension; poor leg circulation; heart attack; heart disease; heart valve
repair and replacement; critical limb ischemia; repair of aortic dissections
with endografts; surgical leak repair; atrial fibrillation; heart rhythm
disorders; carotid artery disease; congestive heart failure; gene profiling
Tina Worley
469-814-4712
christina.worley1@baylorhealth.edu
Hepatology
Infectious disease
Nephrology
Neurology
Liver disease
Jonnie Edwards
214-820-6243
jonnie.edwards@baylorhealth.edu
HIV/AIDS
Bryan King, LVN
214-823-2533
bryan.king@ntidc.org
Hepatitis C, hepatitis B
Jonnie Edwards
214-820-6243
Jonnie.edwards@baylorhealth.edu
Type 2 diabetes with chronic kidney disease
Lisa Mamo, RN
Dr. Harold Szerlip
214-818-2526
214-358-2300
Lisa.Mamo@BaylorHealth.edu
Harold.Szerlip@baylorhealth.edu
Stroke, migraine
Quynh Lan Doan
214-818-2522
quynh.doan@BaylorHealth.edu
Multiple sclerosis, stroke
Portland Pleasant, RN
214-820-7903
portland.pleasant@baylorhealth.edu
Cerebral aneurysms
Kennith Layton, MD
214-827-1600
KennithL@BaylorHealth.edu
Interventional stroke therapy
Tomica Harrison
214-820-2615
tomica.harrison@baylorhealth.edu
Rheumatology (9900 N.
Central Expressway)
Rheumatoid arthritis, psoriatic arthritis, lupus, gout,

ankylosing spondylitis
Giselle Huet
214-987-1253
ruth.huet@baylorhealth.edu
Surgery
Chronic limb ischemia, pain management with chest tubes, colon polyps,
diaphragm stimulators, and surgery as it pertains to GERD, breast cancer,
esophagus, colon, colon cancer, pancreas, lung, hernias, dialysis access,
per-oral endoscopic myology (POEM), thoracic outlet syndrome
Tammy Fisher
214-820-7221
tammyfi@BaylorHealth.edu
Bone marrow, blood stem cells
Grace Townsend
Gabrielle Ethington
214-818-8472
214-818-8326
Grace.Townsend@BaylorHealth.edu
gabriele@baylorhealth.edu
Solid organs
Jonnie Edwards
214-820-6243
jonnie.edwards@baylorhealth.edu
Obesity
Lorie Estrada
214-820-3416
Lorie.estrada@baylorhealth.edu
Neurosurgery
Transplantation
Weight management
Baylor Research Institute is dedicated to providing the support and tools needed for successful clinical research. To learn
more about Baylor Research Institute, please contact Kristine Hughes at 214-820-7556 or Kristine.Hughes@BaylorHealth.edu.
118
Proc (Bayl Univ Med Cent) 2016;29(2):118
The characteristics of Mohs surgery performed by

preceptorships
Howard. K. Steinman, MD, Henry Clever, MD, and Anthony Dixon, PhD, MBBS
Little is known about the practice characteristics of Mohs surgery performed by physicians who learned the procedure during their dermatology
residency training or through postresidency courses and observational
preceptorships. All published reports have investigated Mohs surgeons
trained in postresidency fellowships. This report presents the results of a
multicenter prospective cohort study evaluating 1834 consecutive Mohs
surgery cases performed during the same 6-month period by 9 Mohs
surgeons who learned the technique in residency or in postresidency
courses and observational preceptorships. One major complication was
reported, a hematoma requiring outpatient drainage in an emergency
room. There were 54 (2.9%) short-term complications, including 20
(1.1%) infections, 17 (0.9%) wound dehiscences, 9 (0.5%) cases of
skin flap necrosis, and 8 (0.4%) hematomas or postoperative bleeding episodes. These complication rates and the data evaluating tumor
type, anatomic location, primary vs. recurrent tumor status, tumor size,
postoperative wound size, number of Mohs surgery stages, and repair
type compare favorably to previously published reports.
ohs micrographic surgery (MMS) is a widely practiced skin cancer treatment that is safe, tissue sparing, eective, and economical (111). All published
reports supporting these conclusions evaluated Mohs
surgeons trained in postresidency fellowships. Many physicians
receive their MMS training outside of postresidency fellowships
(3). No published studies could be found assessing the practice
characteristics of MMS performed by nonfellowship-trained
Mohs surgeons. This study reports the results of a 6-month
prospective cohort study of 1834 consecutive MMS cases performed by 9 nonfellowship-trained Mohs surgeons at nine
locations. The practice characteristics of these Mohs surgeons
are analyzed and compared with previously published reports.
METHODS
Study approval was obtained from the Scott & White institutional review board and exempted from further oversight.
STROBE guidelines for patient series were adhered to. Nine
nonfellowship-trained Mohs surgeons with diering methods
of MMS training and levels of experience volunteered to submit
all cases they performed between August 1, 2012, and January
31, 2013. No cases were excluded. They received MMS training
in residency, postresidency courses followed by observational

preceptorships, or postresidency courses alone.
Each Mohs surgeon provided his or her date of birth, gender,
residency completion year, MMS training method, practice setting, geographic location, years of MMS experience, and total
number of MMS cases performed. Cases performed in residency
and before course and preceptorship training were excluded.
Each Mohs surgeon submitted a case log documenting tumor type, anatomic location, primary vs. recurrent tumor status,
tumor size, postoperative wound size, number of MMS stages,
and repair type. All identiable patient data were removed, and
the institutional review board required no study consent forms.
Participants reported all major complications, dened as adverse
events requiring an emergency room visit or hospital admission within 48 hours of the procedure. All short-term, minor
postoperative complications were reported, including wound
infections (dened as a postoperative wound the Mohs surgeon
felt required oral antibiotic therapy), wound dehiscence (partial
or complete), bleeding, hematoma, seroma, and ap necrosis.
Participants were not asked to track long-term adverse sequelae,
including scars requiring revision, permanent sensory or motor
nerve damage, or tumor recurrence.
RESULTS
Nine dermatologists with dierent forms of MMS training and levels of experience submitted 1834 MMS cases. Six
(66%) received their training in residency, 2 (22%) through
courses followed by observational preceptorships, and 1 (11%)
from course training alone. Ages ranged from 38 to 64 years
(average, 52 years). Eight were male and one was female. All
were board-certied dermatologists practicing in the United
States: three (38%) from the Midwest, three (38%) from the
Southwest, two (25%) from the West, and one (13%) from
the Southeast. Participants completed their MMS training an
From Texas A&M Health Science Center College of Medicine and DermOne
Dermatology Clinics, Irving, Texas (Steinman); First Capitol Dermatology, St.
Charles, Missouri (Clever); and Australasian College of Cutaneous Oncology,
Victoria, Australia (Dixon).
Corresponding author: Howard K. Steinman, MD, Chief of Mohs Surgery and
Dermatologic Surgery, DermOne Dermatology Clinics, 2021 N. MacArthur Blvd.,
Suite 300, Irving, TX 75056 (e-mail: hksteinman@gmail.com).
119
Table 1. The training method, practice setting, career and case experience, and number and percentage of cases submitted by each
Mohs surgeon
Surgeon
Training
method*
Practice setting
Career
cases
Career experience
(years)
Cases submitted
(n = 1834)
Percent of
cases
Solo practice
>5000
20
97
5.3%
Academic group
>5000
20
54
3.0%
CP
Solo practice
10002500
311
16.9%
Dermatology group
>5000
16
328
17.9%
CP
Solo practice
>5000
394
21.5%
Multispecialty group
5001000
147
8.0%
Solo practice
5001000
12
129
7.0%
Solo practice
>5000
300
16.3%
Solo practice
250500
15
Practice setting
74
4.0%
1305
71%
Dermatology group (11%)
328
18%
Multispecialty group (11%)
147
8%
University/academic (11%)
54
3%
Solo practice (67%)
Career case experience
>5000
1173
64%
10002500
311
17%
5001000
276
15%
250500
74
4%
*CP indicates course followed by preceptorship; C, Course; R, Residency.
average of 11.6 years (range, 220 years) before the onset of the
study. The training method, practice setting, career experience,
and number and percentage of cases submitted by each Mohs
surgeon are shown in Table 1.
Of the 1834 tumors treated, 1207 (65.8%) were basal cell
carcinoma, 503 (27.4%) were squamous cell carcinoma, and
116 (6.3%) were squamous cell carcinoma in situ. Thirteen
(0.7%) basosquamous cell carcinomas were categorized as
squamous cell carcinomas. Four tumors (0.2%) were atypical broxanthomas, and four (0.2%) were other rare tumors.
None of the participants treated melanocytic tumors with
MMS. Overall, 96.4% of tumors were primary and 3.6%
were recurrent.
In terms of location, 1509 (82.2%) tumors were located on
the face, 100 (5.5%) on the scalp, 82 (4.5%) on the extremities,
58 (3.2%) on the neck, 42 (2.3%) on the trunk, 40 (2.2%) on
the hands, and 3 (0.2%) on the feet. The mean tumor size was
1.22 cm (standard deviation [SD] 1.71 cm), with a median
of 0.8 cm. The mean nal wound size was 3.77 cm (SD 5.68
cm) with a median of 2.25 cm. The average number of MMS
stages to obtain clear margins was 1.66 (SD 0.82); 909 (49.6%)
cases were cleared after 1 stage, 718 (39.1%) after 2 stages, 140
(7.6%) after 3 stages, 49 (2.7%) after 4 stages, and 18 (0.9%)
after 5 or more stages.
Of the surgical defects, 1029 (56.1%) were repaired linearly,
512 (27.9%) with local cutaneous aps, 123 (6.7%) by secondary intention, 85 (4.6%) with skin grafts, 6 (0.3%) with partial
repairs, 6 (0.3%) with a combination of techniques, and 1 with
120
a porcine xenograft. A total of 72 cases (3.9%) were referred to

other surgeons for repair.
Fifty-ve (3.0%) adverse events were reported. One (0.05%)
major complication was reported in a patient with a hematoma
requiring drainage in an emergency room. The 54 (2.9%) shortterm complications included 20 (1.1%) infections, 17 (0.9%)
wound dehiscences, 9 (0.5%) cases of skin ap necrosis, and 8
(0.4%) hematomas or bleeding episodes. The anatomic distribution of infections was face (70%), scalp (15%), neck (5%),
and extremities (15%); 86% of the wound dehiscences were
on the head or neck.
DISCUSSION
Physicians receive various forms of MMS training (3). Previously published MMS case series evaluated only fellowshiptrained Mohs surgeons. To our knowledge, this is the rst report
assessing nonfellowship-trained Mohs surgeons.
Our study involved 1834 cases from 9 nonfellowshiptrained Mohs surgeons from the same 6-month period. Merritt
et al (2) studied 1792 cases from 13 fellowship-trained Mohs
surgeons with the same general design and scope. Alam et al
(1) conducted a comprehensive study of 20,821 cases from
36 Mohs surgeons, focusing primarily on adverse eects. Recurrence rates were not evaluated in any of these studies, as
5-year follow-up data are considered the minimum duration
necessary for accurate recurrence assessment (12, 13). All three
studies were conducted before current MMS appropriate use
criteria were published (14). Thus, clinical data permitting a
Volume 29, Number 2
Table 2. Tumors treated with Mohs surgery: study data versus

previous reports
Table 4. Number of Mohs surgery stages to obtain clear margins:

study data vs. previous reports
Tumor types
First author, year (ref)
BCC
SCC
SCCis
6.3%
Number of Mohs surgery stages

Other
Total cases
0.4%
1834
7.5%
400
>5
Average
Study data
50%
39%
7.6% 2.7% 0.9%
1.7
Cook, 1998 (20)
67%
23%
4.0% 3.5% 3.0%
1.5
Study data
66%
27%
Cook, 1998 (20)
77%
16%
Cook, 2003 (9)
68%
29%
1343
Kimyai-Asadi, 2005* (7)
1.7
Bialy, 2004 (21)
68%
32%
98
Casey, 2009* (8)
1.8
Kimyai-Asadi, 2005 (7)
72%
21%
6.7%
3937
Alam, 2010 (22)
Casey, 2009 (8)
76%
22%
2.0%
Alam, 2010 (22)
73%
27%
Martin, 2010 (15)
64%
28%
8.0%
Merritt, 2012 (2)
61%
31%
8.3%
1792
Alam, 2013 (1)
63%
35%
2.4%
20,821
42%
41%
12%
4.0% 1.8%
1.9
N/A
Martin, 2010* (15)
1.4
2000
Rogers, 2010* (16)
1.4
950
Merritt, 2012* (2)
1.6
Lilly, 2012* (19)
1.3
* Only average of total stages reported.
BCC indicates basal cell carcinoma; SCC, squamous cell carcinoma; SCCis, squamous
cell carcinoma in situ.
determination of whether study cases complied with these criteria were not obtained.
Of the 9 Mohs surgeons evaluated, 6 (55%) were in solo
practice and 1 each (11%) were in academic, dermatology group,
and multispecialty group practices (Table 1). Campbell (13) surveyed 303 fellowship-trained Mohs surgeons and reported a
distribution of 30% in solo practice, 21% in academic practice,
39% in dermatology group practice, 9% in multispecialty group
practice, and 1% listed as other. The dierences in practice
setting distribution may reect a sampling bias or that more
nonfellowship-trained Mohs surgeons are in solo practice.
The percentage and distribution of tumor types treated in
this study is very similar to that of previous reports (Table 2) (1,
2, 79, 15, 2022). Fewer recurrent tumors (4%) were treated
than in previous reports. Ravitskiy et al (11) reported on 379
tumors and found that 10% were recurrent. Cook and Zitelli
(20) analyzed 400 consecutive cases and found that 16% were
recurrent. These dierences possibly suggest that nonfellowship-trained Mohs surgeons receive fewer outside referrals for
treatment of recurrent cancers. This study data showed a low
percentage of tumors (0.4%) that were not basal cell carcinoma,
squamous cell carcinoma, or squamous cell carcinoma in situ.
Other studies have reported ranges of 2% to 8% of rarer tumor
types (Table 2). This may indicate that fellowship-trained Mohs
surgeons are more prepared to manage rarer tumor types with
MMS. The anatomic distribution of tumors treated in the study
is also similar to that of previously published series (Table 3) (2,
7, 8, 16, 19, 20, 22).
The average number of MMS stages required to achieve
tumor clearance was 1.66. This value and the distribution of
required stages is very similar to previous reports (Table 4) (2, 7,
8, 15, 16, 19, 20, 22). This study's mean preoperative tumor size
of 1.2 cm2 is similar to that reported by Kimyai-Asadi (1.0 cm2)
(7) and Merritt (1.1 cm2) (2). The average postoperative wound
size (3.8 cm2) was between the values reported by Kimyai-Asadi
Table 3. Anatomic distribution of tumors treated with Mohs surgery: study data versus previous reports
Face
Scalp
Neck
Study data
82%
5.5%
3.2%
Cook, 1998 (20)

Kimyai-Asadi, 2005*
87%
76%
5.6%
3.7%
Casey, 2009* (8)
83%
4.5%
3.4%
Alam, 2010* (22)
80%
5.4%
2.2%
68%
7.0%
4.0%
Rogers, 2010*
(7)
(16)
Merritt, 2012* (2)
Head &
neck
Ext.
2.3%
4.5%
Trunk &
ext.
Ext. &
genitalia
3.6%
Genitalia
Other
2.4%
5.5%
7.6%
1.8%
8.0%
86%
Hands &
feet
8.0%
4.8%
73%
Lilly, 2012 (19)
Trunk
0.2%
2.0%
7.5%
9.3%
17%
8.0%
10%
4.0%
10%
1.0%
3.0%
0.2%
Ext. indicates extremities.

*Data for some anatomic areas combined.
20002006 data only.
April 2016
The characteristics of Mohs surgery performed by nonfellowship-trained dermatologists
121
Table 5. Surgical repair methods after Mohs surgery: study data versus previous reports
Surgical repair methods
2nd intention
Linear
Flaps
Graft
Referred
Study data
6.7%
56.1%
Futoryan, 1995 (18)
3.4%
53.0%
27.9%
4.6%
3.9%
26.0%
17.0%
Other
Number of cases
0.6%
1834
0.1%
530
Cook, 1998 (20)
39.0%
37.0%
10.0%
13.0%
Kimyai-Asadi, 2005 (7)
11.0%
69.0%
14.0%
6.2%
6.8%
53.0%
27.0%
14.0%
Casey, 2009 (8)
18.0%
44.0%
19.0%
9.0%
10.0%
N/A
Alam, 2010 (22)
10.0%
50.0%
21.0%
8.7%
10.3%
20,821
Martin, 2010 (15)
3.0%
62.0%
18.0%
7.0%
6.0%
Maragh, 2008* (17)
0.8%
0.4%
400
3937
1115
Rogers, 2010 (16)
10.0%
74.0%
13.0%
2.9%
Merritt, 2012 (2)
18.0%
54.0%
9.3%
12%
6.5%
Lilly, 2012 (19)
6.4%
65.0%
14.0%
6.1%
5.7%
4.0%
950
0.7%
1204
1792
2.3%
670
*Includes 32 cases treated with slow-Mohs (permanent section margin control) for melanoma in situ.
Includes 0.7% that were porcine xenografts.
(7) (4.3 cm2) and Merritt (2) (1.9 cm2) and similar to other
reports (15, 19). The types and distribution of wound repairs
are summarized in Table 5 and are in line with the results of
multiple previous reports (2, 7, 8, 1520, 22).
Of the cases reported, 116 (6.3%) were squamous cell
carcinoma in situ. The authors could nd no other prospective
multicenter cohort MMS studies distinguishing squamous
cell carcinoma in situ from other tumor types treated. Of
these, 97% were primary tumors, 80% were on the face or
scalp, and 9% were on the extremities. Leibovitch et al (23)
reported a 9-year prospective multicenter case series of all
squamous cell carcinoma in situ treated with MMS. Of 270
cases, 49.2% were primary and 93.4% were on the head and
neck. Chuang et al (24) reported a single center prospective
study of consecutive squamous cell carcinoma in situ tumors
treated with MMS. Of 29 cases, 79.3% were on the head and

neck and 20.6% were on the extremities. Unlike squamous
cell carcinoma and basal cell carcinoma, it is generally recognized that squamous cell carcinoma in situ can often be
managed by surgical and nonsurgical modalities other than
MMS (25).
Several MMS studies have focused on the frequency of adverse events (1, 2, 4, 9, 1519). This study's results compare
favorably with those of previous reports (Table 6). The study's
one major complication is comparable to previous reports (1, 2,
7). The study's low infection rate (1.1%) is in line with previous
series (Table 6) (4, 9, 15, 1719). The anatomic distribution of
infections of face (70%), scalp (15%), neck (5%) and extremities (15%) is similar to other large series (1618). Tumors >2.1
cm in diameter had a higher infection rate than lesions <1.25 cm
Table 6. Complication rates associated with Mohs surgery: study data versus previous reports
Complications
First author, date (ref)
Hematoma
Bleeding
Study data
Hematoma/
bleeding
Necrosis
Infection
Dehiscence
0.40%
0.50%
1.10%
0.93%
Futoryan, 1995 (18)

Cook, 2003 (9)
Impaired
healing
1834
2.45%
0.50%
0.15%
0.82%
Maragh, 2008* (17)
0.07%
Number of cases
530
0.10%
1343
0.07%
1115
Martin, 2010 (15)
0.90%
950
Rogers, 2010 (16)
0.91%
1204
Merritt, 2012 (2)
0.17%
1.23%
0.29%
0.94%
0.33%
1792
Elliott, 2012 (4)
0.21%
954
Lilly, 2012 (19)
1.49%
670
Alam, 2013 (1)
0.10%
0.40%
0.14%
20,821
*Mohs surgery and slow-Mohs (permanent section margin control) procedures.
122
Volume 29, Number 2
(P = 0.01). Merritt (2) reported a greater overall complication

rate (not only infections) for tumors >1.6 cm vs. 1.12 cm (P =
0.0001). A nonsignicant trend in increased wound infections
in this study was noted with increasing number of MMS stages
performed from 2 through 4 stages, yet no cases requiring 5
stages developed infections. This may be due to a small sample
size of 17 of 1834 cases (0.9%) requiring ve or more stages.
No data were collected on the use of prophylactic postoperative
antibiotics, which might have been used more frequently with
tumors requiring 5 MMS stages. The overall dehiscence rate
of 0.93% was higher than that reported by Cook (0.10%) (9)
and Merritt (0.33%) (2).
Limitations in the study include the fact that only 9 Mohs
surgeons were evaluated, there was a gender bias with eight
males and one female, and there was a bias towards participants
in private solo practice. A disproportionate number of cases
was submitted by Mohs surgeons with >5000 cases of career
experience, and the number of cases submitted by participants
varied signicantly. Compliance with appropriate use criteria
was not assessed. The determination of an infection was left to
each surgeon's clinical assessment without the requirement of
bacterial culture conrmation.
Acknowledgments
The authors wish to thank the following individuals for their
contributions to this study: Robert Aylesworth, David Butler,
Igor Chaplik, Carlos Garcia, John Hamill, Alex Miller, Joseph
Schneider, Shannon Setzer, Juhee Song, Donald Tillman, and
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The characteristics of Mohs surgery performed by nonfellowship-trained dermatologists
123
Virtual reality and brain computer interface in

neurorehabilitation
David B. Salisbury, PsyD, ABPP, Marie Dahdah, PhD, Simon Driver, PhD, Thomas D. Parsons, PhD, and
Kathleen M. Richter, MBA, MS
The potential benefit of technology to enhance recovery after central nervous system injuries is an area of increasing interest and exploration. The
primary emphasis to date has been motor recovery/augmentation and
communication. This paper introduces two original studies to demonstrate
how advanced technology may be integrated into subacute rehabilitation.
The first study addresses the feasibility of brain computer interface with
patients on an inpatient spinal cord injury unit. The second study explores
the validity of two virtual environments with acquired brain injury as part
of an intensive outpatient neurorehabilitation program. These preliminary
studies support the feasibility of advanced technologies in the subacute
stage of neurorehabilitation. These modalities were well tolerated by participants and could be incorporated into patients inpatient and outpatient
rehabilitation regimens without schedule disruptions. This paper expands
the limited literature base regarding the use of advanced technologies
in the early stages of recovery for neurorehabilitation populations and
speaks favorably to the potential integration of brain computer interface
and virtual reality technologies as part of a multidisciplinary treatment
program.
he yearly incidence of traumatic brain injury (TBI) (1.7

million), acquired brain injury (900,000), and spinal
cord injury (SCI) (12,000) in the US fails to adequately
reect the long-term impact and annual societal cost,
which may exceed $100 billion a year (15). As advances in
medical care are improving survival rates in these populations,
the need for a multidisciplinary approach focusing on long-term
outcomes, secondary complications, and quality of life is magnied (3, 6). This multidisciplinary approach strongly aligns with
key aspects of the World Health Organizations International
Classication of Functioning, Disability, and Health Model,
where the primary health conditions must be conceptualized in
relation to environmental and contextual factors with emphasis
upon improving function (7) (Figure 1). Advanced technologies such as brain computer interface (BCI), which uses brain
patterns to help patients bypass injuries that impede motor or
verbal responses, and virtual reality (VR) have shown potential
as viable treatment tools in the rehabilitation setting (811);
however, the application of advanced technologies in neurorehabilitation is not systematic, and studies to support their use
in clinical settings remain limited (1214). This prompted our
124
Figure 1. The International Classification of Functioning, Disability, and Health

model. Source: World Health Organization (7).
group to begin exploratory studies into the feasibility and utility

of o-the-shelf BCI and VR technologies with neurorehabilitation populations. This paper introduces two original studies to
demonstrate how advanced technology may be integrated into
the subacute phase of central nervous system recovery. Approval
to complete the studies was obtained from the hospitals institutional review board.
FEASIBILITY STUDY AND PILOT STUDY
On the SCI rehabilitation treatment unit at the Baylor Institute for Rehabilitation, 25 medically stable patients without
severe cognitive or psychiatric impairment were included in
the rst study. Most participants had sustained cervical-level
(48%) or thoracic-level (44%) SCIs and had residual tetraplegia
(52%). At initial contact, an extensive screening was completed, including neuropsychological tests, formal questionnaires of
mood, pain, and physical status, and qualitative, study-specic
questions. Select measures were repeated immediately before
the o-the-shelf BCI paradigm and at the nal contact. The
From the Baylor Institute for Rehabilitation, Dallas, Texas (Salisbury, Dahdah,
Driver); Baylor Regional Medical Center at Plano, Plano, Texas (Dahdah); the
Department of Psychology, the University of North Texas, Denton, Texas (Parsons);
and the Center for Clinical Effectiveness, Baylor Scott & White Health, Dallas,
Texas (Richter).
Corresponding author: David B. Salisbury, PsyD, ABPP, Department of
Neuropsychology, Director of Clinical Training, Baylor Institute for Rehabilitation,
411 N. Washington Avenue, Dallas, TX 75246 (e-mail: dsalisbury@bir-rehab.
com).
BCI paradigm involved a cube rotation task using the EPOC

headset (Emotiv, San Francisco, CA). This device was originally developed for gaming, but has been increasingly used
in research studies (1517). Although this o-the shelf BCI
is less sensitive in its capture of electroencephalographic data
when compared with traditional medical devices (18), its portability, ease of use, and cost made it an attractive option for
an inpatient hospital setting. This device allows for wireless
14-channel electroencephalographic recording based on the
international 10 to 20 locations (AF3, F7, F3, FC5, T7, P7,
O1, O2, P8, T8, FC6, F4, F8, AF4) along with two reference
electrodes (P3, P4).
After a brief training session for each increasingly complex
BCI task (push cube, move left, move right, and cube disappearance), each participant performed three trials, lasting 8
seconds each. A MATLAB scoring program was employed for
data acquisition, to log stimulus presentation, and for psychophysiological monitoring (19). The results of the feasibility
study suggested that the technology was easily learned (92%
of trials were successful) and mastery of the paradigm was not
signicantly related to prior technology prociency, current
cognitive functioning, pain level, or emotional distress. Equally
important, the participants enjoyed the experience and had
no reported adverse eects from the headset. The encouraging
ndings of the small feasibility study open the door for future
work among inpatient SCI populations during rehabilitation.
This is an ideal time to provide initial exposure and training
for such technology if clinical paradigms can be developed.
The daunting next step entails the development of paradigms
specic to SCI treatment targets.
On our SCI treatment team, key psychological treatment
goals revolve around psychological adjustment, pain management, and educational interventions that often incorporate aspects of social skills training. Future use of BCI paradigms will
be dependent on the ability to integrate VR paradigms that are
linked to this triad of clinical priorities. Of particular interest
within the rehabilitation psychology eld is programming based
on frequent challenges and emotionally laden scenarios after
SCI. These scenarios could touch upon addressing disability
with family/friends, navigating public areas with limited access, and addressing intimacy concerns. One could envision a
preventive approach using virtual social simulations to promote
more adaptive skills in early stages of rehabilitation. BCI could
also be linked to biofeedback-like paradigms to further address
pain, anxiety, and emotional regulation, which can complicate
outcomes after SCI.
The emphasis on clinically relevant and generalizable treatment environments may be in part addressed via immersive
environments. A second pilot study was conducted to validate
the cognitive rehabilitation ecacy of two virtual environments
following central nervous system insult. Participants included
individuals with acquired TBI, stroke, brain neoplasm, and anoxic injury. A key focus was treatment outcomes associated with
VR training of specic executive functions: cognitive exibility,
working memory, complex attentional processes, and cognitive
and motor inhibition, in addition to processing speed.
April 2016
Individuals who consented to participate in this study were

enrolled in a multidisciplinary outpatient day neurorehabilitation program at the Baylor Institute for Rehabilitation. The
only deviation in programming was the introduction of the
two VR programs as a supplementary cognitive rehabilitation
intervention. The laptop-presented virtual apartment (ClinicaVR: Apartment Stroop [20]) and virtual classroom settings
(VR Classroom [2124]) were selected because they simulate
demands and distractions found in real-world settings. While
in the immersive environments, participants performed two
conditions of a response inhibition task in the face of distractions. Task diculty increased across sessions with respect to the
quantity and type of distractions the participant was exposed to,
with a total of 8 training sessions completed biweekly (4-week
treatment duration). A Z800 3DVisor head-mounted display
(HMD) was used to create a 3D-like eect, and the built in
3-axis head-tracker allowed patients to look 360 degrees around
themselves by turning their head.
During baseline testing (session 1) and the nal session (session 8), patients were additionally administered the Automated
Neuropsychological Assessment Metrics Stroop and Go-No
Go computerized tests, Woodcock-Johnson 3rd Edition Pair
Cancellation subtest, and Delis-Kaplan Executive Functions
System Color-Word Interference test (2527). These tests were
used to compare VR treatment outcomes with performance
on unimodal Stroop/executive testing and paper-pencil tests.
Patients also completed the Simulator Sickness Questionnaire
upon conclusion of sessions 1 and 8 to document any symptoms
associated with the HMD.
Twenty-one brain injury patients participated in the pilot study: 9 diagnosed with stroke (43%), 6 with TBI (29%),
2 with anoxic injury (10%), 3 with brain tumor (14%), and
1 with amyloid angiopathy (5%). Preliminary analyses were
conducted using the performance of the group with stroke,
which accounted for the largest diagnostic category. The smaller
groups comprising patients with anoxic injury and brain tumor
demonstrated such profound variability that a combined analysis would have been minimally informative. When comparing
the stroke subgroup with 9 demographically matched healthy
controls on the ClinicaVR: Apartment Stroop, there were no
signicant group dierences in reaction time on conditions with
distractions (F(1,16) 3.418, P = 0.062) or without distractions
(F(1,16) 1.793, P = 0.200) employing analysis of covariance
and adjusting for age. However, response time was signicantly
slower for stroke patients than for controls (F(1,16) 17.109, P <
.01). The former may be due to the fact that the stroke subgroup
included some relatively young patients, ranging in age from 22
to 65 (mean age = 47). It may also be that the stroke group was
relatively higher functioning cognitively, given that patients with
signicantly impaired comprehension, bimanual apraxia, and
attention (e.g., patients with attention span < 10 minutes) that
could potentially confound cognitive performance outcomes on
the VR programs were excluded from the study. However, two
of the stroke patients were noted to respond with errors on all
items of the incongruent word-color stimulus trial of the Stroop
task, indicating variation in severity level within this group.
Virtual reality and brain computer interface in neurorehabilitation
125
Qualitatively, across all acquired brain injury patient groups

treated in this pilot study (TBI, stroke, anoxic injury, etc.),
those exhibiting overt impulsivity or anxiety appeared to exhibit
impulsive responding on the VR-based executive measures. Patients with reported or observable fatigue demonstrated reduced
attention and self-monitoring, committing omission errors due
to uctuations in engagement. As additional quantitative error
analysis is completed, it will be interesting to learn whether
results parallel qualitative observations.
Six of the 21 patients initially endorsed slight or moderate
fatigue, headache, eye strain, diculty focusing, perspiring,
and blurred vision on the Simulator Sickness Questionnaire,
which assesses the occurrence, nature, and severity of sickness symptoms induced by virtual environments (28). By the
fourth session, the number of patients reporting HMD-related
symptoms declined to four. No adverse events occurred, and
no patients volitionally withdrew from the study. Six of the 21
patients partially completed the study, but failed to complete all
8 intervention sessions. Two patients were medically withdrawn
from the day neurorehabilitation program due to refractory
medical complications, two patients self-discharged from the
program against medical advice, and four patients rehabilitation
regimens were concluded prior to their projected discharge dates
when insurance or state-assisted benets were not extended.
With regard to feasibility, similar to the BCI apparatus described above, the portability, ease of use, and cost of the devices
used to administer the VR programs made them amenable to
this setting. Scheduling of the VR intervention sessions and
space required constant and eective communication between
the research team and the day neurorehabilitation teams, due
to the variability in patient schedules, modications in length
of stay, and unplanned events (e.g., illness, external medical
appointments, impact of payer source on rehabilitation days).
The day neurorehabilitation team was positively responsive to
integration of the VR intervention in the rehabilitation program. Due to built-in demonstrations paired with verbal instructions from the research team members administering the
VR interventions, patients found the technology user-friendly.
Some patients provided unsolicited feedback, stating that the
virtual environments and internal distractions in the programs
were realistic. In fact, patients spontaneously commented on the
improvement in their performance from initial to later sessions.
One patient specically attributed an observable subjective improvement in reaction time to the VR intervention.
The eorts to replicate home and school settings using VR
in the pilot study allow for potentially highly relevant information to guide discharge planning. It is hoped that ndings from
this pilot study will encourage ongoing study to validate VR
technologies in neurological populations for the purpose of
enhancing cognitive intervention and rehabilitation.
lack of adverse eects even with patients in the subacute stage

of recovery, were quite encouraging. Still, the clear enthusiasm
for technology must be tempered by an acknowledgment of
potential barriers. The key concerns involve issues surrounding
the utility of BCI and VR, management of technological problems, and nancial feasibility. The virtual environments used in
these pilot studies are not commercially available, and only a
few research labs have access to them. Further, a number of VR
systems use arrays of screens to allow for full-body interactions,
costing many thousands of dollars. From a utility standpoint,
our projects ranged from simple visual stimuli to more advanced
depictions of real-world settings. Still, there may be a need for
more realistic visual paradigms. Studies are needed to assess
the impact and potential clinical ecacy of varying levels of
stimulus delity and immersion.
Our studies involved collaboration with experts in the area
of technology and psychology who could provide any needed
assistance in a timely manner. The presence of an information
technology support sta was also readily available as part of our
hospital system. Still, occasions arose where technology did not
work properly, resulting in delayed intervention or the need
to reschedule. Such complications speak to the challenges of
implementing interventions dependent upon technology within
inpatient and outpatient rehabilitation settings. Any delays in
these fast-paced settings, requiring the coordination of various
disciplines, can be quite disruptive to the milieu.
Finally, the nancial feasibility of VR and BCI will largely be
determined by future outcomes research. Unless there is support
for clinical gain in the form of improved outcomes, decreased
complications, or secondary decline in medical costs (e.g., decreased length of stay, less use of future medical services), cost
concerns may prohibit adoption of such technologies. Mainstream implementation in rehabilitation would be a nancial
challenge considering the trend of declining reimbursement for
clinical services and emphasis on bundled services with recent
health care changes. The initial cost must be coupled with the
need for sta training and statistician support by individuals
trained to analyze the data formats associated with this technology. Additionally, BCI and VR require a private space that limits
distractions that are all too frequent in rehabilitation settings.
Private rooms or dedicated areas for such interventions would be
ideal, yet allocation of such space was a challenge in our studies.
CHALLENGES IN TECHNOLOGY APPLICATION

The preliminary studies presented herein represent initial
attempts to explore the feasibility and potential benet of VR
and BCI technologies. The ease of training and positive participant response with VR and BCI paradigms, along with the
1.
126
Acknowledgments
The authors would like to thank Anne Carlew, BS, Erin Sullivan, MS, and Jesse Smotherman, BS, for their assistance with
data collection and the rehabilitation therapy teams of Baylor
Institute for Rehabilitations spinal cord team and day neurorehabilitation program for their coordination eorts. We greatly
appreciate Digital Media Works for use of its VR programs.
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Virtual reality and brain computer interface in neurorehabilitation
127
Safety and efficacy of packed red blood cell transfusions

at different doses in very low birth weight infants
Lea H. Mallett, PhD, Vinayak P. Govande, MD, Ashita Shetty, MD, and Madhava R. Beeram, MD
This double-blinded, randomized, crossover study evaluated the safety

and effectiveness of 20 mL/kg aliquots of packed red blood cell (PRBC)
transfusions versus 15 mL/kg aliquot transfusions in very low birth weight
(VLBW) infants with anemia. The study enrolled 22 hemodynamically
stable VLBW infants requiring PRBC transfusions, with a mean gestational
age of 25.7 2.2 weeks and birth weight of 804 261 g. Each infant
was randomized to receive one of two treatment sequences: 15 mL/kg
followed by 20 mL/kg or 20 mL/kg followed by 15 mL/kg. The infants
were monitored during and after transfusions, and the efficacy and safety
of the treatments were evaluated. Infants had higher posttransfusion
hemoglobin (13.2 g/dL vs 11.8 g/dL, P < 0.01) and hematocrit levels
(38.6 g/dL vs 34.4 g/dL, P < 0.01) following 20 mL/kg PRBC transfusions
when compared to 15 mL/kg transfusions. There were no differences
in the incidence of tachypnea, hepatomegaly, edema, hypoxia, necrotizing enterocolitis, or vital sign instability between groups. In conclusion,
high-volume PRBC transfusions (20 mL/kg) were associated with higher
posttransfusion hemoglobin and hematocrit levels but no adverse effects.
Higher-volume transfusions may reduce the need for multiple transfusions
and therefore the number of donors the infant is exposed to.
nnually, more than 60,000 infants are born in the

United States with a birth weight 1500 g. These very
low birth weight (VLBW) infants are at risk of serious complications, including anemia of prematurity.
Anemia of prematurity is caused by ineective hematopoiesis
and iatrogenic blood loss through frequent phlebotomy and
is exacerbated by low iron stores. Anemia leads to inadequate
oxygen delivery to tissues and poor growth. As a result, VLBW
infants are a heavily transfused population, accounting for nearly three-quarters of neonatal red blood cell transfusions (13).
Although blood transfusions are considered essential, there
are concerns related to infection risk, the safety of directed
donations, and refusal based on religious beliefs (4). Limiting
packed red blood cell (PRBC) transfusions may reduce transfusion-associated infection and iron overload (5). Transfusion
guidelines are based on expert opinion, rather than evidence,
and therefore vary among hospitals, with some units favoring
restrictive guidelines and others more liberal guidelines (68).
Although the traditional volume of PRBC transfusions ranges
from 10 to 20 mL/kg (9), there is still considerable debate
128
regarding the optimal volume of transfusion. In a systematic

review, only four trials, with 146 infants, compared transfusion
volumes of 10 versus 20 mL/kg (3). These studies showed no
dierences in neonatal outcomes, but the number of patients in
each study was small and markedly limited the power of these
studies to detect a dierence. The purpose of this study was
to evaluate the safety and eectiveness of using larger-volume
aliquots for PRBC transfusions in preterm VLBW infants.
METHODS
This study was conducted at McLane Childrens Hospital,
Baylor Scott & White Health, in Temple, Texas. VLBW infants
admitted to the neonatal intensive care unit that were expected
to require at least two PRBC transfusions after 48 hours of
life were eligible for enrollment. Patients with any of the following were excluded: birth weight <500 g, congenital heart
defects, or hemodynamic instability (dened as pulse >180
beats/min and capillary rell >3 sec). This was a randomized, double-blind, crossover study. Informed parental consent was obtained for eligible patients and then each infant
was randomized, using a random number generator, to one of
the two treatment sequences: 15 mL/kg transfusion followed
by 20 mL/kg transfusion or 20 mL/kg transfusion followed by
15 mL/kg transfusion. For both treatment groups, the blood
was transfused intravenously over 3 hours.
The blood product utilized for this study consisted of
component aliquot bags with a hematocrit of 60%, stored in
Nutricel AS-3 (Haemonetics, Pittsburgh, PA), which contains
dextrose, adenine, monobasic sodium phosphate, and sodium
chloride transfused via sterile tubing. All PRBC transfusions
were cytomegalovirus negative, leukocyte reduced, O-type with
the same Rh type as the infant.
Patients were enrolled over a 24-month period (January
2000December 2002). Clinical and demographic information,
including the Score for Neonatal Acute Physiology (SNAP-II),
From the Department of Pediatrics, McLane Childrens Hospital, Baylor Scott &
White Health/Texas A&M Health Science Center College of Medicine, Temple,
Texas.
Corresponding author: Lea H. Mallett, PhD, Department of Pediatrics, McLane
Childrens Hospital, Baylor Scott & White Health, 1901 SW H. K. Dodgen Loop,
Building 300, MS-CK-100, Temple, TX 76502 (e-mail: lmallett@sw.org).
was collected (10). The need for transfusion was based on current transfusion guidelines but ultimately determined by the
attending neonatologist. Before transfusion, the following specic parameters were assessed among both treatment groups:
1) respiratory distress employing the Silverman Score (11); 2)
presence of edema or hepatomegaly; and 3) vital signs (heart
rate, respiratory rate, blood pressure, and oxygen saturations).
Vital signs were monitored hourly during and up to 6 hours
after transfusion. Hematocrit, hemoglobin, and red blood cell
counts were also collected 1 hour before transfusion and for
3 hours after transfusion.
The primary outcome was posttransfusion change in hemoglobin and hematocrit in infants following both PRBC
transfusion treatment sequences. Secondary outcomes included
vital sign instability, edema or hepatomegaly, and respiratory
distress. Statistical analyses were performed using SAS Version
8.2 (SAS Institute, Cary, NC). All data were compared using
analysis of variance for a crossover design (12). The traditional
denition of a P value of 0.05 or less for statistical signicance
was applied (13).
Table 1. Demographic and clinical characteristics

by treatment group
Treatment sequence
15, 20 mL/kg
(n = 10)
20, 15 mL/kg
(n = 12)
Gestational age (wk, mean SD)
25.6 2.2
26.4 2.2
Birthweight (g, mean SD)
773 258
830 272
White
Black
Hispanic
Vaginal
Routine C-section
Emergency C-section
26 6
28 6
Mothers race or ethnic group
Delivery route
Maternal age (yr, mean SD)

Gravida
1
RESULTS
2
3
8
Twenty-four infants were enrolled in the study; 2 parents
3
2
3
withdrew consent prior to randomization, and the remain4
1
4+
ing 22 patients were randomized into one of the two treatment sequences: 15 mL/kg transfusion followed by 20 mL/kg
Prenatal care
10
12
transfusion or 20 mL/kg transfusion followed by 15 mL/kg
Antepartum complications
10
11
transfusion. Seven patients were discharged after receiving only
Arterial line
1
1
the rst transfusion and 15 patients received 2 transfusions.
Apgar scores (mean SD)
Demographic and clinical characteristics of study infants by
1 min
4.8 2.8
6.2 2.4
treatment group are presented in Table 1. The median number
5 min
7.9 1.3
8.1 1.3
of days between the rst and second transfusion for all patients
was 8 days (range, 122).
Cord pH (mean SD)
As shown in Table 2, infants from both sequence groups
Arterial
7.2 0.1
7.3 0.1
had higher posttransfusion hemoglobin (13.2 vs 11.8 g/dL,
Venous
7.3 0.2
7.3 0.1
P < 0.01) and hematocrit levels (38.6 vs 34.4 g/dL, P < 0.01)
SNAP score (mean SD)
22.5 7.3
21.6 7.1
following 20 mL/kg PRBC transfusions when compared to
SNAP indicates Score for Neonatal Acute Physiology.
15 mL/kg transfusions. There were no signicant dierences
in the incidence of hepatomegaly, edema, respiratory distress,
or abnormal vital signs during the 20 mL/kg transfusions comhigher hemoglobin and hematocrit values when compared to
pared to the 15 mL/kg transfusions. One patient (5%) had hep15 mL/kg transfusions. Infants tolerated the higher volumes
atomegaly following a transfusion of 15 mL/kg. Four patients
well, with no signicant dierences in the incidence of re(18%) had edema following transfusion, one after 15 mL/kg
spiratory distress, hepatomegaly, peripheral edema, hypoxia,
and three after 20 mL/kg transfusions. Necrotizing enterocolitis developed in one patient (5%), who
received 20 mL/kg followed by 15 mL/kg
2 days after the two transfusions were
Table 2. Pre- and posttransfusion treatment effects by dose
completed, requiring surgical interven15 mL/kg
20 mL/kg
tion. The infant survived to discharge.
Variable
DISCUSSION
Our findings support the efficacy
and safety of higher-volume (20 mL/kg)
PRBC transfusions, currently supported
by four similar studies. The larger transfusion volumes resulted in signicantly
April 2016
Hemoglobin (g/dL)
Hematocrit (g/dL)
Pre
Post
9.0 1.2 11.8 1.4
Pre
Post
P value
9.1 1.0 13.2 1.2
<.01
26.2 3.4 34.4 3.8 26.8 2.8 38.6 3.6
<.01
Red blood cells (M/L)
2.8 0.4
3.8 0.4
2.8 0.3
4.2 0.4
<.01
Respiratory distress (Silverman score)
2.1 1.1
2.2 1.0
2.2 1.3
2.2 1.2
.31
Safety and efficacy of packed red blood cell transfusions at different doses in very low birth weight infants
129
necrotizing enterocolitis, or vital sign insatiability. These ndings are consistent with a previous study by Wong et al in 2005
comparing 20 mL/kg with 15 mL/kg PRBC transfusions.
The randomized crossover design and the addition of the
SNAP-II score were strengths of this study. By randomizing the
sequence and having each infant serve as his or her own control, the observed changes in hemoglobin and hematocrit were
not biased by order of transfusion or by infant idiosyncrasies.
However, our study had several limitations. First, our study had
a limited sample size, which may have impacted our ability to
detect safety signal. However, our ndings add to the paucity of
data in this area. Second, our results may not be generalizable
to other centers with dierent transfusion practices. Finally,
the Silverman score is subject to ascertainment bias. Therefore,
further study in this area may address some of these limitations
and expand its scope.
Our ndings suggest that higher-volume PRBC transfusions lead to higher posttransfusion hemoglobin and hematocrit
volumes without increasing acute complications. These results
suggest a way to potentially decrease or eliminate the need for
multiple transfusions and the number of donors the infant is
exposed to, thereby decreasing risk. Prospective validation of this
practice, with larger studies, is needed to determine long-term
benets, safety prole, and cost-eectiveness.
1.
2.
130
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The safety and ecacy of red cell transfusions in neonates: a systematic
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Wong H, Connelly R, Day A, Flavin MP. A comparison of high and
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Luban NL. Review of neonatal red cell transfusion practices. Blood Rev
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Strauss RG. Transfusion therapy in neonates. Am J Dis Child
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Bell EF, Strauss RG, Widness JA, Mahoney LT, Mock DM, Seward VJ,
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Kirpalani H, Whyte RK, Andersen C, Asztalos EV, Heddle N, Blajchman
MA, Peliowski A, Rios A, LaCorte M, Connelly R, Barrington K, Roberts
RS. The Premature Infants in Need of Transfusion (PINT) study: a
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Simon TL, Alverson DC, AuBuchon J, Cooper ES, DeChristopher PJ,
Glenn GC, Gould SA, Harrison CR, Milam JD, Moise KJ Jr, Rodwig FR Jr, Sherman LA, Shulman IA, Stehling L. Practice parameter
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mist on obstructive respiratory signs, death rate and necropsy ndings
among premature infants. Pediatrics 1956;17(1):110.
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Volume 29, Number 2
Review of behavioral health integration in primary care at

Baylor Scott and White Healthcare, Central Region
John B. Jolly, PsyD, Norman R. Fluet, PsyD, Michael D. Reis, MD, Charles H. Stern, MD, Alexander W. Thompson, MD,
and Gillian A. Jolly, BS
The integration of behavioral health services in primary care has been

referred to in many ways, but ultimately refers to common structures and
processes. Behavioral health is integrated into primary care because it
increases the effectiveness and efficiency of providing care and reduces
costs in the care of primary care patients. Reimbursement is one factor,
if not the main factor, that determines the level of integration that can
be achieved. The federal health reform agenda supports changes that
will eventually permit behavioral health to be fully integrated and will
allow the health of the population to be the primary target of intervention. In an effort to develop more integrated services at Baylor Scott and
White Healthcare, models of integration are reviewed and the advantages
and disadvantages of each model are discussed. Recommendations to
increase integration include adopting a disease management model
with care management, planned guideline-based stepped care, followup, and treatment monitoring. Population-based interventions can be
completed at the pace of the development of alternative reimbursement
methods. The program should be based upon patient-centered medical home standards, and research is needed throughout the program
development process.
he Agency for Healthcare Research and Quality dened

integrated care as follows:
A practice team of primary care and behavioral health clinicians working together with patients and families, using
a systematic and cost-eective approach to provide patientcentered care for a dened population. This care may address
mental health and substance abuse conditions, health behaviors
(including their contribution to chronic medical illnesses),
life stressors and crises, stress-related physical symptoms, and
ineective patterns of health care utilization (1).
C. J. Peek, a national leader in care system development,

reported that a variety of terms are encountered within research
and conceptual writings of this emerging area, such as integrated
care, patient-centered care, coordinated care, shared care, collaborative care, colocated care, and integrated primary care or
primary care behavioral health (1). Kwan and Nease reported
that certain structural features and clinical processes are typical
of integrated behavioral health models (2). The common structural features are a care delivery team, a physical space onsite for
behavioral health, information technology, clinical and oce

management policies and protocols, and education and training. Common processes include access, detection, treatment,
practice improvement, and cost containment and sustainability.
They stated, Ultimately, it may not matter what exactly this
infrastructure looks like as long as it enables the provision of
certain services (2).
THE PURPOSE OF INTEGRATING BEHAVIORAL HEALTH WITH
PRIMARY CARE
There are a variety of forces demanding a change and redesign in how health care is delivered in the United States. These
forces include problems in the delivery of health care to patients
and their families, nancial pressures (including spiraling health
costs), and political forcesall pushing to support such changes
by delivery and payment reform.
Primary care continues to be the primary setting in which
individuals seek mental health treatment, yet treatment is often
decient. Wang and his colleagues reported that based upon
ndings from the National Comorbidity Survey Replication
data, 41.1% of individuals with mental disorders had received
treatment in the previous 12 months; 56% of those individuals
received treatment within the primary care setting, compared
with 44% who received treatment within mental health settings (3, 4). Consistent with a previous epidemiological study,
primary care is the de facto setting for mental health services
in the United States (5). However, Wang et al also found that
only 12.7% of individuals who were treated in primary care
received even minimally adequate treatment (3).
In addition to the need to become more clinically eective,
health care demands nancial redesign to bend the curve of
costs but also to support more eective, ecient, coordinated
care. Health care costs are spiraling, and the sick and disabled
consume almost all health dollars (6). Changes are particularly
From private practice, Jackson, Mississippi (J. B. Jolly); the Departments of

Family Medicine (Fluet, Reis, Stern) and Psychiatry (Thompson), Baylor Scott
and White Healthcare, Waco and Temple, Texas; and Baylor University, Waco,
Texas (G. A. Jolly).
Corresponding author: John B. Jolly, PsyD, 620 N. State Street, Suite 202,
Jackson, MS 39202 (e-mail: jollyjohndr@outlook.com).
131
needed to reduce costs of the chronically medically ill patient

with comorbid behavioral health concerns. Gaipa and colleagues
described a recent insurance report that demonstrated a signicant increase of cost when the particular medical condition
had comorbid behavioral health problems (7, 8). The authors
of the Air Forces Behavioral Health Optimization Program
stated that focusing only on the chronically sick does nothing
for the large pipeline that keeps fueling this re, and it has little
eect on the populations health as a whole (6). They proposed
a combination of addressing not only the sick and comorbid
but also the larger, healthier population.
Health care reform is supporting changes in not only clinical
delivery systems, but also payment and reimbursement systems.
Health care is moving from fee-for-service models to bundled/
global payments for populations of patients. The Patient Protection and Aordable Care Act (PPACA) and the Health Care and
Education Reconciliation Act of 2010 demonstrate this intent
with the federal health reform agenda. Fabius and colleagues
reported that the most signicant problem in health care reform
is the fee-for-service payment model (9). They noted that feefor-service deincentivizes the changes needed in delivery and
argued for bundling related costs. Under a fee-for-service model,
each provider bills separately and has no incentive to manage
their use eciently (9). By bundling or receiving global payments, providers are compensated based upon the combined
performance of all involved. The PPACA supports the testing of
this payment reform model to determine if providers can be incentivized to manage costs by taking responsibility for the costs
of both acute conditions/procedures and chronic conditions
(9). Medicare, Medicaid, and commercial insurance programs
are in the process of creating and releasing innovative bundled
and global payment plans to support models that are clinically
and cost-eective (10).
CONCEPTUAL DIMENSIONS USEFUL FOR INTEGRATION
In an eort to guide our process of behavioral integration
at Baylor Scott & White Central Region, we considered important conceptual dimensions in this emerging eld. Examining
eorts in terms of an integration continuum, patient populations (whether in terms of level of pathology or even insurance
status), or conceptual models of collaborative activities provided
a direction (1114).
Doherty described ve levels of integration: minimal collaboration, collaboration at a distance, basic collaboration on
site, close collaboration in a partly integrated system, and a
fully integrated system (11). The rst two integration levels
suer from a lack of communication, particularly involving
comorbid mental health and physical health problems, while
a fully integrated system requires a change in reimbursement
methods that is currently unavailable. Basic collaboration on
site occurs when behavioral health providers (BHP) and primary
care providers (PCP) have separate systems but share the same
facility. Proximity allows for more communication, but each
provider remains in his or her own professional culture. In the
fourth level of integration, some organizations have close collaboration in a partly integrated system; BHPs and PCPs share
132
the same facility and have some systems in common, such as

scheduling appointments or medical records. They have regular
face-to-face communication. There is a sense of being part of
the larger team. The fth level of integration is a close collaboration in a fully integrated system. The BHP and PCP are part
of the same team. The patient experiences the mental health
treatment as part of his or her regular primary care. There is a
population-based focus with primary prevention in addition to
integrative case management.
Another conceptual dimension that aects integration efforts considers the importance of patient populations. Mauer
proposed the four-quadrant model (12), which divides patients
into four categories based upon behavioral and physical needs
and risks. Patients with low behavioral health needs/risks and
low physical health needs/risks are typically served in primary care.
Patients who have high behavioral health needs and low physical
health needs are typically served in specialty behavioral health
programs with linkages to primary care. Patients who have low
behavioral health needs and high physical health needs are served
in primary care and in the medical specialty system. Finally,
patients who have high behavioral health needs and high physical health needs are typically served in both specialty behavioral
health settings and primary care.
Another patient population model places integration in
the context of behavioral health reform to determine what
type of model of care best nancially incentivizes integration
for particular patient populations. Bao et al discussed grouping patients based upon severity of mental health problems
and insurance status (13). If a patients behavioral/mental
health is paid by Medicaid, access is poorer, there is typically
a greater need for social and human services, and coordination and collaboration between primary and behavioral health
care is traditionally lacking. The Aordable Care Acts health
home provisions incentivize coordinated care for Medicaid
patients who have chronic and comorbid clinical conditions.
For patients, regardless of health status, whose health is paid
for by commercial insurance and Medicare programs, patientcentered medical homes (PCMHs) and accountable care organizations best incentivize integration eorts (15). The Agency
for Healthcare Research and Quality reported that a PCMH
has ve functions and attributes: providing care that is a) comprehensive, b) patient-centered, c) coordinated, d) accessible,
and e) has a commitment to quality improvement (16). Bao
et al reported that PCMHs have the greatest potential to serve
patients with mild to moderate behavioral health conditions
(13). The Patient-Centered Primary Care Collaborative Payment Reform Task Force has oered a range of payment plans
with delity to the PCMH model; at the highest level, global
payments with bonuses are proposed to lessen the need for
patient volume and incentivize value creation (17, 18). Accountable care organizations have shared savings for coordinating medical and behavioral health care but are payer-specic;
they lack incentives to improve quality and reduce costs for
Medicaid patients (13).
A particularly useful framework to guide integration eorts
was provided by Collins and his colleagues (14). They discussed
Volume 29, Number 2
eight models of behavioral health integration that described

nonintegrated to fully integrated services. The colocation,
disease management, and primary care behavioral health
models appear to be particularly relevant in discussions of the
current status and future transitions of behavioral integration
at Baylor Scott and White Healthcare. The colocation model
occurs when PCPs and BHPs are at the same site, but have
distinct services. This arrangement has the primary advantage of
providing better communication. Foy and colleagues suggested
that better interactive communication, dened as collaborative
arrangements that enable primary care physicians and specialists
to converse, improves outcomes (19). The colocation model is
less stigmatizing and provides better access to behavioral healthcare for PCPs and their patients. One disadvantage is that patients referred to mental health for physical complaints may
interpret symptoms as being all in my head. Additionally, if
the behavioral service location is separate from the primary care
treatment setting, e.g., a dierent wing of the building, there
may be fewer opportunities for interactions and education of
PCPs and warm hand-os. These diculties are intensied if
BHP therapeutic hours are not modied for the primary care
15- to 20-minute appointments. Caseloads can quickly become
overloaded, and access problems increase.
The disease management model is an integrated system
of interventions to optimize functioning of patients and to
impact the overall cost of the disease burden (14). The chronic
care or disease management model is based on Wagner, Austin,
and Von Kors chronic care model (CCM) (20). Wagner
et al suggested that the components of high-quality chronic
care consist of the use of explicit plans and protocols, practice
redesign, patient change processes, expert input, and information system support (20). Common elements of chronic care
include collaboration between service providers and patients,
care plans, self-management education, follow-up, treatment
monitoring, targeted use of specialty referral, and stepped
care (21, 22).
The disease management model has advantages over the
colocation model. In addition to having all the strengths of
being on site, patients are screened for psychological problems
in an empirical manner and closely monitored throughout the
treatment process; this allows for modication and personalization of the intervention process and results in stepped care.
Empirical guidelines are emphasized, saving scarce psychiatric
resources to be used more eciently. One primary disadvantage
of this model is the current fee-for-service payment method,
which does not reimburse case management services.
The primary care behavioral model is based upon population-based care. Strosahl reported that population-based care
is grounded in public health concepts (23). Further, primary
care behavioral health is consistent with the philosophy, goals
and strategies of primary care medicine. Specically, there is
an emphasis on early identication and treatment, long-term
prevention, and wellness (24). Collins et al indicated that
the entire primary care patient population is the target of assessment, intervention, and consultative services (14). The primary customer is the PCP, then the patient. The goals are to
April 2016
support providers, improve their eectiveness, prevent chronic

problems from occurring, and improve the overall health of
the population. The most critical issue in utilizing this model
is associated again with reimbursement. While there appear
to be new eorts at paying for such population-based services
as consultation, case management, and primary prevention,
currently medical oset savings for this model have not been
clearly demonstrated.
CLINICAL EFFECTIVENESS OF BEHAVIORAL HEALTH
INTEGRATION
Metaanalyses of behavioral health integration studies have
demonstrated the clinical eectiveness of collaborative care
models with a variety of clinical conditions. In the most comprehensive metaanalysis completed to date, Woltmann and
colleagues examined the clinical eectiveness of collaborative
CCMs for mental health conditions across dierent settings,
particularly for depression but also including bipolar disorder,
anxiety, and other mental health problems (25). They compared CCMs to usual care for 57 experimental trials across 78
articles, with 140 clinical outcome analyses. To be included in
the study, each CCM had to have six components consistent
with the CCM: patient self-management support, delivery
system redesign, use of clinical information systems, provider
decision support (guidelines), health care organization support, and linkage to community resources (25). Of 133 study
analyses that reported statistical comparisons, 66 analyses
(49.6%) favored the CCMs, 1 favored the control condition,
and 66 (49.6%) had no statistically signicant dierences in
the comparisons. The overall ndings suggested that there were
small to medium eects of CCMs across multiple disorders
for clinical outcome (symptoms), mental and physical quality of life, and social role functioning. The authors reported
that at this point, we still do not know which components are
most important, which are necessary, and what works better
for whom.
Most metaanalyses have cited the contribution of care
management in the treatment of mental health problems, particularly for depression. Butler and her colleagues conducted
a metaanalysis of 33 clinical trials from 145 articles on the
integration of behavioral health and primary care in the treatment of depression (26). They specically examined integration based upon the use of care managers, the process of care,
and the degree that the studies integrated the roles of clinicians. The authors concluded that most studies demonstrated
positive outcomes for treatment response and remission rates.
However, the level of integration was unrelated to outcomes.
Gilbody and colleagues completed a cumulative metaanalysis
of 37 randomized collaborative care studies treating depression
(27); all studies utilized case managers. They found a signicant positive treatment eect, when compared to standard of
care, at 6 months. Eleven studies examined eects beyond 6
months; signicant treatment eects were found at 12 months,
18 months, and 5 years. Case management supervision and
mental health background were found to be signicantly related to the size of positive treatment outcome. Gilbody et al
Review of behavioral health integration in primary care at Baylor Scott and White Healthcare, Central Region
133
also reported that studies that had a case manager, a PCP, and
access to specialist input, consistent with Katon and colleagues
collaborative care model (22), tended to be more eective than
other models (27).
Williams et al completed a systematic review of 28 studies
that used care management and interventions treating depression within primary care settings (28). Consistent with Wagner
and colleagues CCM, most studies included patient education
and self-management, monitoring of symptoms, decision support, registries, and mental health supervision of care managers
(20). The authors found that almost all multifaceted interventions led to signicant improvements in depression outcomes
within 1 year. Gensichen et al found case management to be the
primary positive factor in depression outcomes in a metaanalysis
of 13 studies within primary care settings (29).
Instead of a specic focus on care management, Foy and
colleagues suggested that the important factor in patient success is interactive communication of PCPs and specialists
(19). In a metaanalysis of 18 depression studies that excluded
care managers but incorporated direct communication between
PCPs and psychiatrists, the authors found signicant reductions
in patients depression. They concluded that collaboration that
allows for direct communication between the PCP and specialist
improves patient outcomes.
In sum, collaborative care, based upon a CCM, demonstrates clear evidence for eectiveness. The most eective studies
consist of care management, a PCP, and some form of specialist
consultation and supervision.
BAYLOR SCOTT AND WHITE CLINICS

Clinic patient characteristics
Baylor Scott and White Healthcare-Central Region, Department of Family Medicine, has two primary care clinics that
have BHPs. The Waco Clinic (WC) is located in Waco, Texas, a
city of 127,000 within a county of 238,000. The Killeen Clinic
(KC) is located within a city of 134,000 in a county of 323,000.
Fort Hood, one of the largest military installations in the world,
is located in Killeen. WC, which has had a psychology presence for the past 20 years, has four providers: three licensed
psychologists and one licensed professional counselor. WC has
always functioned with an annual prot margin while maintaining traditional 50-minute therapeutic hours. Contrary to Strosahls concern about therapists being swamped, WC functions
without a long waiting list. In comparison to a non-colocated
clinic, WC demonstrated a statistically signicant shorter time
from PCP referral to rst BHP appointment for older patients,
with approximately 77% of all patients attending their initial
appointment after being referred by the PCP (31). KC hired two
licensed psychologists within the past year. The Table shows the
Table. The mental health patient populations of two primary care

clinics with behavioral health providers in Baylor Scott & White
Central Region, calendar year 2013
Killeen Clinic Waco Clinic
Clinic population
28,000
17,000
Female
74%
63%
Caucasian
59%
85%
African American
17%
7%
44
42
Anxiety
83%
76%
Depression
68%
59%
Substance abuse
12%
8%
Conduct disorders
7%
16%
Obesity
23%
47%
Demographics
COST-EFFECTIVENESS OF BEHAVIORAL HEALTH INTEGRATION

Behavioral health integration is clinically eective. Is it
also cost-eective? Woltmann et al argued, The major focus
of health care cost reduction eorts must be in reducing avoidable complications of chronic illnesses, which account for up to
22% of all health care expenditures. Reducing these complications could realistically result in a $40-billion per-year savings
(25). Strosahl stated, While improving clinical outcomes in
healthcare is obviously an important goal, the straw that stirs
the drink is the huge medical oset potential of integrated care
(23). He suggested that integrated care has the potential for cost
oset of approximately 20% to 40%.
Woltmann and colleagues examined health care costs in
their metaanalysis of collaborative CCMs for mental health
conditions (25). They found that among the 21 economic
analyses (among 57 clinical eectiveness trials examined),
only 10 could be compared; 9 (90%) found no statistically
signi cant di erence in costs between the CCM and the
control condition. One study found the control condition
less expensive. Van Steenbergen-Weijenburg and colleagues
found eight studies that met quality criteria examining the
cost-eectiveness of collaborative care for major depression
(30). They found that all studies demonstrated that collaborative care is eective but, in most cases, more expensive.
They concluded that while collaborative care seems promising, the economic information is insucient for policy
decisions (30).
134
Median age (years)

Psychiatric diagnoses (overlapping)
Comorbid chronic health conditions

Diabetes
17%
7%
Asthma
14%
9%
Other problems
<5%
<5%
91%
61%
Referrals
From clinic PCPs
From other BSW-CR clinics
20%
Reimbursement
Commercial insurance
48%
30%
Scott & White Plan
16%
31%
Medicare
18%
14%
Medicaid
10%
10%
PCP indicates primary care physician; BSW-CR, Baylor Scott & White Central Region.
Volume 29, Number 2
similarities and dierences in the clinics mental health patient

populations.
Clinic structural and process features
Both clinics have a close collaboration within a partly integrated system (11). Both clinics appear to be composed largely
of patients with low behavioral health needs/risks and low physical health needs (12). While the clinics use a fee-for-service
model of reimbursement, 90% of the payers for both clinics are
non-Medicaid; PCMHs and accountable care organizations best
incentivize integration eorts (13). At this time, both clinics
t the colocation model with integration enhancements (14).
The Patient-Centered Integrated Behavioral Health Care
Principles and Tasks, a qualitative assessment of our adherence
to principles and tasks considered important for behavioral
health integration, was completed (32). The major strengths
of both clinics are that PCPs and BHPs are colocated, they
oer evidence-based treatments for their patients and families,
and they systematically identify problems for most patients.
Advantages of colocated services include easy, nonstigmatizing
access for primary care patients, curbside consultations and
improved communication with PCPs, and shared electronic
medical records. Consultations to PCPs are limited, however, by
the 50-minute hour; BHPs are not easily accessible except when
suicidal/homicidal ideation is prominent. While KC providers
share treatment space, WC providers are in separate wings of
the clinic. There are many advantages to shared space, but also
disadvantages; administrative issues appear less complicated
with services in separate wings. Both clinics have a goal of educating PCPs concerning psychological/behavioral issues, given
that behavioral health plays such an important role in primary
care (3). In both clinics, the PCPs and BHPs collaborate using
care plans within the shared electronic medical records. While
both clinics use measurement-based identication of behavioral
and emotional problems, and develop and modify treatment
plans based upon this data, these eorts are not completed
systematically at this point. Both clinics use valid measurement
tools to screen, diagnose, and even document baseline symptom severity. WC and KC provide initial evaluations that rely
primarily on interview and self-report measures, such as the
Patient Health Questionnaire-9 and the Generalized Anxiety
Disorder 7-item scale (33, 34). WC BHPs oer general psychopharmacology consultation, within their scope of practice,
comfort level, and training, and based upon ethical guidelines.
Among KC and WC behavioral health care patients, 48% and
31%, respectively, are treated with psychotropic medications.
For those patients who have severe mental illness and/or need
more complicated psychopharmacological intervention, referrals
are made to psychiatrists at Baylor Scott and White in Temple,
Texas. This service is located 30 or more miles from WC and
KC and has a 2- to 3-month waiting list for nonemergency
patients. Less than 5% of behavioral health patients for both
clinics were referred to psychiatrists.
While there is active communication among PCPs and
BHPs in both clinics, particularly with the shared electronic
medical record, there is no formal care coordination or case
April 2016
management. The lack of case management clearly sets limits on

being responsive to patients changing needs. The clinics newest
electronic medical record has a registry, which will allow both
clinics to track and monitor patients who are not improving;
neither clinic has begun this process yet. Providers are formally
assessed for patient satisfaction, and, while accountable, providers are not reimbursed for quality of care and patient outcomes.
Integration recommendations for Baylor Scott and
White-Central Region
Based upon a review of current concepts and models of
behavioral health integration with primary care, the ecacy of
certain structures and processes, and the cost-eectiveness of
programs in use, the following recommendations are oered.
First, research studies on the ecacy and cost-eciency of
collaborative care clearly support the need and role for a care
manager who is responsible for patient education and involving
the patient in the treatment process. After initial assessment,
patients may be triaged to simple monitoring with education;
discussion of guideline-based PCP-provided medication or
therapy options; possible initiation of short-term, problemsolving, or cognitive-behavioral treatment; or close continual
monitoring. The registry will permit close monitoring and a
treatment-responsive approach to care. Patients who are not
progressing may be moved to the next level of stepped care.
The primary goal is patient progress for lower cost.
Second, the program should adhere to PCMH standards,
which require certain types of tasks to be completed with the
majority of patients to ensure that care is patient-centered, coordinated, eective, and ecient (15).
Finally, research is needed to assess and monitor the ecacy and cost-eciency of Baylor Scott and Whites behavioral
health integration program. Assessment needs to be completed
with empirically based measures that are sensitive to change.
Important questions include, for example, whether the program
demonstrates greater eectiveness and eciency than previous
care. In sum, there is a need for research to assess and guide program changes in order to be more clinically and cost-eective.
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Volume 29, Number 2
Invited Commentary
f you turn over your commercial health insurance card, it

is likely to state in small print that for behavioral health
coverage call 1-800-xxx. In the US, behavioral health has
for at least the last 20 years been largely carved out to behavioral managed care provider organizations. As a practicing
family physician, I was often frustrated to direct my patient
needing counseling or additional behavioral intervention to
such obscure and nonintegrated resources. When the patient
did access the resource, there was no exchange of data between
me and the behavioralistno reports, no dialogue, no discussion of comorbid conditions. Unless the patient came back to
me and self-reported the behavioral therapy or psychotropic
medications, there was a complete separation between his/her
health care and behavioral care. But carved-out managed behavioral care is changing (1), and as Jolly et al indicate in their
well-researched article (2), there is growing recognition of the
value of integrating behavioral care with general health care.
Virtually all physicians realize that psychological and behavioral factors are involved in clinical outcomes of both acute
and chronic diseases (diabetes, asthma, heart failure), lifestylemodiable conditions (obesity, smoking cessation), as well as
primary behavioral illnesses (depression, anxiety). Extensive
literature has clearly shown that inadequately addressed behavioral conditions add great cost to population health and
fail to produce needed outcomes. Staggering sums of direct
and indirect costs of mental illness have been described (3).
Insel considered the entire eld of mental health to be ripe for
clinically eective and cost-eective intervention (3).
As we described in our recently published Baylor Scott &
White book, true accountable clinical integration can knit complex polymorbid patient care into improved outcomes, and
simultaneously decrease costs (4). One key success factor will
surely be reintegrating behavioral care into the general health
care setting. The authors propose several levels of integration,
which for most patients other than those with severe mental
illness are ideally delivered in coordination with primary care.

The greatest barrier seems to be payment. Fee-for-service payment poorly supports the integrated care coordination and
multilevel behavioral therapy structure that can produce best
outcomes when integrated with the individuals medical home.
Primary care physicians are trained to be comprehensivists (5),
yet that model of payment produces transactionalists who are
better remunerated to treat episodes and to avoid probing into
the behavioral components that underlie outcomes of illness
and population health.
Models such as the colocation and more ideally the disease
management approach utilizing the structure of the patientcentered medical home are needed. Collecting outcome data for
both quality and cost-eectiveness will be extremely important.
Baylor Scott & Whites leadership in population health will support exploration and determination of more ideal approaches
to behavioral care.
Carl Couch, MD
Baylor Scott & White Health, Dallas, Texas
E-mail: Carl.Couch@BSWHealth.org
1.
2.
3.
4.
5.
Dalzell M. Mental health: under ACA is it better to carve in or to carve

out? Managed Care, December 2012. Available at http://www.managedcaremag.com/archives/1212/1212.mental_health_carve.html; accessed
January 25, 2016.
Jolly JB, Fluet NR, Reis MD, Stern CH, Thompson AW, Jolly GA.
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and White Healthcare, Central Region. Proc (Bayl Univ Med Cent)
2016;29(2):131136.
Insel T. The global cost of mental illness [Directors blog entry, National
Institute of Mental Health, September 28, 2011]. Available at http://www.
nimh.nih.gov/about/director/2011/the-global-cost-of-mental-illness.shtml;
accessed January 25, 2016.
Couch C. Accountable: The Baylor Scott & White Quality Alliance Accountable Care Journey. Boca Raton, FL: CRC Press, 2016:1921.
Couch, Accountable: 116118.
137
Medical and surgical care during the American Civil War,

18611865
Robert F. Reilly, MD
This review describes medical and surgical care during the American Civil
War. This era is often referred to in a negative way as the Middle Ages of
medicine in the United States. Many misconceptions exist regarding the
quality of care during the war. It is commonly believed that surgery was
often done without anesthesia, that many unnecessary amputations were
done, and that care was not state of the art for the times. None of these
assertions is true. Physicians were practicing in an era before the germ
theory of disease was established, before sterile technique and antisepsis
were known, with very few effective medications, and often operating
48 to 72 hours with no sleep. Each side was woefully unprepared, in all
aspects, for the extent of the war and misjudged the degree to which
each would fight for their cause. Despite this, many medical advances
and discoveries occurred as a result of the work of dedicated physicians
on both sides of the conflict.
Table 1. Medical and surgical advances during the war

Type
Medical
Advances
Use of quinine for the prevention of malaria
Use of quarantine, which virtually eliminated yellow fever
Successful treatment of hospital gangrene with bromine and
isolation
Development of an ambulance system for evacuation of the
wounded
Use of trains and boats to transport patients
Establishment of large general hospitals
Creation of specialty hospitals
Surgical
Safe use of anesthetics

Performance of rudimentary neurosurgery
Development of techniques for arterial ligation
he Civil War was fought in over 10,000 places and was

the bloodiest war in the history of the United States. Two
percent of the population at the time (approximately
620,000) died during the conict (1). More Americans
died in the Civil War than in all other wars combined. As hard as
it is to believe, these numbers may actually be an underestimate
of the death toll, given that much of the data regarding deaths
of Confederate soldiers was destroyed when Richmond burned
on April 2, 1865. More recent estimates based on comparative
census data put the gure closer to 752,000 (2). Countless other
soldiers were left disabled. The year after the war ended, the
state of Mississippi spent 20% of its annual budget on articial
limbs for its veterans (3).
Many misconceptions exist regarding medicine during the
Civil War era, and this period is commonly referred to as the
Middle Ages of American medicine. Medical care was heavily
criticized in the press throughout the war. It was stated that
surgery was often done without anesthesia, many unnecessary
amputations were done, and that care was not state of the
art for the times. None of these assertions is true. Actually,
during the Civil War, there were many medical advances and
discoveries (Table 1).
Twice as many soldiers died of disease during the war than
in combat (3). This was a marked improvement compared with
the Mexican War (18461848), where there were 7 to 10 deaths
138
Performance of the first plastic surgery
from disease for every death in battle. It was not until World War
II that weapons killed more Americans than disease. The war left
about 1 in 10 able-bodied Union soldiers dead or incapacitated,
versus 1 in 4 in the Confederate Army (3).
WHY DID SO MANY DIE?
Soldiers died from two general causes: battleeld injuries
and disease. Contributing factors to combat-related deaths were
inexperienced surgeons; the lack of a coordinated system to
get the injured o the battleeld quickly; wound infections,
since sterile technique was not yet recognized as important;
and battleeld tactics that did not keep pace with advances in
weaponry. Contributing factors to disease-related deaths included poor sanitation and overcrowded camps; the ignoring of
sanitation by line ocers; inadequate pre-enlistment screening
From the Division of Nephrology, Medical Service, Veterans Affairs North Texas
Health Care System, Dallas, Texas, and the Division of Nephrology, Department
of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Corresponding author: Robert F. Reilly, MD, Veterans Affairs North Texas Health
Care System, Nephrology Section, MC 111G1, 4500 South Lancaster Road,
Dallas, TX 75216-7167 (e-mail: Robert.reilly2@va.gov).
of recruits; poor diet; lack of immunity to childhood diseases;

and few specic treatments for disease.
Army Regulation 1297 set out criteria for preinduction
physical exams:
In passing a recruit the medical ocer is to examine him
stripped; to see that he has free use of all his limbs; that his
chest is ample; that his hearing, vision and speech are perfect;
that he has no tumors, or ulcerated or extensively cicatrized
legs; no rupture or chronic cutaneous aection; that he has
not received any contusion, or wound of the head, that may
impair his faculties; that he is not a drunkard; is not subject
to convulsions; and has no infectious disorder; nor any other
that may unt him for military service (4).
That was the requirement; however, the reality was that many
exams early in the war were of poor quality. Governors needed
to ll quotas, and examining physicians were paid per recruit.
If you could walk, carry a gun, and had front teeth and a trigger nger, you could enlist. Front teeth were needed in order to
tear open the cartridge containing gunpowder and the bullet.
Dental care was poor in the 1860s, and this was a frequent cause
of rejecting a recruit. It was the origin of the term 4F (missing
4 front teeth). The system was so poor that it is estimated that
about 250 women served as soldiers during the war (5). The
quality of physical exams improved with the Civil War Military
Draft Act of 1863, when nes and prison sentences were put in
place for physicians who were derelict in their duties, resulting
in many more recruits being rejected from service.
To better comprehend medical care delivered during this
period, it is important to understand the medical infrastructure
at the time. The rst medical school was established in the
United States in Philadelphia in 1765. There was no prerequisite
preparation for admission, no entrance exam, and no state medical licensing boards. Medical school was 2 years in duration. In
the rst year, lectures were given in two 4-month semesters. The
second year was a repetition of the rst. Students did not have
any clinical experience prior to graduation. Medical schools at
the time were more like proprietary schools. There was a large
entrance fee and as a result very few students ever failed (6). The
Flexner Report was still 50 years in the future, which required
2 or more years of college and a 4-year curriculum. In 1862,
there were only six colleges of pharmacy in the US. Most doctors
prescribed, compounded, and dispensed their own medications.
The germ theory of disease would not be established until
1870 and Kochs postulates in 1890. Disease was thought to be
a result of either direct or indirect inammation (7). Indirect
inammation was thought to be caused by excess blood ow to a
tissue, a theory promulgated by a prominent 18th-century physician, Benjamin Rush. This led to the concept that bloodletting
might be benecial. By the time of the Civil War, bloodletting
had largely fallen out of fashion.
Before the war, the United States had a peace time army of
16,000 soldiers. There were 113 doctors in the army. At the start
of the war, 24 went south and 3 were dismissed for disloyalty
(8). At the end of the war, there were over 12,000 doctors in the
Union Army and over 3000 in the Confederate Army. Before
April 2016
the war, the largest military hospital was at Fort Leavenworth,

which had 40 beds. The only hospital in Washington, DC, before the war was a two-story six-room building used to isolate
smallpox patients.
The rst major battle of the war fought at Bull Run in
Manassas, Virginia, on July 21, 1861, illustrates how woefully
unprepared the Union was from a medical standpoint at the
start of the war. Fortunately, at Bull Run, casualty gures were
not large compared with future battles (North, 481 killed, 1011
wounded; South, 387 killed, 1582 wounded) (9). Despite this,
many problems were encountered. There was no military ambulance corps. Ambulances were driven by civilians who ed when
the rst shots were red. If they left the ambulances behind,
healthy soldiers stole them to ee back to Washington, DC. Not
a single wounded soldier returned to Washington, DC, in an
ambulance (10). Tragically, wounded soldiers remained on the
battleeld for days, the rst two spent in the rain. Incredibly,
Surgeon General Finley did not order medical supplies until
after the battle was over.
ORGANIZATION OF BATTLEFIELD MEDICAL CARE
How medical care was delivered on and o the battleeld
changed during the war. Early on, stretcher bearers were members
of the regimental band, and many ed when the battle started.
Soldiers acting as stretcher bearers rarely returned to the front
lines. As the war evolved, stretcher bearers became part of the
medical corps. At the battle of Antietam, there were 71 Union
eld hospitals. As the war went on, these were consolidated. There
were ambulances here that were used to bring the wounded to
temporary battleeld hospitals, which were larger, often under
tents, and out of artillery range. Later in the war, patients were
transported to large general hospitals by train or ship in urban
centers. These did not exist when the war began. There was no
military ambulance corps in the Union Army until August of
1862. Until that time, civilians drove the ambulances. Initially
the ambulance corps was under the Quartermaster corps, which
meant that ambulances were often commandeered to deliver
supplies and ammunition to the front. Jonathan Letterman set
up his own ambulance corps in the East under General George
McClellan. Medical directors chose all the soldiers for their services. Ambulances could not be used for other purposes, and only
the ambulance corps was allowed to remove wounded from the
battleeld. Letterman was responsible for a number of organizational improvements within the Army of the Potomac and was
given a free hand by McClellan to implement them.
Large general hospitals were established by September of
1862 (11). These were in large cities, and soldiers were transported there by train or ship. At the end of the war, there were
about 400 hospitals with about 400,000 beds. There were 2
million admissions to these hospitals with an overall mortality
of 8%. In the South, the largest general hospital, Chimborazo,
was in Richmond, Virginia. It was built out of tobacco crates
on 40 acres. It contained ve separate hospitals, each made up
of 30 buildings. There were 150 wards with 40 to 60 patients
per ward. The census was as high as 4000. They treated about
76,000 patients with a 9% mortality (12).
Medical and surgical care during the American Civil War, 18611865
139
Table 2. Types of weapons and number of wounds treated*

Type of weapon
Number
% of recorded cases
Conoidal (Mini) ball
108,049
76.0%
Round or musket ball
16,742
12.0%
Fragment of shell
12,520
9.0%
Pistol or buckshot
3,008
2.0%
Grape, canister, etc.
1,153
1.0%
359
0.3%
139
0.1%
Solid shot
Explosive musket ball
Unknown missile
103,829
*From Bollet AJ, Civil War Medicine: Challenges and Triumphs, Table 3.1, p. 84. Copyright 2002 by Galen Press, Ltd. All rights reserved. Reprinted with permission of Galen
Press, Ltd., Tucson, AZ.
COMBAT-RELATED INJURIES
Before interpreting the data regarding combat-related injuries, it is important to recognize limitations in the reporting. In
order to be reported, a soldier had to be either transported to
or make it back to a eld hospital, and this may have resulted
in an underreporting of deaths from cannon re. As shown in
Table 2, most injuries resulted from the Mini ball invented by
the French ocer Claude-Etienne Mini in 1849. The Mini
ball is a 0.58-caliber bullet that is slow moving and is made from
soft lead. It attens on impact and creates a wound that grows
larger as the bullet moves deeper into tissues. It shatters bone
above and below impact and usually does not exit. Because of
its relatively slow muzzle velocity, it brought bits of clothing,
skin, and bacteria into the wound. The majority of gunshot
wounds occurred in the upper and lower extremities, but the
fatality rate from these wounds was low (Table 3). Only 18% of
wounds were to the abdomen, but these were more often fatal
from intestinal perforation in the preantibiotic era.
Commanders in the eld were also slow to adjust their tactics in keeping with advances in weaponry. In the Revolutionary
War era, smooth bore muskets were accurate only up to about
50 yards and were dicult to reload quickly, making rapid
repetitive ring dicult. However, newer ried muskets in use
after the rst year of the war were accurate up to 500 yards,
Table 3. Distribution of wounds among those listed as killed in
battle or admitted to hospitals*
Site
Killed in battle
Wounded
Trunk
51%
18%
Head and neck
42%
11%
Lower extremities
5%
35%
Upper extremities
3%
36%
Press, Ltd., Tucson, AZ. Compiled from data in Medical and Surgical History, Surgical
Section, vol. 3, p. 692.
140
and troops could easily re them at a rate of 3 times a minute

and sometimes faster. In the Revolutionary War, men could
charge a xed entrenched position with the possibility of success,
whereas in the Civil War this same tactic was sure to fail. This
was evidenced by the catastrophic failures of Pickets charge at
Gettysburg in the East, and Hoods charge at Franklin, Tennessee, in the West. Six high-ranking Confederate generals were
killed at the battle of Franklin, where over 1750 men died in a
5-hour period, with another 5500 wounded or captured (13).
Perhaps the most famous example of a lack of appreciation
for the improvement in weaponry by those in high command
occurred at the Battle of Spotsylvania Courthouse. John Sedgwick was the highest ranking Union general killed in the war.
While directing troop movements at Spotsylvania Courthouse,
he scolded his men for dodging bullets from sharpshooters concealed in the distant woods. I am ashamed of you dodging
that way. They couldnt hit an elephant at this distance (14).
Moments later a bullet red from more than 500 yards struck
him in the head, killing him instantly.
SURGICAL PROCEDURES
Three of every four surgical procedures performed during
the war were amputations. Each amputation took about 2 to 10
minutes to complete. There were 175,000 extremity wounds to
Union soldiers, and about 30,000 of these underwent amputation with a 26.3% mortality. The further from the torso the
amputation was carried out, the greater the survival (Table 4).
As the war went on, it was noticed that if amputation was
done within 24 hours, mortality was lower than if performed
Table 4. Deaths from amputation for the British Army in
the Crimean War and the Confederate Army of
Northern Virginia, 1863*
Amputation
site
British Army
in the Crimea:
Deaths (%)
Hip
100%
Confederate Army of Northern

Virginia: Deaths (%) based on timing
of amputation
Under 48 hours
After 48 hours
66%
Thigh
56%
38%
73%
Shoulder joint
33%
31%
71%
Lower leg
30%
30%
49%
Arm
26%
14%
37%
Foot
23%
3%
12%
5%
12%
22%
Forearm
Press, Ltd., Tucson, AZ. Crimean War data: Cantlie N, A History of the Army Medical
Department, Vol. 2. Edinburgh: Churchill Livingston, 1973. Confederate Army of Northern
Virginia data: Sorrel P, Gun-shot woundsArmy of Northern Virginia. Conf States Med
Surg J 1864;1(10):153 and Chisolm JJ, A Manual of Military Surgery for Use of the
Surgeons in the Confederate Army, 3rd ed., 1864; republished: Dayton, OH: Morningside
Press, 1992, p. 361.
Hip meant an amputation high on the femur, near the hip joint. Thigh usually meant
an amputation near the middle of the femur, although sometimes the location was
specifically described as upper third or lower third.
Volume 29, Number 2
after more than 48 hours. Only about 1 in 15 Union physicians was allowed to amputate. Only the most senior and
experienced surgeons performed amputations. These changes
were put into eect because of the public perception that too
many amputations were being performed. Amputations were
not carried out using sterile technique, given that Listers
classic paper on antisepsis did not appear until after the war
in 1867 (15).
Anesthesia was rst introduced in the United States in the
1840s. During the Civil War, it was used in over 80,000 cases.
Chloroform was preferred because it had a quicker onset of action, could be used in small volumes, and was nonammable.
During the war there were only 43 anesthesia-related deaths.
Anesthesia was fairly light (stage II) leading to the misperception
that it was not being used.
Postoperative wound infections, when they developed, were
a serious problem in the preantibiotic era. Laudable pus was
thick and creamy (thought to be due to Staphylococcal infection) and associated with a better prognosis than malignant pus,
which was thin and bloody (thought to be due to Streptococcal
infection). Hospital gangrene was a peculiar type of necrotizing fasciitis that was rst seen in the larger general hospitals. It
was probably a result of a Streptococcal infection since nurses
taking care of these patients occasionally developed erysipelas,
but the exact organism remains unknown. A large percentage of
patients with it died (45%) (8). Treatment was to dissect away
dead tissue and inject the wound margins with bromine under
anesthesia. The wound was then packed with a bromine-soaked
dressing and the patients isolated in separate tents with a separate bandage supply. Nurses dressed these patients wounds last
and washed their hands in chlorinated soda between patients.
NONCOMBAT-RELATED DEATH AND ILLNESS
A variety of factors contributed to a high rate of noncombatrelated illness, including overcrowded and lthy camps. Latrines
were often not used or were drained into drinking water supplies or not covered daily. Food quality was poor from several
standpoints. It was poorly stored, poorly cooked, and lacked
enough vitamin C to prevent scurvy. The Army of the Potomac
eventually added a number of rules: camps had be pitched on
new ground and drained by ditches 18 inches deep, tents had
to be struck twice a week to sun their oors, cooking had to
be done only by company cooks, all refuse had to be burned
or buried daily, soldiers had to bathe twice a week and change
clothing at least once a week, and latrines had to be 8 feet deep
and covered by 6 inches of dirt daily.
There were few useful medications at the time, and about
two thirds of all drugs were botanicals. In 1860 Oliver Wendell
Holmes stated at the annual meeting of the Massachusetts Medical Society, I rmly believe that if the whole materia medica, as
now used, could be sunk to the bottom of the sea, it would be all
the better for mankind,and all the worse for the shes (16).
Medications that were helpful included quinine for malaria,
morphine, chloroform, and ether, as well as paregoric. Many
others were harmful. Fowlers solution was used to treat fevers
and contained arsenic. Calomel (mercurous chloride) was used
April 2016
for diarrhea. Mercury is excreted in high concentration in saliva.

This led to excessive salivation, loss of teeth, and gangrene of the
mouth and cheeks in some patients. There were several famous
cases of calomel toxicity. One involved Louisa May Alcott, the
author of Little Women, and the second Carleton Burgan. He
was one of the rst people to undergo plastic surgery in the
United States. Dr. Gurdon Buck performed a series of ve operations using skin from his forehead to rebuild his cheek and
side of his nose.
Physicians at the time had an extraordinary workload. The
following was excerpted from a letter Dr. Daniel Holt wrote to
his wife, Euphrasia:
You cannot imagine the amount of labor I have to perform.
As an instance of what almost daily occurs, I will give you an
account of day-before-yesterdays duty. At early dawn, while
you, I hope, were quietly sleeping, I was up at Surgeons call
and before breakfast prescribed for 86 patients at the door of
my tent. After meal I visited the hospitals and a barn where
our sick are lying, and dealt medicines and write prescriptions
for one hundred more; in all visited and prescribed for, one
hundred and eighty-six men. I had no dinner. At 4 oclock
this labor was completed and a cold bite was eaten. After this,
in the rain, I started for Sharpsburg, four miles distant, for
medical supplies (17).
The soldiers diet consisted of fresh or pickled beef. It was

heavily salted and frequently needed to be soaked prior to cooking and was often spoiled. Salt-cured pork was often rancid and
mostly fat. Coee and hard tack were staples of the diet. Hard
tack was a large biscuit that was often dipped in coee to make
it more palatable. There was very little in the way of fresh fruits
or vegetables. Desiccated vegetables were often substituted, but
the process led to the loss of biologic activity of vitamin C and
unfortunately to many potentially preventable cases of scurvy.
Scurvy had been known to result from lack of fresh foods and
greens in the diet based on an observation made by Johann
Bachstrom in 1734. The case fatality rate of many diseases worsened as the war went on, perhaps as a result of malnutrition
and dietary deciencies.
The most common sickness among soldiers was gastrointestinal disorders. There were 711 cases per 1000 soldiers per
year (18). The rate was higher in the West, where sanitation was
worse. The mortality rate of acute diarrhea and dysentery was
3 to 17 per 1000 per year, while that of chronic diarrhea and
dysentery was 126 to 162 per 1000 per year (19). There were
no cholera outbreaks.
Malaria was also frequent: 224 of every 1000 Union soldiers
seeking medical treatment were diagnosed with the disease (20).
It was particularly common in southern states such as Arkansas
and Mississippi. William H. Van Buren discovered in 1861
that quinine could be used prophylactically to prevent malaria.
Southern states did not have a large enough supply to use it in
this way. Although the cause of malaria was unknown at the
time, it was known that its incidence could be reduced by locating camps away from stagnant water, sleeping in closed rooms,
and sleeping on elevated ground or upper oors of buildings.
Medical and surgical care during the American Civil War, 18611865
141
Digging ditches or canals and sleeping outdoors were known

to increase risk.
Yellow fever was a major problem in the South, killing over
10,000 people (21). There were more outbreaks in Texas during
the war than in any other state. Epidemics occurred in summer
and autumn months. It was known as the strangers disease
since it often aected newcomers to the area. Those that were
infected and survived acquired lifelong immunity. Outbreaks
would often occur after a ship arrived from a Caribbean port.
It could be prevented by quarantining newly arrived ships in
most cases. Attempts at its prevention by Benjamin Butler in
New Orleans may have been the rst example of a medical
incentive plan. Butler, with urging from his superior ocer
Rear Admiral David Farragut, told Dr. Jonathan M. Foltz: In
this matter your orders shall be absolute. Order o all you may
think proper [ships to quarantine], and so long as you keep
yellow fever away from New Orleans your salary shall be one
thousand dollars per month. When yellow fever appears in this
city your pay shall cease. Dr. Foltz quarantined all ships for
40 days 70 miles below the city, and this virtually eliminated
yellow fever in New Orleans (22).
There were over 75,000 cases of typhoid fever in the Union
Army during the war. It resulted from exposure to fecally contaminated food and water, as well as ies. It killed 17% of affected soldiers in 1861 and 56% by 1865 (23). Typhoid fever
was especially common in Washington, DC, where it claimed
the life of Abraham Lincolns son Willie.
Measles outbreaks were also common. There were at least
67,000 cases in the Union Army, with more than 4000 deaths.
Of the 1200 soldiers in the 12th North Carolina, 800 developed
measles during a 4-month period in 1861 after arriving in a
West Virginia camp (24). Farmers made up 48% of the Union
Army, and rural populations often had very little immunity to
childhood diseases. Epidemics were common at the time of an
inux of new troops, especially early in the war. The death rate
was almost twice as high in African Americans as in whites,
11% versus 6%.
A smallpox vaccine had been invented by Edward Jenner 70
years before the war, but a large percentage of the population
was not vaccinated. The annual incidence of smallpox was 5.2
cases per 1000 in whites and 35.1 per 1000 in African Americans (25). Cases were quarantined. Because vaccine material
was in short supply during the war, material was aspirated from
the pustules of vaccinated people. This unfortunately resulted
in the transmission of many cases of syphilis.
142
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org/education/civil-war-casualties.html.
Hacker JD. A census-based count of the Civil War dead. Civ War Hist
2011;57:307348.
Foote S. The Civil War: A Narrative, vol. 3. New York: Random House,
1958:10401041.
Grace W. The Army Surgeons Manual: For the Use of Medical Ocers,
Cadets, Chaplains, and Hospital Stewards: Containing the Regulations of
the Medical Department, All General Orders from the War Department, and
Circulars from the Surgeon-Generals Oce from January 1st, 1861 to April
1st, 1865. New York: Bailliere Brothers, 1865. Available at http:archive.
org/stream/62510310R.nlm.nih.gov/62510310R_djvu.txt.
Blanton D, Cook LM. They Fought Like Demons: Women Soldiers in the
Civil War. New York: Random House, 2002:7.
Freeman FR. Gangrene and Glory: Medical Care During the American Civil
War. Urbana, IL: University of Illinois Press, 1998:2829.
Wilbur CK. Civil War Medicine. Guilford, CT: Global Pequot Press,
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Mitchell SW. On the medical department in the Civil War. JAMA
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Rutkow IM. Bleeding Blue and Gray: Civil War Surgery and the Evolution
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Adams GW. Doctors in Blue: The Medical History of the Union Army in the
Civil War. Baton Rouge, LA: Louisiana State University Press, 1952:26.
Beller SP. Medical Practices in the Civil War. Charlotte, VT: OurStory,
1998:5762.
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Press, 2002:223.
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Knoxville, TN: University of Tennessee Press, 1983:3.
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www.civilwarhome.com/sedgwickdeath.htm
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1867;2:246248.
Holmes OW. Currents and Counter-Currents in Medical Science with Other
Addresses and Essays. An Address Delivered Before the Massachusetts Medical
Society at the Annual Meeting, May 30, 1860. Cambridge, MA, University
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M.D. Kent, OH: Kent State University Press, 1994:34.
Adams GW: 226.
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Bell AM. Mosquito Soldiers: Malaria, Yellow Fever and the Course of the
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Volume 29, Number 2
Exercise-induced acute compartment syndrome in a young

man, occurring after a short race
Bibhusan Basnet, MD, Mousa Matar, MD, Siddharthan Vaitilingham, MD, Shyam Chalise, MD, Nkem Irooegbu, MD, MPH,
and Jane Bang, MD
We describe a case of exercise-induced acute compartment syndrome

(ACS) in a 23-year-old man who presented to his primary care physician
48 hours after he attempted to run a 5K race. He noticed searing pain
in his left leg after the first half mile but had no other symptoms. He was
referred to the emergency department and diagnosed with ACS, and a
fasciotomy was done. A presentation of limb pain that is out of proportion to a known or suspected injury should prompt consideration of ACS.
Early recognition and surgical management are essential to achieving
the best possible outcome.
cute compartment syndrome (ACS) is an emergency

requiring immediate surgical decompression (1). Because it can progress rapidly, urgent diagnosis and
treatment are necessary to prevent subsequent tissue
ischemia and necrosis. The syndrome is typically a consequence of trauma (2). Chronic compartment syndrome is a
common problem among athletes, while an acute presentation
after exercise is rare (37). Our case demonstrates delayed
presentation of exercise-induced ACS.
CASE PRESENTATION
A 23-year-old man with no signicant medical history presented to his primary care physician with severe pain in the left
lower leg. Two days earlier, he attempted to run a 5K race but
had to stop after the rst half mile. He complained of searing pain associated with numbness in his left lower extremity.
He described some pain in his right leg as well, but of a less
severe nature. He stopped running with the onset of pain and
attempted to resume after stretching but was unable to do so due
to his pain. Rest, warm and cold compresses, acetaminophen,
and nonsteroidal antiinammatory drugs did not alleviate the
pain. On examination, he had signicant swelling and tenderness in the anterior and lateral aspects of his left leg. Distal
pulses were palpable in both legs. He was sent to the emergency
department for further evaluation.
Radiographs taken in the emergency department showed
no bony injury or other abnormality. Doppler venous ultrasound revealed no evidence of deep vein thrombosis. His serum creatine kinase was 15,988 U/L (normal range, 30233);
aspartate aminotransferase, 348 U/L (normal range, 1359);
alanine aminotransferase, 164 U/L (normal range, 753); and

creatinine, 1.19 mg/dL (normal range, 0.71.3). Compartment
pressures in the leg were obtained using a commercially available intracompartmental pressure monitor system and found to
be 50 in the anterior and lateral compartment with a delta pressure of <30. A left anterior and lateral fasciotomy was performed
within 6 hours of initial presentation. No muscle rupture was
found intraoperatively. Aggressive intravenous uid therapy
was initiated to treat his rhabdomyolysis. Postoperatively, the
patient's symptoms improved rapidly and his serum creatine
kinase quickly improved. Two days later, secondary closure of
the skin overlying the fascial releases was performed. The patient
was discharged home after a 3-day stay.
DISCUSSION
ACS is a limb-threatening and occasionally life-threatening
condition characterized by increased interstitial pressure within
an osteofascial compartment, exceeding a critical point and
resulting in reduced tissue perfusion and myoneural ischemia
(8). ACS has been reported after heavy exercise, weight lifting,
military training, and marathons (810). Our patient had leg
pain after a very short run. The dierential diagnosis included
compartment syndrome, muscle group rupture, stress fracture,
and ligament injury. We used a noninvasive test to determine
compartment pressure. A recent metaanalysis suggested use of
intracompartmental pressure measurement to conrm the diagnosis in patients in whom ACS is suspected (11). Magnetic
resonance imaging of the leg would have helped with the preliminary dierentials, but with an elevated delta pressure of the
lower extremity, ACS was considered and emergency fasciotomy
was done.
ACS should be especially suspected in the presence of one
or more of the following symptoms: pain out of proportion to
a known or suspected injury (with or without pain on passive
stretch), sensory changes, and a loss of motor power (12).
In our patient, ACS is likely to have occurred secondary
to exercise-induced rhabdomyolysis resulting in tissue edema
From the Presence St. Joseph Hospital, Chicago, Illinois.
Corresponding author: Bibhusan Basnet, MD, Department of Internal Medicine,
Presence St. Joseph Hospital, 2900 N. Lakeshore Drive, Chicago, IL 60657
(e-mail: bibhusan117@gmail.com).
143
with subsequent muscle injury and tissue damage. Some cases

of exercise-induced compartment syndrome may evolve over a
prolonged period of time, with slow but progressive muscle tissue injury. The fascia that delineates the compartments prevents
expansion, causing a rise in the intracompartmental pressures
(13).This can cause further elevations in creatine kinase, which
can lead to severe acute kidney injury, electrolyte abnormalities,
and permanent muscle damage. In our patient, the creatine
kinase level was elevated to >10,000 without evidence of acute
kidney injury or myoglobin in urine.
Rhabdomyolysis must be considered in patients presenting with ACS so that early compartment release surgery and
vigorous uid resuscitation can be initiated. Elevated serum
transaminases were also noted at presentation, a nding that
improved in parallel to the creatine kinase levels. The patient
had no high-risk behavior, and serology for hepatitis viruses
was negative. Skeletal muscle injury is believed to be the most
likely source of the elevated transaminases.
ACS is diagnosed on the basis of clinical ndings. In highrisk patients, surgical consultation, possibly including the measurement of compartment pressures, should not be delayed in
order to obtain laboratory test results. A delta pressure (compartment pressure subtracted from diastolic blood pressure)
of <30 mm Hg indicates a need for fasciotomy (14). Serial or
continuous measurements are essential when patient risk or
clinical suspicion is high.
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Hill CE, Modi CS, Baraza N, Mosleh-Shirazi MS, Dhukaram V.
Spontaneous compartment syndrome of the foot. J Bone Joint Surg Br
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Hope MJ, McQueen MM. Acute compartment syndrome in the absence
of fracture. J Orthop Trauma 2004;18(4):220224.
Nau T, Menth-Chiari WA, Seitz H, Vcsei V. Acute compartment syndrome
of the thigh associated with exercise. Am J Sports Med 2000;28(1):120122.
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syndrome. A report of two cases. Clin Orthop Relat Res 1992;(284):189192.
Miozzari HH, Gerard R, Stern R, Toman J, Assal M. Acute exertional
medial compartment syndrome of the foot in a high-level athlete: a case
report. Am J Sports Med 2008;36(5):983986.
Shadgan B, Menon M, OBrien PJ, Reid WD. Diagnostic techniques in acute compartment syndrome of the leg. J Orthop Trauma
2008;22(8):581587.
Shadgan B, Menon M, Sanders D, Berry G, Martin Jr C, Duy P, Stephen
D, OBrien PJ. Current thinking about acute compartment syndrome of
the lower extremity. Can J Surg 2010;53(5):329334.
King TW, Lerman OZ, Carter JJ, Warren SM. Exertional compartment
syndrome of the thigh: a rare diagnosis and literature review. J Emerg
Med 2010;39(2):e93e99.
McQueen MM, Gaston P. Acute compartment syndrome. Who is at risk?
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Volume 29, Number 2
Table tipping and a near-miss fall after unlocking a surgical

table holding a morbidly obese patient
Robert T. Booth, MD, Russell K. McAllister, MD, and Timothy M. Bittenbinder, MD
Presented is a case report of a morbidly obese patient who experienced

a near-miss fall in the operating room due to several factors. We present the importance of recognizing the change in fulcrum location on a
Steris 4085 operating table when the bed is in the unlocked versus the
locked position. This small change, in the presence of morbid obesity and
reverse orientation of the table, can lead to an unsafe situation in which
the patient's weight can cause the table to tip. We present potential ways
to avoid this complication.
he prevalence of obesity for adults in the United States

more than doubled from 1960 to 2010. In addition,
the prevalence of those qualifying as extremely obese
increased sixfold in that same time period (1). Not only
have we experienced a signicant increase in patient weight, but
caring for an increasingly obese population has led to a worsening of the economic burden. The medical cost of obesity nearly
doubled over the 10-year period from 1998 to 2008, rising from
$78.5 billion to $147 billion (2). Obese patients are not only
susceptible to the physiologic and pathological risks associated
with their body habitus, but approach the limits of the safe use
of operating room (OR) equipment, further increasing their risk
of morbidity and mortality in the operative suite. We present
a case of a near-miss fall of a morbidly obese patient occurring
when the OR table tipped after unlocking stabilizing pistons
in order to move the table position.
CASE DESCRIPTION
A 41-year-old man with chronic sinusitis presented to the
operative suite for endoscopic nasal surgery. He was 63 (1.9
m) and 417 lbs (189 kg), with a body mass index (BMI) of
52.4, placing him in the superobese category of obesity (BMI
>49.9). The patient was transferred to the Steris 4085 (Steris
Corporation, Mentor, OH) OR table, with the OR table in
reverse orientation and the full articulation slide of the tabletop
away from the base toward the direction of the patients head
(Figure 1). General anesthesia was induced, and the patient was
endotracheally intubated uneventfully. The surgeon then requested that the OR table be turned 90 degrees to the patients
left to improve access to the operative site and enable use of image guidance equipment. The circuit was disconnected from the
Figure 1. Steris 4085 operating room table in the reverse position.
endotracheal tube, and the operating table was unlocked. The

table began to abruptly tip downward with the patient's head
rapidly approaching the oor in a Trendelenburg-like trajectory. Fortunately, the resident was at the head of the table and
was able to slow the table from tilting further, while another
person provided counterweight at the foot of the table to level
and stabilize it. The table was then turned with an adjustable
height stool under the head of the table and additional sta
placing counterweight at the foot of the table to maintain a
level position. Once the OR table was relocked, the stool was
kept in place to safeguard against a subsequent tipping. The
patient did not experience any adverse eects from the event
and the decision was made to proceed with the surgery as
planned. The rest of the case was completed without incident
or complication.
DISCUSSION
Unfortunately, it isnt dicult to nd examples in the news
of patient falls in the OR leading to tragic, and sometimes lethal,
results (3, 4). Often, these falls are a result of lack of attentiveness by OR sta during at-risk times, such as after the security belt has been removed during emergence from anesthesia
From the Department of Anesthesiology, Baylor Scott & White Health, Temple,
Texas.
Corresponding author: Russell K. McAllister, MD, Department of Anesthesiology,
Baylor Scott & White Health, 2401 South 31st Street, Temple, TX 76508 (e-mail:
rmcallister@sw.org).
145
(4). Additionally, a case similar to ours described a morbidly

obese patient presenting for nasal surgery, who nearly fell from
a tipping OR table after it was unlocked (5). An inquiry of
the Anesthesia Closed Claims Project Database since the year
2000 revealed 21 claims in which a patient fell from the OR or
procedure table. Fifteen of the scenarios were related to general
anesthesia; four involved scenarios of regional anesthesia, and
two, monitored anesthesia care (2). Most of the falls resulted
in temporary and nondisabling injuries, but two resulted in
permanent and severe injury. Among the 21 patient falls, half
resulted in payment to the plainti ranging from $18,000 to
$925,000, with a median payment of $49,000 (personal correspondence, Karen Posner, PhD, December 10, 2015).
The Steris 4085 OR table allows the tabletop to slide away
from the base, thereby freeing space underneath the patient for
radiologic imaging equipment. Examination of the product
specication sticker on the OR table regarding weight limits
by table position could easily lull a provider into a false sense
of security. The stickers reveal a diagram of the OR table in
normal orientation with the slide mechanism fully articulated
toward the head with a stated weight limit of 600 lbs. Further
investigation of the manufacturers sales literature reveals that
the weight parameters are accurate in the normal orientation,
without specifying limits in the reverse orientation position
(6). It is important to note the manufacturers warning to not
release the oor locks while the patient is on the table. One
factor behind this warning is the shifting of the fulcrum once
the leveling oor lock pistons are raised to lower the OR table
onto the wheels in order to mobilize the table. In the case of
the Steris 4085, unlocking the OR table shifts the fulcrum 4.75
inches toward the feet, eectively shortening the base when the
oor lock pistons are withdrawn (Figure 2). Education of OR
personnel and vigilance by all OR sta can decrease the risk of
an OR table-tipping injury. OR personnel should be aware of
146
Figure 2. Close-up view of the base of the Steris 4085. Note the distance between
the wheels and the floor locking pistons and how it will affect the fulcrum when
the bed is unlocked and the wheels are engaged with the floor.
the potential dangers, and care should be taken to have needed

personnel readily available if the table needs to be unlocked
when a high-risk situation exists.
1.
2.
3.
4.
5.
6.
Fryar CD, Carroll MD, Ogden CL. Prevalence of overweight, obesity,

and extreme obesity among adults: United States, trends 19601962
through 20092010. NCHS Health E-Stat. Available at http://www.cdc.
gov/nchs/data/hestat/obesity_adult_09_10/obesity_adult_09_10.htm;
accessed January 2, 2016.
Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer- and service-specic estimates. Health
A (Millwood) 2009;28(5):w822w831.
Suit TD. Woman hurt after falling o operating table. Stamford Advocate,
May 22, 2012.
Irons ME. Family, hospital settle after mothers fatal fall in operating room.
Boston Globe, October 14, 2009.
Razavian S, Thurn J. On the tipping point of disaster: operating room
surgical table with obese patients. APSF Newsletter, 2013;28 2324.
Steris Corporation Steris 4085 Surgical Table: A Smart Investment in Surgical Versatility. Mentor, OH: Steris, 2010. Available at http://webapi.
steris.com/api/salesconnection/getdocumentbynumber?id=M3309EN&
leName=STERIS%204085%20SURGICAL%20TABLE:%20A%20
SMART%20INVESTMENT%20IN%20SURGICAL%20VERSATILITY.
pdf; accessed January 2, 2016.
Volume 29, Number 2
Use of ultrasound guidance to remove entrapped stimulating

popliteal catheters
Russell K. McAllister, MD, James B. Hulin, DO, and Don J. Daniels, MD
Peripheral nerve catheters are beneficial for continuous pain relief following surgery or trauma to an extremity. However, spring-loaded peripheral nerve catheters can become uncoiled and entrapped, resulting in
difficulty in catheter removal. We present two cases where ultrasound
guidance provided significant assistance in the safe removal of entrapped
peripheral nerve catheters without neurologic sequelae. One of the catheters was adhered to nearby tissue, and one had become uncoiled and
anchored in place by the distal tip. Guidelines for the safe management
of entrapped catheters are suggested, including the use of saline injections through the catheter under ultrasound guidance to assist in the
evaluation and removal of the catheters.
Figure 1. Distal tip configuration of Arrow StimuCath.
eripheral nerve catheters are typically easily removed

when the need for nerve blockade has ended. However, spring-loaded peripheral nerve catheters are at
risk for uncoiling with entrapment of the catheter and
wire in nearby structures. We report two cases of entrapped
catheters following popliteal nerve block utilizing a 20-gauge
catheter (Arrow StimuCath, Teleex Medical Germany, Kernen,
Germany) with a coiled omni-port end with a hemispherical
distal tip (Figure 1). Identication and removal of the catheters
was facilitated by the use of ultrasound. We report on the assessment and management of entrapped continuous peripheral
nerve catheters.
CASE 1
A 24-year-old American Society of Anesthesiologists class
I woman underwent a left tibiotalar arthrodesis under general anesthesia. The plan for postoperative analgesia included
the placement of a continuous popliteal nerve block. In the
postanesthesia care unit, a continuous popliteal catheter was
placed utilizing a lateral approach and ultrasound guidance.
A 17-gauge insulated needle was used to place a 19-gauge
60 cm StimuCath continuous nerve block catheter after obtaining nerve stimulation with dorsiexion at 0.55 milliamperes.
The catheter was secured with tape and attached to an elastomeric pump prior to discharging the patient home. On postoperative day 3, the patient was unable to remove the catheter
and presented for further evaluation. She denied any radicular
pain. The catheter insertion site was clean and dry, and the
patient had a normal lower extremity neurologic examination. An attempt to withdraw the catheter under ultrasound
visualization demonstrated lateral movement of the common
peroneal and tibial nerves. Injection of 10 mL of preservativefree normal saline through the catheter failed to relieve the
apparent adhesion. Lateral and anteroposterior x-rays of the
knee did not reveal a knot or kinking of the catheter (Figure 2).
A second attempt of injecting 20 mL of saline through the
catheter under ultrasound guidance successfully loosened the
catheter, resulting in its easy removal.
CASE 2
A 28-year-old man sustained a traumatic injury to his
right foot, requiring multiple surgeries including external
fixation and washouts. Ultimately, the patient underwent
a transmetatarsal amputation and opted for a continuous
popliteal nerve block for postoperative analgesia. In the preoperative holding area, a popliteal nerve block was placed
utilizing a posterior approach and ultrasound guidance. A
From Baylor Scott & White Health and Texas A&M College of Medicine, Temple,
Texas (McAllister, Daniels); and Integris Southwest Hospital, Oklahoma City,
Oklahoma (Hulin).
Corresponding author: Russell K. McAllister, MD, Assistant Dean, Quality and
Patient Safety and Residency Program Director, Department of Anesthesiology,
Baylor Scott & White Health, 2401 S. 31st Street, Temple, TX 76508 (e-mail:
rmcallister@sw.org).
147
Figure 2. Lateral knee radiograph revealing no obvious kinking or knotting of

the catheter.
17-gauge insulated needle was used to place a 19-gauge 60 cm

StimuCath continuous nerve block catheter after obtaining
nerve stimulation with dorsiexion at 0.50 milliamperes. The
catheter was secured and connected to an elastomeric pump
prior to discharge. On postoperative day 5, the patient was unable to remove the catheter and returned for further evaluation.
The catheter site was clean and dry with minimal erythema, and
the right lower extremity neurologic exam revealed no decits
in sensory or motor function. Ultrasound examination of the
popliteal fossa did not reveal movement of the neurovascular
structures when traction was placed on the catheter. However,
traction on the catheter did produce tenting under the skin
at the location of the distal tip of the catheter. This area was
prepped and draped in sterile fashion, and the skin was anesthetized with 3 mL of 1% lidocaine. Blunt dissection exposed
the metallic tip of the catheter, which was acting as an anchor.
Traction on the catheter had produced uncoiling of the distal
end. The hemispherical tip was cut from the end of the catheter
and removed through the incision site. Once the anchoring tip
was removed, the remaining portion of the catheter was easily
removed through the initial insertion site (Figure 3).
Figure 3. StimuCath catheter following removal in two parts reveals the uncoiled
distal end.
148
DISCUSSION
Complications from peripheral nerve catheters are rare but
important (13). These two cases demonstrate potential problems that may be encountered when using the Arrow StimuCath
system. Both cases resulted in entrapped peripheral nerve catheters. Wiesmann et al reported two similar cases of entrapped
stimulating catheters (4). In one of the cases, when the catheter
was unable to be removed with forceful traction, a surgical
removal was planned under general anesthesia. Once muscle
relaxation occurred, additional forceful traction on the catheter
allowed it to be removed intact without neurologic sequelae. In
the second case, additional force was used and the catheter was
removed intact. In both cases, the coiled ends of each catheter
had become uncoiled, as described in our patients.
To aid in the removal of entrapped peripheral nerve
catheters, we recommend the following approach:
Prior to attempting to remove the catheter, ensure full
sensation has returned to the limb.
Use ultrasound to identify the neurovascular bundle. If
traction on the catheter produces displacement of the
neurovascular structures, withhold traction.
Inject preservative-free normal saline through the catheter (hydrodissection) to loosen adhesions and reattempt
removal of the catheter under ultrasound visualization.
Inject contrast media through the catheter to rule out
catheter kinking or coiling.
Contact a surgeon for evaluation and possible surgical
removal.
The proposed mechanism for catheter entrapment in the
rst case was adhesions. Buckenmaier et al found that the manufactured design of a continuous peripheral nerve block tip can
contribute to adhesions in a rat model (5). They postulated that
removal of an adhered catheter could potentially cause neural
damage or injury to adjacent structures, including blood vessels.
The proposed mechanism of entrapment in the second case
was uncoiling of the spring-wound distal tip. Damage to the
spring-wound catheter tip during placement, most commonly
by shearing forces if the catheter is withdrawn back into the
needle, may increase the risk of uncoiling during removal, resulting in damage to nearby structures. Ultrasound was used
to evaluate the neurovascular bundle and revealed no evidence
of movement of the nerve complex when traction was placed
on the catheter. However, skin tenting by the uncoiled wire
catheter tip was noted within the tunnel site when traction on
the catheter was released.
We propose that ultrasound evaluation may oer advantages over plain x-ray in management of entrapped catheters.
Ultrasound allows visualization of the neurovascular structures,
whereas x-rays do not. In addition, the stimulating catheters with
the coil tips are visible with ultrasound, allowing identication
of catheter tip location. Most importantly, ultrasound visualization of these structures and their relationship to the catheter
tip during gentle traction and hydrodissection is not only
diagnostic, but in some cases may be therapeutic in relieving
adhesions. A similar technique has also been used to facilitate
removal of a knotted femoral nerve catheter that had become
Volume 29, Number 2
entrapped, theoretically by expanding the area just below the

fascia iliaca with 10 mL of saline. This increased area allowed
for easy removal of the knotted catheter (6). In addition, the
portability and simplicity of most ultrasound machines allows
for additional exibility. Ultrasound evaluation would also oer
a more feasible solution in patients with an allergy to intravenous contrast agents.
There have been no case reports to date revealing damage to
neurovascular structures upon removal of a continuous peripheral nerve catheter. However, the potential exists for damage,
and further study of the diagnosis and management of these
types of problems would be benecial.
1.
Borgeat A, Blumenthal S, Lambert M, Theodorou P, Vienne P. The feasibility and complications of the continuous popliteal nerve block: a 1001-case
survey. Anesth Analg 2006;103(1):229233.
April 2016
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De Tran QH, De La Cuadra-Fontaine JC, Chan SY, Kovarik G, Asenjo

JF, Finlayson R. Coiling of stimulating perineural catheters. Anesthesiology
2007;106(1):189190.
Cuvillon P, Ripart J, Lalourcey L, Veyrat E, LHermite J, Boisson C,
Thouabtia E, Jacques Eledjam J. The continuous femoral nerve block
catheter for postoperative analgesia: bacterial colonization, infectious rate
and adverse eects. Anesth Analg 2001;93(4):10451049.
Wiesmann T, Wallot P, Nentwig L, Beermann AV, Wulf H, Zoremba M,
Al-Dahna T, Eschbach D, Steinfeldt T. Separation of stimulating catheters
for continuous peripheral regional anesthesia during their removaltwo
case reports and a critical appraisal of the use of steel-coil containing
stimulating catheters. Local Reg Anesth 2015;8 1519.
Buckenmaier CCIII, Auton AA, Flournoy WS. Continuous peripheral
nerve block catheter tip adhesion in a rat model. Acta Anaesthesiol Scand
2006;50(6):694698.
Kendall MC, Nader A, Maniker RB, McCarthy RJ. Removal of a knotted
stimulating femoral nerve catheter using a saline bolus injection. Local
Reg Anesth 2010;3 3134.
Use of ultrasound guidance to remove entrapped stimulating popliteal catheters
149
Baclofen-responsive hiccups after esophageal stenting for

malignancy-related dysphagia
Vishal Sharma, DM, Arka De, MD, Sandeep Lamoria, MD, and Brinder Mohan Singh Lamba, MD
Hiccups can have multiple causes, including esophageal lesions. Hiccups

after insertion of self-expanding metallic stents have been reported occasionally following stenting for lesions of the gastroesophageal junction.
We report a patient who developed hiccups after insertion of a stent
for squamous cell carcinoma of the proximal esophagus. The hiccups
responded only to the initiation of baclofen therapy.
iccups or singultus refers to the sound produced by abrupt

closure of the glottis after repeated involuntary, spastic
contractions of the respiratory muscles. Hiccups are usually self-limited. The treatment options for persistent or
intractable hiccups are both pharmacological and nonpharmacological. Drugs reported to be useful include baclofen, gabapentin,
pregabalin, metoclopramide, domperidone, chlorpromazine, nifedipine, amitriptyline, valproate, carbamazepine, and phenytoin
(1). Nonpharmacologic treatments include hypnosis, acupuncture, nerve stimulation, and nerve blocks for vagus and phrenic
nerves (1). Hiccups related to placement of self-expanding metallic stent (SEMS) have been reported rarely in the literature (2, 3).
We report a case of persistent hiccups following placement of an
esophageal stent which responded to baclofen.
CASE REPORT
A 75-year-old man presented with progressively increasing
dysphagia to solid foods and weight loss for 3 months. Upper
endoscopy showed an ulceroproliferative mass about 20 cm
from the incisors, and the endoscope could not be negotiated
beyond the lesion. Biopsy revealed squamous cell carcinoma.
Chest computed tomography showed asymmetrical mural
thickening of the middle esophagus and loss of fat planes, with
the aorta and lesion abutting the carina. Using an ultrathin endoscope, the lesion length was assessed and an Ultraex partially
covered stent (15 cm) was placed across the lesion for palliation
of dysphagia. The immediate postendoscopic period was unremarkable. However, 12 hours after stent placement, the patient
developed hiccups that did not respond to physical maneuvers,
proton pump inhibitors, or chlorpromazine. His metabolic parameters, including liver and kidney function tests, creatinine,
and serum electrolytes, were normal. Chest radiographs conrmed the proper positioning of the stent and the absence of
pneumothorax or gas under the diaphragm. Repeat endoscopy
showed the stent in place and above the gastroesophageal junction. The patient was started on baclofen 5 mg three times daily
150
with good clinical response. Baclofen was given for 3 days and
then was stopped, with no recurrence of hiccups.
DISCUSSION
There are several known causes of persistent hiccups, including lesions of the reex arc, uremia, bronchoscopy, central line
placement, and cardiac pacing, as well as gastroesophageal reux
and esophageal obstruction or distension (1, 46). Expansion of
SEMS may lead to hiccups by producing esophageal distension,
or, in cases in which the gastroesophageal junction is stented,
through reux or diaphragmatic irritation (13). Chlorpromazine
is the only agent approved by the US Food and Drug Administration for the treatment of persistent hiccups (7). Although not
approved specically for this indication, baclofen, a centrally acting GABAB agonist, has been found to be eective in persistent
hiccups and may be considered in patients not responding to
chlorpromazine (8, 9). This is the rst report of a case in which the
esophageal stent produced baclofen-responsive hiccups, despite
the stent not crossing the gastroesophageal junction. We suggest
that stent-related hiccups may be treated with baclofen if they fail
to respond to physical maneuvers and chlorpromazine.
1.
2.
3.
4.
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Steger M, Schneemann M, Fox M. The pathogenesis and pharmacological

treatment of hiccups. Aliment Pharmacol Ther 2015;42(9):10371050.
Katsinelos P, Pilpilidis J, Xiarchos P, Christodoulou K, Papagianis A,
Amperiadis P, Eugenidis N. Baclofen therapy for intractable hiccups
induced by Ultraex esophageal endoprosthesis. Am J Gastroenterol
2000;95(10):29862987.
Turkyilmaz A, Eroglu A. Use of baclofen in the treatment of esophageal
stent-related hiccups. Ann Thorac Surg 2008;85(1):328330.
Fisher MJ, Mittal RK. Hiccups and gastroesophageal reux: cause and
eect? Dig Dis Sci 1989;34(8):12771280.
Kaufmann HJ. Hiccups: an occasional sign of esophageal obstruction.
Gastroenterology 1982;82(6):14431445.
Fass R, Higa L, Kodner A, Mayer EA. Stimulus and site specic induction
of hiccups in the oesophagus of normal subjects. Gut 1997;41(5):590593.
Chang FY, Lu CL. Hiccup: mystery, nature and treatment. J Neurogastroenterol Motil 2012;18(2):123130.
Walker P, Watanabe S, Bruera E. Baclofen, a treatment for chronic hiccup.
J Pain Symptom Manage 1998;16(2):125132.
Ramrez FC, Graham DY. Treatment of intractable hiccup with baclofen:
results of a double-blind randomized, controlled, cross-over study. Am J
Gastroenterol 1992;87(12):17891791.
From the Department of Gastroenterology, PGIMER and DR RML Hospital, Delhi,

India.
Corresponding author: Vishal Sharma, DM, Department of Gastroenterology,
PGIMER and Dr RML Hospital, Delhi, India (e-mail: docvishalsharma@gmail.com).
Specificity of testing in a cardiac rehabilitation setting

resulting in a patients return to high-intensity outdoor
activity following aortic dissection repair
Sparky Bartee, BS, Sanjay Shrestha, BS, Beatriz Ramos, BS, Tim Bilbrey, MBA, Pasquale Carbone, MS,
Jeffrey M. Schussler, MD, Rick Deutsch, MS, MBA, and Jenny Adams, PhD
A 66-year-old man who had undergone aortic dissection repair a year

earlier sought to assess the feasibility of returning to the high-intensity
outdoor activities he had long enjoyed. In response to his inquiry, the
cardiac rehabilitation staff at Baylor Hamilton Heart and Vascular Hospital
designed a comprehensive testing plan that simulated the specific movements and anticipated cardiac requirements associated with his goal
activities. The activities included 1) lifting and manipulating a 50-pound
suitcase, 2) hiking to the top of Half Dome in Californias Yosemite National
Park, and 3) scuba diving. To illustrate our approach, we describe some
of the tests that were performed and report the results. After analyzing
the detailed physiological data collected during testing, we provided the
patient with an exercise prescription and specific guidelines that he could
use to gauge his level of physical exertion during his outdoor adventures.
Within approximately 6 months of testing, he successfully performed the
goal activities without adverse symptoms.
year after undergoing successful repair of an acute

ascending aortic dissection, a 66-year-old man asked
his physician about returning to the high-intensity
outdoor activities he had long enjoyed prior to the
surgery. The patient, who wanted information about the feasibility of his goals, sought out the testing laboratory within
the Cardiac Rehabilitation Department at Baylor Hamilton
Heart and Vascular Hospital.
CASE REPORT
The patient had a history of hypertension, but he never used
tobacco, alcohol, or drugs and had no family history of aortic
dissection. He presented to his physician at the age of 64 with
a type A dissection (involving the innominate and left common
carotid arteries) in the setting of ascending aortic aneurysm.
Relevant medications upon arrival at our testing laboratory
2 years later included metoprolol, hydrochlorothiazide, aspirin,
and lisinopril. His body mass index was 23.8 kg/m2, and his
waist circumference was 35.5 inches. His preoperative ascending aorta measured 5.1 cm, and his postoperative aortic root
diameter measured 3.9 cm (normal range, 2.54.0 cm).
The patient posed a unique testing challenge for the sta
because he had three very dierent activity goals: 1) lifting and
manipulating a 50-pound suitcase, 2) hiking to the top of Half
Dome in Californias Yosemite National Park, and 3) scuba diving. Utilizing our facilitys specialized equipment, we designed
and implemented a comprehensive testing plan that would simulate the anticipated movements, force, and cardiac requirements
associated with these activities, enabling us to collect detailed
physiologic data. To illustrate our approach, we describe some
of the tests that were performed and the associated results.
In keeping with the standard protocol of our cardiac
rehabilitation facility, we used telemetry (TeleRehab VersaCare,
ScottCare Corp, Cleveland, OH) to monitor the patients electrocardiogram. His blood pressure was recorded at the beginning
and end of each session (before warm-up walking and after cooldown walking) and at peak exertion during the individual tests.
Testing was symptom limited, meaning that no specic blood
pressure or heart rate limits were used to restrict the patients
exercise intensity. We monitored him for elevated rate-pressure
product (systolic blood pressure heart rate 36,000) (1),
angina pectoris, dizziness, pain, arrhythmias, and shortness of
breath.
Goal 1: Lifting and manipulating a 50-pound suitcase.
To simulate lifting a suitcase and raising it overhead, the patient performed a deadlift and military press maneuver using
a static force gauge that was attached to a multidimensional
strength assessment system (IsoTrack Pro, JTECH Medical,
Midvale, UT) that measures static lifting, pulling, and pushing
strength. To simulate manipulation of the suitcase, the patient
performed the upright row, the bicep curl, and the military
press while wearing a noninvasive, continuous blood pressure
From the Department of Kinesiology, University of Texas at Arlington, Arlington,
Texas (Bartee, Shrestha, Ramos); the Cardiac Rehabilitation Department, Baylor
Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas (Bilbrey,
Carbone, Schussler, Adams); and the Division of Cardiology, Department of
Internal Medicine, Baylor University Medical Center at Dallas and Baylor Hamilton
Heart and Vascular Hospital, and Texas A&M College of Medicine, Dallas, Texas
(Schussler). Mr. Deutsch is a consultant in San Jose, California. Mr. Shrestha is
now with the Carter Rehabilitation and Fitness Center at Baylor All Saints Medical
Center, Fort Worth, Texas; Mr. Bartee is with the Food and Nutritional Supplement
Division of the US Food and Drug Administration, San Diego, California; and Ms.
Ramos is with the Cancer Foundation for Life, Dallas, Texas.
Corresponding author: Jenny Adams, PhD, Cardiac Rehabilitation Department,
Baylor Heart and Vascular Hospital, 411 N. Washington, Suite 3100, Dallas, TX
75246 (e-mail: jennya@BaylorHealth.edu).
151
Figure 1. Half Dome hiking tests and outcome: (a) a 45-degree cable pull to measure strength; (b) the stair-climber metabolic stress test, designed to simulate
the cable ascent to the summit of Half Dome in Yosemite National Park, California; and (c) the patient nearing the summit approximately 6 months after testing.
monitor (Finometer MIDI, Finapres Medical Systems B.V.,

Amsterdam, the Netherlands).
Goal 2: Hiking to the top of Half Dome (Figure 1). The
hike is 15 miles round trip with an elevation gain of 4737 feet;
the summit is 8842 feet above sea level. The nal 400 vertical
feet to the summit is a 600-foot stretch of smooth granite that
has a 45-degree incline and features waist-high cables that hikers
pull to move vertically.
To conrm the patients physiologic response to simulated
hiking, we had him complete a peak treadmill stress test while
wearing a calibrated desktop metabolic system (Fitmate MED,
Cosmed USA Inc., Chicago, IL) that directly measured his
oxygen consumption. An additional metabolic stress test was
needed to simulate the incline, duration, and diculty of the
cable ascent to the summit of Half Dome. We used a stairclimbing machine (StairMaster StepMill SM916, Nautilus Inc.,
Vancouver, WA) that had a built-in 45-degree slope and placed
it directly in front of resistance training equipment that had
a cable pull-down station. This set-up enabled the patient to
perform one-hand cable pulls while performing vertical stepping
movements. To ensure that the test accurately covered the goal
distance of 400 vertical feet, we measured the height of each step
a
and calculated the step rate accordingly. The protocol involved

2-minute stages that increased incrementally. The initial setting
was 24 steps per minute, and the patient ended the test at 71
steps per minute. He achieved 9 metabolic equivalents (METs,
dened as the energy cost of exercise, where 1 MET = 3.4 mL
O2 per kg of body weight per minute).
Goal 3: Scuba diving (Figure 2). We designed a series of
maneuvers to simulate a boat dive (i.e., walking to exit the boat,
entering the water, diving, and climbing back into the boat).
While wearing diving gear (a 35-pound tank and a 20-pound
weight belt), the patient completed ve repetitions of the following sequence: walking 15 feet toward a swimming pool, stepping
o to enter the water, swimming 164 feet, and climbing a ladder
to exit the pool. We measured his blood pressure, heart rate, and
breathing frequency immediately after each sequence. Because
systolic and diastolic pressures return to normal approximately
10 seconds after the last repetition of a resistance training set
(2), we placed the blood pressure cu on the patients arm immediately after he exited the pool.
Peak heart rate, systolic blood pressure, and rate-pressure
product data obtained during tests corresponding to each of
the patients goals are shown in the Table. The peak breathing
Figure 2. Scuba diving tests and outcome: (a) exiting the pool after a simulated diving sequence; (b) staff members measuring vital signs; and (c) the patient diving
in Cozumel, Mexico, approximately 5 months after testing.
152
Volume 29, Number 2
Table. Peak heart rate, systolic blood pressure, and rate-pressure

product data from selected tests designed to simulate the
physiologic exertion of the patients goal activities
Test and related goal activity
HR (bpm) SBP (mm Hg)
RPP
Static strength exercises*

For suitcase manipulation:
Upright row
94
147
13,818
Bicep curl
92
155
14,260
74
154
11,396
178
170
30,260
Stair-climber metabolic stress test

for Half Dome hiking
131
158
20,698
Pool simulation of scuba diving with

tank and belt (55-lb load)
105
138
14,490
Military press
For Half Dome cable:
45-degree pull
*Data shown for right arm.

Measured with a continuous blood pressure monitor instead of a cuff.
HR indicates heart rate; SBP, systolic blood pressure; RPP, rate-pressure product.
frequency during the Half Dome and scuba diving tests was 36
breaths per minute, and the peak rating of perceived exertion
was 7 on a scale of 1 to 10, signifying really hard eort. During the 3 days of exercise testing, the patient had no adverse
signs or symptoms that required him to discontinue any session.
DISCUSSION
Aortic dissection has been linked with severe physical exertion (3), and disproportionate mean arterial blood pressure
responses (320/250 mm Hg) have been associated with heavy resistance training and the Valsalva maneuver (4). Individuals who
have survived aortic dissection often struggle with functional
independence (5), and they may fear reaching the intensity that
would be required for their return to strenuous activities. The
reality, however, is that patients who are physically active before
their cardiovascular event or surgery want to resume performing
exercise at the intensity levels they are accustomed to.
Exercise guidelines for those who have had aortic dissection repair are vague and inconsistent (3, 58). The patient in
this case, for example, was given the following recommendations: aerobic exercise is permissible, but lifting anything over
30 pounds is not; systolic blood pressure should not exceed
160 mm Hg; and resistance training should be limited to low
amounts of weight and high numbers of repetitions. Furthermore, he was advised to avoid straining by breath holding (the
Valsalva maneuver), as during bowel movements. The drawback
to any limited prescription for exercise after surgery is that it is
based on little, if any, scientic data.
At our specicity of testing laboratory, we develop physical
performance tests that are designed to simulate the patients
activity goals. We then use the physiologic data collected during
testing to create a biofeedback model through which we are able
to provide specic exercise guidelines. In this case, we provided
April 2016
data about his breathing frequency, heart rate, and rating of

perceived exertion that he could use to more accurately gauge
the intensity level of physical exertion during his activities. Although our simulated testing approach provides no guarantee
against future cardiovascular events, our goal was to provide
this patient research-based objective exercise recommendations,
which are clearly needed in this at-risk population.
Nevertheless, the fact that no cardiovascular event occurred
during the simulated testing does not substantiate that the activities are safe. Simulated testing also has an inherent limitation that
must be noted. Additional stressors (emotional, environmental,
altitude, etc.) that cannot be eectively replicated in a laboratory
may result in increased cardiac demand when patients perform
the goal activities in their routine environmental setting.
Approximately 18 months after undergoing aortic dissection repair, the patient reached his goals without cardiovascular
symptoms. He uneventfully carried his 50-pound suitcase on
a trip to Cozumel, Mexico, where he performed 16 dives. A
month later, he hiked to the top of Half Dome.
Acknowledgments
Grant support was provided by an anonymous foundation
and the Baylor Health Care System Foundation, Dallas, Texas,
through the Cardiovascular Research Review Committee and in
cooperation with the Baylor Heart and Vascular Institute. The
authors thank the Cardiovascular Research Review Committee for their continued support of cardiovascular rehabilitation
research projects. Beverly Peters, MA, ELS, a freelance medical
editor, assisted with manuscript development and preparation.
1.
2.
3.
4.
5.
6.
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8.
Adams J, Cline MJ, Hubbard M, McCullough T, Hartman J. A new

paradigm for post-cardiac event resistance exercise guidelines. Am J Cardiol
2006;97(2):281286.
MacDougall JD, Tuxen D, Sale DG, Moroz JR, Sutton JR. Arterial blood pressure response to heavy resistance exercise. J Appl Physiol
1985;58(3):785790.
Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades
JA. Weight lifting and aortic dissection: more evidence for a connection.
Cardiology 2007;107(2):103106.
1985;58(3):785790.
Chaddha A, Kline-Rogers E, Woznicki EM, Brook R, Housholder-Hughes
S, Braverman AC, Pitler L, Hirsch AT, Eagle KA. Cardiology patient page.
Activity recommendations for postaortic dissection patients. Circulation
2014;130(16):e140142.
Williams MA, Haskell WL, Ades PA, Amsterdam EA, Bittner V, Franklin
BA, Gulanick M, Laing ST, Stewart KJ; American Heart Association
Council on Clinical Cardiology; American Heart Association Council
on Nutrition, Physical Activity, and Metabolism. Resistance exercise in
individuals with and without cardiovascular disease: 2007 update. Circulation 2007;116(5):572584.
Chaddha A, Eagle KA, Braverman AC, Kline-Rogers E, Hirsch AT, Brook
R, Jackson EA, Woznicki EM, Housholder-Hughes S, Pitler L, Franklin
BA. Exercise and physical activity for the post-aortic dissection patient:
the clinicians conundrum. Clin Cardiol 2015;38(11):647651.
Chaddha A, Kline-Rogers E, Eagle KA, Braverman AC, Erickson SR,
Jackson EA, Franklin BA, Woznicki EM, Jabara JT, Montgomery DG,
Eagle KA. Survivors of aortic dissection: activity, mental health, and sexual
function. Clin Cardiol 2015;38(11):652659.
Specificity of testing in a cardiac rehabilitation setting resulting in a patients return to high-intensity outdoor activity
153
Invited Commentary
Simulated performance testing to determine the aortic dissection patients
potential for vigorous physical activity
cute aortic dissection (AD) is a life-threatening emergency that involves a tear in the intimal-medial wall and
occurs predominantly in adults with systemic hypertension (13). The hypothesized mechanisms responsible
for the development and triggering of AD are shown in Figure 1
(3). Despite recent advances in the acute treatment and medical
management of AD, in-hospital mortality for patients with AD
remains high, regardless of the type of dissection (i.e., involving
Figure 1. Schematic of hypothesized mechanism of acute aortic dissection.
the ascending aorta [type A] or distal to the left subclavian artery
MMPs indicates matrix metalloproteinases; SBP, systolic blood pressure. Adapted
[type B]) (4). Nevertheless, survival rates in patients presenting
from Hatzaras et al., 2007 (3).
with type A AD treated with surgery approximate 96% and
91% at 1 and 3 years versus 89% and 69% for those managed
medically (5).
except at the highest levels of exertion, at which SBPs between
Although progressive acute management has contributed
180 and 220 mm Hg may be achieved in some persons (8).
to the improved prognosis, survivors of acute AD maintain
In contrast, heavy weight lifting, which may transiently evoke
a heightened risk of aortopathy and associated cardiovascular
excessive increases in SBP (>300 mm Hg) (1013), has been
events that may be favorably or unfavorably modulated by carsuggested as the trigger for AD in numerous reports (1416).
dioprotective interventions and selected triggers, respectively
Consequently, it seems reasonable for post-AD patients to avoid
(Figure 2) (6). Because few data are available regarding the spestrenuous weightlifting performed to failure or lifting heavy
cic types and intensities of exercise that may be both safe and
objects to decrease the risk for future aortic dilation, dissecbenecial for this escalating patient population, this void poses a
tion, and/or aortic rupture (6). For individuals with known
conundrum for patients with a prior AD, as well as for clinicians
aortic dilation, it appears that lifting up to 50% of their body
caring for and counseling them. Consequently, following AD,
weight during the bench press or an equivalent level of perceived
physical inactivity and depression/anxiety generally increase,
exertion for other strength exercises is relatively safe, provided
which further reduce functional capacity and/or quality of life
that the peak SBP remains below 200 mm Hg (8, 16). For
in AD survivors (7).
Understanding the hemodynamic responses to varied types of physical activity (8), as well as the role of commonly
prescribed antihypertensive agents (e.g.,
-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor
blockers), to attenuate average and peak
systolic blood pressures (SBP) during
physical exertion, potentially allowing
the AD survivor to more safely tolerate
greater intensities of exercise, is crucial to
preventing recurrent cardiac events in this
high-risk patient population while simultaneously maintaining or improving their
functional capacity, self-ecacy, and psychosocial well-being (6, 9). Aerobic exer- Figure 2. Potential triggers and cardioprotective interventions for acute aortic dissection. ACE indicates
cise elicits only a modest rise in SBP (10 angiotensin-converting enzyme; ARB, angiotensin receptor blocker. Reprinted with permission from Chaddha
mm Hg/metabolic equivalent [MET]), et al, 2015 (6). Copyright Wiley Periodicals, Inc.
154
post-AD patients, even more conservative SBP upper limits

(e.g., 160170 mm Hg) would appear prudent.
Because structured aerobic exercise lowers the product of
the heart rate (HR) and SBP at rest and at any given level of
submaximal exercise, signifying a reduction in the rate-pressure
product, a key determinant of myocardial oxygen consumption (r = 0.92) (17, 18), it is feasible that exercise regimens
might lower lifelong recurrent aortic risk during exertion-related
and nonexertion (e.g., emotional) stresses. Since -blockers
are associated with improved survival in patients with prior
AD, presumably by reducing HR, myocardial contractility, and
abrupt increases in ventricular pressure (9), it is plausible that
regular exercise may also serve as a cardioprotective intervention for the AD patient (6). Moreover, the associated increase
in cardiorespiratory tness has also been shown to be a strong
prognostic indicator, inversely related to cardiovascular and allcause mortality in patients with and without heart disease (19).
The prognosis of the AD patient has considerably improved
over the last decade by advances in rapid diagnosis, medical
therapies, and emergency surgery. To counter the adverse sequelae associated with the surgical approach, including deconditioning, reduced functional capacity, and decreased quality
of life, cardiologists and cardiovascular surgeons increasingly
refer these patients to medically supervised, exercise-based
cardiac rehabilitation programs. These centers are designed to
rehabilitate patients through electrocardiographically (ECG)
monitored exercise therapy and complementary counseling and
education, simultaneously providing referring physicians with
valuable serial surveillance data to potentially enhance their
ongoing medical management. In a cohort of 33 French patients (25 men, 8 women) with AD (mean SD age = 55.1
9.3 years), moderate-intensity rehabilitative exercise sessions (18
10) were carried out on a cycle ergometer at 11.3 1.5 (fairly
light) using the 6 to 20 category Borg scale, with blood pressure
monitoring during training (<160 mm Hg in 75% of patients).
Physical work capacity during cycle ergometer testing increased
from 62.7 11.8 to 91.6 16.5 watts (P = 0.002). Follow-up
was for 1 year and included 3 complications in 2 patients that
required additional thoracic surgery, although no deaths, cerebrovascular accidents, or myocardial infarctions were recorded.
Ten of the 19 patients (53%) of working age were able to return
to work (20). These data substantiate the feasibility, relative
safety, and eectiveness of exercise-based cardiac rehabilitation
in post-AD survivors.
For selected AD patients, returning to former occupational
and leisure-time activities is an important objective and may
also be psychologically therapeutic. Unfortunately, many of
these patients fail to return to specic activities, including sexual
activity (7), because they lack the medical assurance that they
can resume these activities safely. Because advising the post-AD
patient to return to high-volume, high-intensity activities is
complex, it is important for physicians (and patients) to have as
much information as possible about the associated myocardial
and aerobic requirements. The underlying assumption for a
safe return to activity is that the AD patient should work below
April 2016
loads that evoke abnormal clinical signs or symptoms, including ischemic ST-segment depression, angina pectoris, serious
arrhythmias, or excessive HR and/or SBP responses. Moreover,
the associated energy expenditure should be considerably less
than the patients peak or symptom-limited functional capacity.
Several noninvasive procedures can be used in formulating a
prescription for activity resumption. These may involve a clinical assessment of the patient and activity simulation, including
an analysis of the type of work, cardiac demands, and energy
requirements. Testing may include weight carrying, repetitive
weight lifting, arm wrench work, machine operation, or combinations thereof, using ambulatory ECG and blood pressure
monitoring. Although conventional exercise testing is still the
most widely used technique to evaluate exertion-related hemodynamic responses, aerobic capacity, and associated ECG
changes during progressive physical activity, standard lower
extremity exercise may not necessarily reect the requirements
for lifting and carrying.
In the current issue of the Baylor University Medical Center
Proceedings, Bartee et al (21) provide an interesting case report
on a 66-year-old man who underwent AD (type A) repair 18
months earlier and, by undergoing a series of simulated physical performance tests designed to mimic the vigorous to high
intensity physical activities that he wanted to return to, he was
able to accomplish these uneventfully.
The patients activity goals were varied and included lifting
and manipulating a 50-pound suitcase, hiking to the top of Half
Dome in Californias Yosemite National Park, and scuba diving.
Cardiac rehabilitation sta developed an ingenious, comprehensive series of tests that simulated the anticipated physical, static,
aerobic, and myocardial requirements of these activities, as illustrated and described (21). Testing was symptom-limited, and
no specic HR or SBP limits were used to restrict the patients
exercise intensity. The HR responses during the 6-test battery
averaged 112 bpm, corresponding to 73% of the patients agepredicted HR max, whereas SBPs were generally compatible
with conventional endurance training regimens, ranging from
138 to 170 mm Hg. Clearly, the 45-degree cable pull-down
station, associated with the stair climber metabolic stress test to
simulate Half Dome hiking, elicited the highest rate-pressure
product, 30,260 mm Hg bpm. Nevertheless, these attenuated hemodynamic responses were most likely attributed to the
patients aggressive medical management, including -blocker,
diuretic, and angiotensin-converting enzyme inhibitor therapy.
The patient completed the entire test battery without adverse symptoms, and the objective data obtained, including perceived exertion, were used to provide specic exercise guidelines
that enabled him to safely achieve his real-life activity goals.
The authors acknowledged that uneventful simulated testing
does not substantiate that such activities are invariably safe,
and that additional unaccounted for superimposed stressors,
including environmental factors, altitude, and the hyperadrenergic response associated with competition, could further
exacerbate the associated cardiac demands. Despite these limitations, the present case report underscores the importance of
Simulated performance testing to determine the aortic dissection patients potential for vigorous physical activity
155
further dening and expanding the exertional parameters of the

post-AD patient, using activity simulation to help rectify the
current vagaries in the prescriptive process.
Barry A. Franklin, PhD
Department of Preventive Cardiology and
Cardiac Rehabilitation
William Beaumont Hospital, Royal Oak, Michigan
Oakland University William Beaumont School of Medicine,
Rochester, Michigan
E-mail: Barry.Franklin@beaumont.org
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the clinicians conundrum. Clin Cardiol 2015;38(11):647651.
Chaddha A, Kline-Rogers E, Braverman AC, Erickson SR, Jackson EA,
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Volume 29, Number 2
Cardiovascular autonomic neuropathy

Niamh McCarty and Barry Silverman, MD
Cardiovascular autonomic neuropathy often goes unrecognized. We present a case of a 22-year-old man with multiple manifestations of this
disease, including weakness, dizziness, fatigue, tachycardia, abnormal
QTc, and orthostasis, which occurred 2 years after his type 1 diabetes
diagnosis. He exhibited parasympathetic denervation with resting tachycardia and exercise intolerance but also had evidence of orthostatic
hypotension, which suggests sympathetic denervation. He did not have
complete cardiovascular autonomic reflex testing, which would have
been helpful, but improved with aggressive diabetes treatment and the
increase of beta-blockade. It is important to identify these patients to
understand their signs and symptoms and consider appropriate therapies.
ardiovascular autonomic neuropathy (CAN) is a serious

and common complication of diabetes mellitus (DM)
that is often not recognized. Diabetes mellitus aects
more than 26 million people in the United States. Prevalence rates of CAN increase with age and duration of DM. The
Diabetes Control and Complication Trial reported rates as high
as 35% in type 1 DM and 44% in type 2 DM, with a prevalence
rate of up to 60% in longstanding diabetics (1). The presence
of CAN is associated with increased cardiovascular mortality
and is the cause of cardiac dysfunction and multiple clinical
symptoms, including resting tachycardia, exercise intolerance,
postural hypotension, silent ischemia, cardiomyopathy, and
perioperative instability (14).
CASE REPORT
A 22-year-old African American man with a 2-year history
of type 1 DM presented to the clinic with complaints of fatigue, decreased exercise tolerance, palpitations, and persistent
tachycardia. He was 6' tall and 147 lb. His blood pressure and
heart rate recorded supine, sitting, and standing after 3 minutes
were 138/80 mm Hg/105 beats per minute (bpm), 130/88
mm Hg/122 bpm, and 98/72 mm Hg/126 bpm, respectively.
His exam revealed the presence of peripheral neuropathy with
numbness and tingling extending bilaterally to the shin. A
Holter monitor recorded a marked decrease in his heart rate
variability (HRV), with HRV of 20 bpm over each hour and an
average of 118 bpm with no dipping during sleep. His thyroid
function was normal. An electrocardiogram exhibited sinus
tachycardia, a borderline abnormal QTc interval of 448 ms, a

QT of 324 ms, ST elevation in all leads, and 38 mm voltage in
V5. The echocardiogram demonstrated an ejection fraction of
45% to 50%, mild septal bounce, and left ventricular diastolic
abnormality. A cardiac nuclear study reported an ejection fraction of 37% with global hypokinesis. His hemoglobin A1c level
was 10.7%, with a history of poorly controlled blood sugars. His
medications at the time of the clinic visit included metoprolol
succinate 50 mg daily, insulin therapy, and gabapentin. Once
CAN was diagnosed, the patient improved with aggressive treatment of his diabetes, which lowered his hemoglobin A1c to <7,
and the increase of beta-blockade.
DISCUSSION
CAN is the impairment of cardiovascular autonomic control in the setting of diabetes after exclusion of other causes.
Ewing et al (5) recommend ve simple tests, the cardiac autonomic reex tests, to establish the diagnosis: 1) HRV with deep
breathing; 2) HRV lying to standing; 3) the Valsalva maneuver; 4) postural fall in blood pressure; and 5) blood pressure
response to sustained handgrip. A single abnormal test may
indicate early CAN, and three positive tests are recommended
for a denite diagnosis (3).
In early subclinical CAN, the cardiovascular autonomic reex tests may not be able to detect any abnormalities; however,
CAN is also detected by abnormal plasma catecholamine and
cardiac imaging (1, 6, 7). Scintigraphy has been vital in diagnosing subclinical CAN (3). Diastolic dysfunction is observed
with the echocardiogram, while cardiac magnetic resonance
imaging can detect early stages of CAN via myocardial torsion
(8). Pappachan et al found a connection between CAN and
prolongation of QTc and suggested that QTc can be used to
diagnose CAN (9). However, Valensi et al found that QTc was
not signicantly dierent between diabetic patients with and
without CAN and control patients (10).
The progression of CAN usually begins with parasympathetic denervation, followed by sympathetic tone enhancement
From the Division of Cardiovascular Medicine, Northside Hospital, Atlanta, Georgia.

Corresponding author: Barry Silverman, MD, Northside Heart, 5670 PeachtreeDunwoody Road, Atlanta, GA 30342 (e-mail: mssbds@gmail.com)
157
and eventually sympathetic denervation (1, 11, 12); therefore,

resting tachycardia is often the presenting sign (ranging from
100 to 130 bpm). As CAN progresses in severity, there is a
decrease in heart rate. Patients with subclinical CAN will have
abnormalities in HRV, which is followed by changes in baroreex sensitivity (3, 13). With advanced CAN, sympathetic
denervation along with impaired baroreex sensitivity and decreased norepinephrine response to change in posture will result
in orthostasis (3).
The pathological mechanism of CAN remains uncertain
but is likely multifactorial (14). What seems to be fundamental
in the development and progression of CAN is hyperglycemia
and its activation of multiple metabolic and/or redox pathways.
This, in conjunction with reduced blood ow to nerve bers,
contributes to the disorder (1). Myocardial blood ow activity
in response to sympathetic stimulation is signicantly impaired
after longstanding type 1 DM and may contribute to the eventual development of myocardial injury (15).
CAN prevalence increases with age and a longer duration
of diabetes. However, in select patients, it occurs in youth
early in the course of the disease (15). CAN is linked to mortality risk, as shown by a metaanalysis of 15 dierent studies
(16). In the EURODIAB Prospective Complications Study,
albuminuria and peripheral and autonomic neuropathy had
a strong association with mortality in patients with type 1
DM (17).
There are limited therapeutic approaches to prevent or reverse CAN, and this may be due to the fact that the exact
mechanisms behind the development of CAN are not understood. Lifestyle modications have improved moderate CAN
(1). Weight loss in obese diabetics and aerobic exercise for patients with both type 1 and type 2 DM improved HRV and
cardiac autonomic functionality (1, 3). Early and comprehensive
glycemic control is thought to prevent diabetic complications
and potentially reverse CAN symptoms (1, 3).
One therapy that may be eective in the management of
CAN is the beta-blocker bisoprolol, which was shown to increase HRV related to parasympathetic activity in heart failure
(18). Gottlieb et al noted that postmyocardial infarction diabetic patients had a 36% reduction in mortality with the use of
beta-blockers (19). The use of angiotensin-converting enzyme
inhibitors hinders downstream sympathetic outow; 1-year use
of quinapril resulted in some benet for treating CAN (20),
while a year of trandolapril resulted in no benets of autonomic
function or neuropathy symptoms in patients with CAN (21).
Diabetic patients with neuropathy were treated for a year with
an aldose reductase inhibitor (zopolrestat) and showed improved
resting and exercise left ventricular ejection fractions, cardiac
output, and stroke volume (22).
Orthostasis can be treated both pharmacologically and with
lifestyle changes. Midodrine and 9-alpha-ourohydrocortisone
improved systolic blood pressure upon standing (23, 24). Somatostatin and somatostatin analogues (octreotide) increased
blood pressure in patients with autonomic neuropathy (25).
Pyridostigmine bromide improved symptoms without worsening supine hypertension (26).
158
CAN is underrecognized in diabetic patients. Autonomic

testing is a helpful and cost-eective aid to diagnosis. CAN is
a common disorder that is not only associated with DM but
also occurs in patients with malignancy, autoimmune disorders,
Parkinsons disease, and a number of other neurologic and
medical disorders. It is important to identify these patients to
understand their signs and symptoms and consider appropriate therapies.
1.
2.
3.
4.
5.
6.
7.
8.
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10.
11.
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19.
Pop-Busui R. What do we know and we do not know about cardiovascular

autonomic neuropathy in diabetes? J Cardiovasc Transl Res 2012;5:463
468.
Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003;26(5):1553-1579.
Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014;5(1):1739.
Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui
R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment,
diagnosis, and management. Diabetes Metab Res Rev 2011;27(7):639653.
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular
autonomic function tests: 10 years experience in diabetes. Diabetes Care
1985;8(5):491498.
Bernardi L, Spallone V, Stevens M, Hilsted J, Frontoni S, Pop-Busui R.
Methods of investigation for cardiac autonomic dysfunction in human
research studies. Diabetes Metab Res Rev 2011;27(7):654664.
Stevens MJ. New imaging techniques for cardiovascular autonomic neuropathy: a window on the heart. Diabetes Technol Ther 2001;3(1):922.
Vanninen E, Mustonen J, Vainio P, Lnsimies E, Uusitupa M. Left ventricular function and dimensions in newly diagnosed non-insulin-dependent
diabetes mellitus. Am J Cardiol 1992;70(3):371378.
Pappachan JM, Sebastian J, Bino BC, Jayaprakash K, Vijayakumar K,
Sujathan P, Adinegara LA. Cardiac autonomic neuropathy in diabetes
mellitus: prevalence, risk factors and utility of corrected QT interval in
the ECG for its diagnosis. Postgrad Med J 2008;84(990):205210.
Valensi PE, Johnson NB, Maison-Blanche P, Extramania F, Motte G,
Coumel P. Inuence of cardiac autonomic neuropathy on heart rate dependence of ventricular repolarization in diabetic patients. Diabetes Care
2002;25(5):918923.
Schnauer M, Thomas A, Morbach S, Niebauer J, Schnauer U, Thiele H.
Cardiac autonomic diabetic neuropathy. Diab Vasc Dis Res 2008;5(4):336
344.
Jordan J, Tank J. Complexity of impaired parasympathetic heart rate
regulation in diabetes. Diabetes 2014;63(6):18471849.
Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007;115(3):387397.
Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy:
mechanisms to management. Pharmacol Ther 2008;120(1):134.
Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1
diabetes and cardiovascular disease. Cardiovasc Diabetol 2013;12(1):156
166.
Maser RE, Mitchell BD, Vinik AI, Freeman R. The association between
cardiovascular autonomic neuropathy and mortality in individuals with
diabetes: a meta-analysis. Diabetes Care 2003;26(6):18951901.
Soedamah-Muthu SS, Chaturvedi N, Witte DR, Stevens LK, Porta M,
Fuller JH. EURODIAB Prospective Complications Study Group. Relationship between risk factors and mortality in type 1 diabetic patients
in Europe: the EURODIAB Prospective Complications Study (PCS).
Diabetes Care 2008;31(7):13601366.
Pousset F, Copie X, Lechat P, Jaillon P, Boissel JP, Hetzel M, Fillette F,
Remme W, Guize L, Le Heuzey JY. Eects of bisoprolol on heart rate
variability in heart failure. Am J Cardiol 1996;77(8):612617.
Gottlieb SS, McCarter RJ, Vogel RA. Eect of beta-blockade on mortality
among high-risk and low-risk patients after myocardial infarction. N Engl
J Med 1998;339(8):489497.
Volume 29, Number 2
20. Athyros VG, Didangelos TP, Karamitsos DT, Papageorgiou AA,

Boudoulas H, Kontopoulos AG. Long-term eect of converting enzyme inhibition on circadian sympathetic and parasympathetic modulation in patients with diabetic autonomic neuropathy. Acta Cardiol
1998;53(4):201209.
21. Malik RA, Williamson S, Abbott C, Carrington AL, Iqbal J, Schady W,
Boulton AJ. Eect of angiotensin-converting-enzyme (ACE) inhibitor
trandolapril on human diabetic neuropathy: randomised double-blind
controlled trial. Lancet 1998;352(9145):19781981.
22. Johnson B, Nesto R, Pfeifer MA, Slater WR, Vinic AI, Chyun DA, Law
G, Wackers F, Young L. Cardiac abnormalities in diabetic patients with
neuropathy: eects of aldose reductase inhibitor administration. Diabetes
Care 2004;27(2):448454.
April 2016
23. Jankovic J, Gilden JL, Hiner BC, Kaufmann H, Brown DC, Coghlan CH,
Rubin M, Fouad-Tarazi FM. Neurogenic orthostatic hypotension: a doubleblind, placebo-controlled study with midodrine. Am J Med 1993;95(1):3848.
24. Campbell IW, Ewing DJ, Clarke BF. 9-Alpha-uorohydrocortisone in
the treatment of postural hypotension in diabetic autonomic neuropathy.
Diabetes 1975;24(4):381384.
25. Hoeldtke RD, Bryner KD, Hoeldtke ME, Hobbs G. Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with
octreotide LAR. Clin Auton Res 2007;17(6):334340.
26. Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM,
Hines S, OBrien PC, Slezak J, Low PA. Pyridostigmine treatment trial
in neurogenic orthostatic hypotension. Arch Neurol 2006;63(4):513
518.
Cardiovascular autonomic neuropathy
159
Cardiac arrest refractory to standard intervention in atypical

Timothy syndrome (LQT8 type 2)
Lucas R. Philipp, BA, and Fred H. Rodriguez III, MD
Timothy syndrome (TS) is a rare, multisystem disorder most commonly

associated with profound QTc prolongation and cutaneous dysmorphia
arising from mutations of the L-type calcium channel. We present a case
of a 12-day-old newborn who presented with respiratory distress and
cyanosis. Diagnostic workup was notable for multiple cardiac abnormalities, and genetic analysis was consistent with an exon 8 mutation
of the CACNA1C gene, which is diagnostic for TS type 2 (atypical TS).
This patient presented with a novel constellation of symptoms, without
dysmorphic features, and with a more moderate QTc interval. The heterogeneity of phenotypes suggests that this disorder may be characterized
by variable expressivity or a spectrum of disease rather than a clearly
defined syndrome.
imothy syndrome (TS) is a rare, multisystem disorder

associated with profound QTc prolongation and syndactyly, formally described by Splawski and Timothy
et al (13). Also known as long-QT syndrome type 8
(LQTS8), TS is caused by gain of function mutations aecting
the L-type calcium channel CACNA1C gene. Additional syndromic features include facial dysmorphia, cardiac anomalies,
and cognitive impairment (13). TS has been described in less
than 50 patients, 5 of whom were noted to have phenotypic/
genotypic variations known as atypical TS (46). These patients
lack syndactyly and have demonstrated a greater frequency and
severity of cardiac symptoms (5). The paucity of atypical TS
cases denotes clear limitations in our ability to produce generalizable conclusions with respect to genotype-phenotype interactions. We describe the youngest documented case of atypical
TS in a 12-day-old infant with clinical ndings unique from
prior cases.
CASE REPORT
Within the patients rst 5 days of life, she experienced
intermittent hypoglycemia and hypocalcemia, an episode of
bradycardia, desaturation, and abnormal ndings on electrocardiography (Figure 1). The echocardiogram showed a patent
ductus arteriosus with normal left ventricular systolic function.
The infant developed severe shortness of breath and episodic
fainting spells at 12 days postdelivery. Arterial blood gas showed
a pH of 6.9 with lactic acidosis (20.16 mmol/L). Calcium and
160
bicarbonate were given. The patients chest x-ray, lumbar puncture, and all cultures were unremarkable. The electrocardiogram
showed 2:1 AV conduction (ventricular rate 69 bpm) and a
QTc of 636 ms (Figure 1). The brain natriuretic peptide level
was 21,000 pg/mL. An echocardiogram showed biventricular
systolic dysfunction (Figure 2). Milrinone and esmolol drips
were initiated. The patient underwent patent ductus arteriosus ligation, and temporary A/V pacing wires were placed. A
dual-chamber permanent pacemaker was later implanted via a
subxiphoid approach with epicardial right atrial and left ventricular leads. The initial mode was DDD 80-210 (activation
rateupper limit of detection), but was revised to DDD 90-210.
The results of the GeneDX long QT gene panel were positive
for a heterozygous mutation of the CACNA1C gene, demonstrating the Gly406Arg (G406R) mutationa c.1216 G>A in
exon 8. This patient had no syndactyly or facial dysmorphia.
Her family history was negative for congenital and genetic defects. The patient was discharged on day 25 in good condition.
The child returned with cardiac arrest with metabolic acidosis (pH 6.78, lactic acid 11.26) 2.5 weeks later. She developed ventricular brillation, was debrillated to resume sinus
rhythm, and received magnesium and calcium. She was then
bolused with lidocaine and started on a lidocaine drip. Ventricular ectopy and intermittent ventricular tachycardia persisted.
Esmolol was started. She had signicant hypotension (systolic
pressure 3050 mm Hg) requiring vasopressor support. A repeat
echocardiogram showed persistence of her severely depressed
biventricular systolic function, and milrinone was added. She
continued to have neurologic problems, and a computed tomography scan showed extensive hypoxic ischemic brain injury.
After discussion with her parents, care was withdrawn, and the
infant died on her 52nd day of life.
DISCUSSION
TS type 1 accounts for most TS cases and is associated with
a 100% incidence of cutaneous syndactyly (2). Severe cardiac
From Emory University School of Medicine (Philipp, Rodriguez) and Sibley Heart
Center Cardiology (Rodriguez), Atlanta, Georgia.
Corresponding author: Lucas R. Philipp, 12180 S. Solomon Road, Olathe, KS
66061 (e-mail: Lrphili@emory.edu).
Figure 1. Characteristic electrocardiographic findings in this patient from lead II tracings at various times during hospitalization: (a) the most frequent finding in
this patient, showing 2:1 AV block (ventricular rate = 69 bpm; atrial rate = 138 bpm) and a prolonged QTc (622 ms); (b) 1:1 AV conduction (heart rate = 119
bpm), QTc = 558 ms, with T-wave alternans; (c) QTc = 659 ms with 2:1 AV conduction (ventricular rate = 82 bpm; atrial rate = 164 bpm).
symptoms underlie nearly every diagnosis of TS, including

repolarization abnormalities such as a QTc of 480 to 700 ms,
2:1 AV block, and T wave alternans. Structural defects are also
common (4). The leading cause of death is ventricular tachyarrhythmia, which is present in 80% of individuals.
TS type 1 is an autosomal dominant condition, arising from
de novo mutations in exon 8a of CACNA1C, which codes for
the CaV1.2 protein (4, 7). This results in a Gly406Arg substitution that alters calcium channel inactivation, leading to
excess calcium inux and action potential prolongation. Rare
cases have described inheritance patterns of somatic mosaicism,
which is associated with a milder phenotype (2, 5, 8). The

G406R mutation in the CACNA1C gene has also been associated with atypical TS (2, 9, 10). However, atypical TS (TS
types 2 and 3) arises from mutations in exon 8 of CACNA1C.
Exon 8 is mutually exclusive with exon 8a, exon 8 mRNA being
the predominant isoform in most tissues (7). In the context of
this current understanding of the disorder, the present patient
was genotype positive for atypical TS; however, her phenotype
was unique. Although a greater incidence and severity of facial
dysmorphia has been noted in atypical TS (2), this infant had
normal facial features.
Figure 2. Key echocardiogram findings on the first hospital readmission after birth. (a) Apical four-chamber view illustrating left ventricular noncompaction and
biventricular hypertrophy. (b) Parasternal long-axis image showing left ventricular hypertrophy and left ventricular noncompaction. (c) M-mode image showing
moderately to severely depressed left ventricular systolic function. Fractional shortening 17.9%.
April 2016
Cardiac arrest refractory to standard intervention in atypical Timothy syndrome (LQT8 type 2)
161
Previous studies have suggested that CACNA1C exon 8 TS

genotypes are associated with a more extreme prolongation of
QTc in aected individuals, ranging between 620 and 730 ms
(4, 5, 9). A proposed explanation is the predominance of exon
8 mRNA products in the heart (80%) relative to those of 8a
(5). The QTc of our patient ranged from 487 to 660 ms, with
a mean of approximately 550 ms. This range falls short of the
originally described features of atypical TS (2), but exceeds the
normal rate-corrected ranges by a large margin.
Since our patient was diagnosed at such a young age, we
were initially optimistic about her prognosis. We had hoped that
with early medical intervention, we would have been able to effectively treat potentially lethal heart rhythms in a prophylactic
manner. However, although we successfully placed a cardiac
pacemaker in this patient, its function does not address the
underlying abnormal cellular pathology within the cardiomyocytes of atypical TS patients. It is of substantial importance to
consider the sharp juxtaposition the present case poses to prior
reports (11). Our patient received standard, evidence-based
treatment at an exceptionally early time in the course of her
disease. In spite of this, these interventions were not successful.
This patient presented with a novel constellation of symptoms, including a more moderate QTc interval and a lack of the
facial dysmorphia that has accompanied all prior cases of atypical
TS. The heterogeneity of phenotypes observed in atypical TS
may suggest that the disorder is characterized by variable expressivity or is a spectrum of disease rather than a clearly dened
syndrome. Most importantly, it has been previously suggested
that early medical intervention may be pivotal in preventing early
cardiac fatalities in atypical TS. However, pacemaker implantation did not prevent ventricular dysrhythmias in our patient. The
extent to which this channelopathy disrupts normal electrical
activity of the heart may have been previously underestimated,
and other potential therapies need to be explored.
162
1. Reichenbach H, Meister EM, Theile H. The heart-hand syndrome. A

new variant of disorders of heart conduction and syndactylia including
osseous changes in hands and feet. Kinderarztl Prax 1992;60(2):54
56.
2. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R,
Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg
H, Priori SG, Sanguinetti MC, Keating MT. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and
autism. Cell 2004;119(1):1931.
3. Marks ML, Whisler SL, Clericuzio C, Keating M. A new form of long QT
syndrome associated with syndactyly. J Am Coll Cardiol 1995;25(1):59
64.
4. Yazawa M, Dolmetsch RE. Modeling Timothy syndrome with iPS cells.
J Cardiovasc Transl Res 2013;6(1):19.
5. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH,
Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by
cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA
2005;102(23):80898096.
6. Hiippala A, Tallila J, Myllykangas S, Koskenvuo JW, Alastalo T-P. Expanding the phenotype of Timothy syndrome type 2: an adolescent
with ventricular brillation but normal development. Am J Med Genet A
2015;167A(3):629634.
7. Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL. Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium
channel transcript by polypyrimidine tract-binding protein. J Biol Chem
2011;286(12):1000710016.
8. Etheridge SP, Bowles NE, Arrington CB, Pilcher T, Rope A, Wilde AA,
Alders M, Saarel EV, Tavernier R, Timothy KW, Tristani-Firouzi M.
Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. Am J Med Genet A 2011;155A(10):25782583.
9. Yarotskyy V, Gao G, Peterson BZ, Elmslie KS. The Timothy syndrome
mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating
mechanisms and pharmacological restoration of inactivation. J Physiol
2009;587(Pt 3):551565.
10. Dufendach KA, Giudicessi JR, Boczek NJ, Ackerman MJ. Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome.
Pediatrics 2013;131(6):e1991e1995.
11. Diep V, Seaver LH. Long QT syndrome with craniofacial, digital, and
neurologic features: is it useful to distinguish between Timothy syndrome
types 1 and 2? Am J Med Genet A 2015;167(11):27802785.
Volume 29, Number 2
Holter monitor recordings in a man who snores

D. Luke Glancy, MD, and Prasert Vijitbenjaronk, MD
lectrocardiographic
a
rhythm strips were
recorded over a
24-hour period in
a 49-year-old man who
snored but had no prior
b
cardiac history and no
rhythm disturbances
while awake. A modied
lead II strip recorded at
4:06 am showed marked
sinus arrhythmia and
c
second-degree AV block
(Figure 1a). The AV block
increased when the sinus
rate slowed, suggesting
increased vagal tone affecting both the sinus and
the AV nodes. The fourth
QRS was slightly wider
than the others and may
have been junctional escape complex; its T wave
was considerably wider Figure 1. Electrocardiograms over a 24-hour period. Modified lead II strips showing (a) marked sinus arrhythmia and secondthan the others and prob- degree AV block at 4:06 AM and (b) normal sinus rhythm at 4:09 AM. (c) Continuous modified V1 rhythm strips recorded at
ably contained a sinus P 11:52 PM showing marked slowing of the sinus rate accompanied by sudden high-grade AV block.
wave. A modied lead II
strip recorded 3 minutes later showed normal sinus rhythm
occur predominantly or, as in this patient, exclusively during
throughout (Figure 1b). Modied V1 rhythm strips recorded
sleep. Relief of the upper airway obstruction has reduced the
at 11:52 pm showed marked slowing of the sinus rate accompafrequency and severity of rhythm disturbances (1). Continunied by sudden high-grade AV block with ventricular asystole
ous positive airway pressure (CPAP) reduces the arrhythmia
of 5.46 seconds that was terminated by a ventricular escape
recurrence rate following pulmonary vein isolation for atrial
complex (with a sinus P wave in its ST segment). Afterwards,
brillation in patients with obstructive sleep apnea and inthere was a slight increase in the sinus rate accompanied by
creases atrial brillation-free survival o antiarrhythmic drugs
marked rst-degree AV block. Again, sudden, transient highor repeat ablation. Pulmonary vein isolation appears to oer
grade AV block accompanying slowing of the sinus rate suglimited value to patients with obstructive sleep apnea not
gested increased vagal tone (Figure 1c).
treated with CPAP (5).
In addition to its association with bradyarrhythmias,
obstructive sleep apnea has been associated with ventricular
From the Sections of Cardiology, Louisiana State University Health Sciences
ectopy, including nonsustained ventricular tachycardia, atrial
Center and the Touro Infirmary, New Orleans, Louisiana.
brillation, and atrial utter (13). Obstructive sleep apnea is
Corresponding author: D. Luke Glancy, MD, 1203 West Cherry Hill Loop, Folsom,
also associated with sudden cardiac death (4). The arrhythmias
LA 70437 (e-mail: dglanc@lsuhsc.edu).
163
1.
2.
3.
Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and

conduction disturbances during sleep in 400 patients with sleep apnea
syndrome. Am J Cardiol 1983;52(5):490494.
Javaheri S, Parker TJ, Liming JD, Corbett WS, Nishiyama H, Wexler L,
Roselle GA. Sleep apnea in 81 ambulatory male patients with stable heart
failure. Types and their prevalences, consequences, and presentations.
Circulation 1998;97(21):21542159.
Mehra R, Stone KL, Varosy PD, Homan AR, Marcus GM, Blackwell T,
Ibrahim OA, Salem R, Redline S. Nocturnal arrhythmias across a spectrum
4.
5.
of obstructive and central sleep-disordered breathing in older men: outcomes of sleep disorders in older men (MrOS sleep) study. Arch Intern
Med 2009;169(12):11471155.
Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden
death in obstructive sleep apnea. N Engl J Med 2005;352(12):12061214.
Fein AS, Shvilkin A, Shah D, Haajee CI, Das S, Kumar K, Kramer
DB, Zimetbaum PJ, Buxton AE, Josephson ME, Anter E. Treatment of
obstructive sleep apnea reduces the risk of atrial brillation recurrence
after catheter ablation. J Am Coll Cardiol 2013;62(4):300305.
In memoriam
CHARLES DALE COLN, MD
Author: Department of Pediatric Surgery, Baylor University
Medical Center at Dallas
Dr. Dale Coln, who served as the rst chief of pediatric
surgery at Baylor University Medical Center (BUMC), died
January 5, 2016, from complications of Alzheimers disease.
He was 81 years old. Dr. Coln grew up in Dallas, attending
Arlington Heights High School. He received his bachelors
degree from Baylor University, followed by a medical degree
from Baylor University College of Medicine in 1961. After
medical school, he married Dr. Shirley Kindberg, a pediatrician who later directed BUMCs newborn nursery. Dr. Coln
completed a research fellowship with Dr. G. Tom Shires in
Dallas and a surgery residency at Parkland Hospital. He was
in the Parkland emergency room when Lee Harvey Oswald
was brought in 2 days after Kennedys assassination. Several
years after beginning his surgical practice, Dr. Coln completed
a fellowship in pediatric surgery in Cape Town, South Africa,
and in 1972, he was named chairman of pediatric surgery at
Parkland. One of his legacies there was establishing a pediatric
trauma unit. He became chairman at BUMC in 1987. For
decades, until his retirement in 2005, he treated children both
in Dallas and in his nine mission trips to Guatamela. He was
especially known for the Nuss procedure, used for correcting
congenital chest wall abnormalities. Recognized throughout
his career for his compassionate care of children, Dr. Colns
many honors include the American Academy of Pediatrics
164
Special Achievement Award in 2001 and the Childrens Medical Centers Distinguished Service Award in 2002. Tributes to
Dr. Coln were published on his retirement and are available at
http://www.baylorhealth.edu/Documents/BUMC%20Proceedings/2005%20Vol%2018/No.%204/18_4_tributes_coln.pdf.
GLENN WELDON TILLERY, MD

Department of Pathology, Baylor University Medical Center
Dr. Glenn Weldon Tillery was born on December 29, 1932,
and died on January 13, 2016, at the age of 83. Born in Lubbock, Texas, Dr. Tillery attended Lubbock High School, the
University of New Mexico, and the University of Texas Southwestern Medical School. During medical school, he married
Mary Swan, who was working as a laboratory technician at
Baylor Hospital. He competed an internship in internal medicine at the Dallas VA Hospital from 1959 to 1960 and served
as a ight surgeon in the US Air Force in San Antonio. Dr.
Tillery then pursued a pathology residency at BUMC under
the direction of Dr. George Race. Early in his pathology career,
he was recruited by Arabian American Oil Co. and served as
chief of pathology services in Dhahran, Saudi Arabia. He then
returned to BUMCs pathology department and was chief of the
department from 1986 to 1999. His inuence at the medical
center through the years was considerable, and he was a major
force in building the Department of Pathology at BUMC. He
retired in 2012.
Volume 29, Number 2
An interesting electrocardiogram
Howard H. McClure Jr., MD
aving spent years

collecting electrocardiograms (ECGs), I
found this one the
most intriguing (Figure). Try
to solve it. Two hints: (1) dont
be seduced by the top row; and
(2) a caliper is useful.
SOLUTION
At first blush, the strip
across the top appears to be
2:1 block. On more careful
inspection, it appears the PR
is shortening, suggesting the
possibility of an ectopic pacer.
If one takes that cycle length
(RR interval), it can be identied elsewhere in the record.
This is a junctional escape Figure. An interesting electrocardiogram.
pacemaker; all the other beats
are sinus capture with a variety of PR intervals. These intervals
the atrioventricular node and not conduct. Every component
are determined by the preceding RP (i.e., recovery time of the
of the record has a rational explanation.
atrioventricular node; Henry Marriotts famous RP-dependent
One of the confusing features of this tracing is that coPR). The last two beats in the third strip have the longest and
incidentally, the sinus rate of 76 is almost a multiple of the
shortest PRs. They also have the shortest and longest RPs. If the
independent junctional rate of 39. This may lead to confusion
RP is too short, it may fall in the absolute refractory period of
that a P and a QR are related when they are not!
From Baylor University Medical Center at Dallas.

Corresponding author: Howard H. McClure Jr., MD, 1519 Marseille Place,
Dallas, TX 75204 (e-mail: hhmcmd@gmail.com).
165
Takotsubo cardiomyopathy after administration of

norepinephrine
Khaled Sherif, MD, Sharmila Sehli, MD, and Leigh A. Jenkins, MD
Stress-induced cardiomyopathy is a syndrome

of transient cardiac dysfunction with no clear
pathophysiology. It is
thought to be secondary to catecholamine
surge. The mechanism
by which catecholamine
can induce transient
cardiac dysfunction is
unknown. We present
a case of a patient
who developed stressinduced cardiomyopathy
after she was administered norepinephrine
due to a nursing error.
tress-induced Figure 1. ECG showing ST segment and T wave changes.

cardiomyopathy (also known as takotsubo cardiomyopathy, TC) is
of packed red blood cells with furosemide were ordered. After the
a syndrome of transient cardiac dysfunction precipitated
patient received blood, norepinephrine (Levophed) 4 mg intraveby intense emotional or physical stress. It has been recognized
nously was given instead of furosemide 40 mg due to a nursing
in Japan since 1991 (1). The prevalence of TC in the general
error. Soon after that, the patient started complaining of chest pain
population is estimated to be between 1.7% and 2.2% in pawith dyspnea and was in acute distress with tachypnea and expiratients who present with suspected acute coronary syndrome. It is
tory wheezing. An electrocardiogram showed new ST segment
characterized by acute chest pain, electrocardiographic changes,
and T wave changes in the precordial leads (Figure 1). Her tropoand elevated cardiac biomarkers in the absence of obstructive
nin T level was 0.44 ng/mL; creatinine kinase, 131 ng/mL; and
coronary artery disease. It can be classied into a left ventricucreatinine kinasemyocardial band, 6.9 ng/mL. A transthoracic
lar apical ballooning variant (most common), an inverted or
echocardiogram showed severely depressed left ventricular systolic
reverse variant (basal akinesis with hyperdynamic apex), and
function with an ejection fraction of 25% to 29% with apical wall
a midventricular variant. We present a patient who developed
akinesis and hypokinesis of anterior, anteroseptal, and anterolateral
TC after receiving a norepinephrine injection.
CASE REPORT
A 76-year-old woman with hypertension, type 2 diabetes mellitus, and diverticulosis presented with bright red rectal bleeding.
On admission, she was hemodynamically stable. She was found to
have normocytic anemia with a hemoglobin of 7.8 g/dL. Two units
166
From the Department of Internal Medicine, Texas Tech University Health Sciences
Center, Lubbock, Texas.
Corresponding author: Khaled A. Sherif, MD, Department of Internal Medicine,
Texas Tech University Health Sciences Center, 3601 4th Street, MS 9410,
Lubbock, TX 79430 (e-mail: k_a_sherif@hotmail.com).
Figure 2. Left ventriculogram showing apical ballooning.
walls. Coronary angiography showed no evidence of signicant

obstructive coronary artery disease. A left ventriculogram showed
mildly depressed left ventricular systolic function and an ejection
fraction of 45%, with evidence of apical ballooning (Figure 2).
The diagnosis of takotsubo cardiomyopathy was made. The
patient was treated with beta-blockers, angiotensin-converting
enzyme inhibitors, and aldosterone antagonist for heart failure
symptoms. She improved over time and was discharged home. A
transthoracic echocardiogram after 6 months showed an ejection
fraction of 50% to 55%.
DISCUSSION
The left ventricular dysfunction that occurs with stressinduced cardiomyopathy is thought to be secondary to catecholamine surge brought on by intense psychological or physical
stress. Much of the evidence for this comes from observational
and case-control studies that have found an association between
elevated catecholamine levels and disease onset. The mechanism
by which catecholamine can induce transient left ventricular dysfunction is unclear. It is possible that high doses of catecholamine
are directly toxic to myocardial cells. This is supported by histological ndings from animal studies and autopsy ndings from
TC patients that document myobril degeneration, contraction
band necrosis, and leukocyte inltration (2). Molecular studies in
cultured cardiocytes have shown that high doses of epinephrine
April 2016
are directly toxic to the cells. This results in a signicant rise in

cyclic adenosine monophosphate and calcium levels that trigger
the formation of free oxygen radicals, initiation of expression of
stress response genes, and induction of apoptosis in a subset of
cells (3, 4). Myocardial necrosis cannot explain the entire picture because most patients with TC regain full recovery of left
ventricular function. It has been proposed that epinephrine may
cause damage by inducing spasm of coronary macro- and microvasculature and/or stunning of cardiocytes directly because of
cyclic adenosine monophosphatemediated calcium overload (5).
About 80% of TC cases occur in postmenopausal women.
Studies have shown that estrogen plays an important role in
protecting the myocardium (6), possibly by downregulating
beta-adrenergic receptors. Postmenopausal women lose this
protection and are more vulnerable to the catecholamine surge
that is associated with stress. There is a predominance of the
apical ballooning variant. It was previously suggested that the
apex of the heart is more sensitive to epinephrine due to a
higher density of beta-adrenergic receptors in the cardiac apex
versus the base (4).
In our case, the patient accidentally received a high dose of
norepinephrine, which stimulates alpha and beta-1 adrenergic
receptors and produces both positive ionotropic and vasodepressor eects. The patient developed the classic form of TC, and
this case conrms the direct causal role of catecholamine in the
pathophysiology of TC. In the past, several cases of iatrogenically induced TC have been reported. To the best of our knowledge, this is the rst report of stress-induced cardiomyopathy
secondary to iatrogenic norepinephrine injection.
1.
2.
3.
4.
5.
6.
Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. [Myocardial stunning

due to simultaneous multivessel coronary spasms: a review of 5 cases].
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Movahed A, Reeves WC, Mehta PM, Gilliland MG, Mozingo SL, Jolly
SR. Norepinephrine-induced left ventricular dysfunction in anesthetized
and conscious, sedated dogs. Int J Cardiol 1994;45(1):2333.
Mann DL, Kent RL, Parsons B, Cooper G IV. Adrenergic eects on the
biology of the adult mammalian cardiocyte. Circulation 1992;85(2):790
804.
Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (takotsubo) cardiomyopathya novel pathophysiological hypothesis to explain
catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc
Med 2008;5(1):2229.
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP,
Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress.
N Engl J Med 2005;352(6):539548.
Ueyama T, Hano T, Kasamatsu K, Yamamoto K, Tsuruo Y, Nishio I.
Estrogen attenuates the emotional stress-induced cardiac responses in
the animal model of tako-tsubo (ampulla) cardiomyopathy. J Cardiovasc
Pharmacol 2003;42(Suppl 1):S117S119.
Takotsubo cardiomyopathy after administration of norepinephrine
167
Acute myocardial infarction with isolated congenitally

corrected transposition of the great arteries
Jeremy Zimmermann, DO, J. Ryan Altman, MD, and D. Scott Gantt, DO
Congenital cardiac abnormalities diagnosed at the time of acute coronary

syndrome are rare. A 43-year-old man presented to the emergency
department complaining of recurring, severe chest pain. Subsequent
emergent coronary angiography demonstrated unusual coronary anatomy: 1) one small caliber bifurcating vessel originating from the right
sinus of Valsalva; 2) one very large vessel arising from the posterior
sinus; and 3) no coronary artery from the normal left sinus of Valsalva.
The large vessel from the posterior sinus was totally occluded in its
midportion and was treated with intravascular ultrasound-guided percutaneous coronary intervention. Further diagnostic workup, including twodimensional transthoracic echocardiogram and computed tomographic
coronary angiography, demonstrated isolated corrected transposition of
the great arteries with a dilated systemic ventricle and systolic dysfunction with an ejection fraction of 30%. The patients clinical course was
complicated by recurrent nonsustained ventricular tachycardia, treated
with medical therapy and a dual-chamber implantable cardioverter
defibrillator. This case is an example of a common clinical presentation
with a very uncommon congenital heart disorder. Similar cases may
become more frequent as the number of adult congenital heart patients
increases in the population.
e novo diagnosis of congenital cardiac abnormalities is uncommon in the average adult cardiology
practice. Th ese patients can present a signi cant
diagnostic challenge when they develop acute coronary syndrome. Described below is an example of a common
clinical presentation with a very uncommon congenital heart
disorder.
CASE REPORT
A 43-year-old white man presented to the emergency department complaining of chest pain. He was known to have
hypertension, tobacco abuse, antisocial personality disorder, and
chronic obstructive pulmonary disease. His chest pain began
the night prior to presentation while watching television and
lasted several hours. The pain was substernal, with radiation to
his back, and was alleviated by lying prone, allowing the patient
to sleep through the night. The following day, he developed
recurrent pain and after 2 hours was convinced by his girlfriend
168
to seek medical attention. The patient had maintained a normal

active lifestyle throughout childhood into his fourth decade of
life, developing mild dyspnea with exertion over the 6 months
prior to his presentation.
His initial electrocardiogram (ECG) demonstrated sinus
tachycardia, left axis deviation, nonspecic intraventricular conduction delay, left atrial enlargement, and old anteroseptal infarct,
without dextrocardia (Figure 1). A portable chest radiograph
demonstrated increased central vascular prominence with cephalization, mild cardiomegaly, and no dextroversion (Figure 2).
Emergent coronary angiography revealed a relatively small
caliber vessel arising from an anterior cusp, bifurcating into
small caliber branches without stenosis (Figure 3). A second
coronary artery was found originating from the posterior cusp
supplying much of the inferior lateral region. This vessel was
large caliber and was occluded in its midportion. Percutaneous
coronary intervention with a 5 16 mm Veriex bare-metal
stent was performed with subsequent intravascular ultrasound
demonstrating severe brocalcic plaque at the stenotic region
and good stent strut apposition. At the time of transfer to the
coronary care unit, the patient was free of chest pain and hemodynamically stable.
A transthoracic echocardiogram in the coronary care
unit demonstrated congenitally corrected transposition of
the great arteries (CTGA) with systemic ventricular dilatation and systolic dysfunction with an ejection fraction of
<30%. A computed tomographic angiogram of the coronary
arteries revealed a dominant coronary artery originating
from the posteriorly positioned right sinus of Valsalva with
a configuration most typical of a morphologic right coronary artery (Figure 3e, 3f ). The stent in the midportion of
the main branch was widely patent. The coronary artery
originating from the rightward rotated left cusp demonstrated a configuration most typical of a morphologic left
coronary artery.
From Baylor Scott & White Health and Texas A&M Health Science Center, Temple,
Texas.
Corresponding author: Jeremy Zimmermann, DO, Baylor Scott & White Health,
2401 S. 31st Street, Temple, TX 76508 (e-mail: jzimmermann@sw.org).
pulmonary artery and right

atrium, while the morphologic right ventricle and tricuspid valve are connected to the
left atrium and aorta, committing the right ventricle to
systemic pressure demands.
CTGA is rare and represents
<1% of congenital heart abnormalities (1). Up to 90% of
patients with CTGA have additional cardiac defects such
as ventricular septal defect,
pulmonary artery stenosis,
tricuspid valve abnormalities,
and mitral valve abnormalities (1). The clinical impact of
Figure 1. Initial presenting electrocardiogram showing sinus tachycardia, anterior Q waves, and a nonspecific ST segment these associated defects typically leads to diagnosis in the
elevation concerning for injury pattern.
rst few decades of life. In the
absence of these defects, termed isolated CTGA, the diagnosis
The patients clinical course was complicated by multiple
may be delayed into the fourth decade of life or later. These
episodes of symptomatic bradycardia with junctional rhythm
patients often present with worsening tricuspid regurgitation,
and several episodes of nonsustained ventricular tachycardia
systemic ventricular failure, and ventricular arrhythmias, cul>48 hours after his myocardial infarction. Along with iniminating in clinical congestive heart failure and the potential
tiation of medical therapy, a dual-chamber implantable carneed for cardiac transplantation (24). Ventricular arrhythdioverter debrillator was placed into the morphologic left
mias related to systolic heart failure and conduction system
ventricle, followed by discharge on hospital day 7. At followdisease with bradycardia and heart block are common. The
up 1 week later, the patient was asymptomatic with a benign
risk of developing complete heart block increases by 2% anexamination.
nually and is thought to be related to intrinsic conduction
system brosis (1).
DISCUSSION
In terms of the coronary artery anatomy, most patients
CTGA is associated with atrioventricular discordance and
with CTGA have coronary artery ventricular concordance,
ventriculoarterial discordance. The morphologic left ventricle
with the morphologic left ventricle supplied by a branching
and mitral valve are transposed to the right, attached to the
vessel similar to the left anterior descending and circumex
vessels, and the right ventricle supplied by a vessel similar to
a right coronary artery. Depending on the specic location
of the aorta and pulmonary artery, spatial orientation of the
coronary ostia can be challenging with standard angiography.
One case series from 1988 found that 11 out of 18 CTGA
patients had normal coronary artery ventricular concordance,
whereas the other 7 had signicant anomalies such as a single
coronary ostium or hypoplasia of the left anterior descending
artery (4).
This case is an example of a typical presentation of acute
coronary syndrome in a patient with a complex and rare congenital heart condition. During routine emergent coronary
angiography, the origin of the culprit vessel in the posterior sinus
of Valsalva was particularly challenging to engage. Advancing
modern medical therapy and surgical techniques inevitably will
result in a larger population of adult patients with congenital
heart conditions presenting for both routine preventive care
as well as emergency care. A thorough understanding of their
Figure 2. A portable chest radiograph obtained in the emergency department
pathology is becoming more important, as is the need for speshowing increased central vascular prominence with cephalization, mild cardiocialists in adult congenital heart disease.
megaly, and no dextroversion.
April 2016
Acute myocardial infarction with isolated congenitally corrected transposition of the great arteries
169
Figure 3. (a) Diagnostic invasive coronary angiography with a femoral approach demonstrates occlusion (arrow) of the large anomalous coronary branch that descends down the posterior aspect of the heart. (b) The distal portion of the occluded artery can be seen filling in after a wire was passed across the lesion. (c) The
patent vessel demonstrates good flow after deploying a bare-metal stent. (d) There was anomalous coronary circulation supplying the anterior wall of the pulmonary
ventricle. (e) Coronary CT angiogram demonstrates anterior displacement of the aortic root as well as the anomalous anterior coronary arteries. (f) Posterior view of
the coronary CT angiogram shows the large posterior descending branch and its large segment in the midportion where the stent was deployed (arrow).
1.
2.
170
Warnes CA. Transposition of the great arteries. Circulation 2006;

114(24):26992709.
Kaya A, Tanboga IH, Kurt M, Iik T, Ozgokce M, Topu S, Aksakal E.
Corrected transposition of the great arteries with previously unreported
cardiac anomalies. Cardiovasc J Afr 2012; 23(5):e5e7.
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4.
Kocabay G, Akturk S, Moe AS, Boztosun B. A rare coronary artery anomaly in a patient with isolated congenitally corrected transposition of great
arteries. J Am Geriatr Soc 2009;57(10):19401941.
Dabizzi RP, Barletta GA, Caprioli G, Baldrighi G, Baldrighi V. Coronary
artery anatomy in corrected transposition of the great arteries. J Am Coll
Cardiol 1988;12(2):486491.
Volume 29, Number 2
Isolated congenitally corrected transposition of the great

arteries with dextroversion discovered incidentally in a
patient with cocaine-induced acute myocardial infarction
Anumeha Tandon, MD, Rahul Bose, MD, Anthony D. Yoon, MD, and Jeffrey M. Schussler, MD
Complex cardiac congenital anomalies can occasionally be found in

adult patients who have no knowledge of their condition. Here we
present the case of a 27-year-old
man with cocaine-induced acute
myocardial infarction in whom an
isolated congenitally corrected
transposition of the great arteries
with dextroversion was discovered
incidentally.
hile congenital
anomalies are often left to subspecialists in the adult
congenital arena, familiarity
with them is important for Figure 1. Electrocardiogram demonstrating a reversal of the P-wave axis (inverted P waves in leads I, AVR, and AVF; arrow)
the general cardiologist. When with reversal of progression of R waves across the entire precordial leads (V1V6).
these patients present in association with other, more common conditions, evaluation can
anterior descending artery, but in a conformation that would be
be more challenging.
considered opposite of normal anatomy. The opposite coronary artery appeared similar in conformation to a right coronary
CASE DESCRIPTION
artery, but also had an opposite course (Figure 3).
A 27-year-old man presented with chest pain. A loud systolic
A transthoracic echocardiogram (with images obtained primurmur was heard at the right sternal border, and a rightward
marily from right-sided windows) revealed an aorta originating
displaced point of maximal impact was noted. The admission
from a morphologic right ventricle (systemic ventricle) and the
electrocardiogram showed prominent R waves in V1, with an
pulmonary trunk from a morphologic left ventricle (pulmonary
inverted P-wave axis, and reverse R wave progression across the
ventricle). These ndings were conrmed by cardiac computed
precordium (Figure 1). A chest radiograph demonstrated a righttomography (Figure 4). Abdominal ultrasound showed normally
ward-pointed heart, prominent right-sided chambers, and the
oriented viscera conrming situs solitus (normal orientation
absence of the usual aortic and pulmonary contours (Figure 2).
of the viscera). The patient was treated medically for cocaine
The urine was positive for cocaine. The patients troponin level
intoxication and was ultimately discharged in good condition.
was 55 ng/mL. At urgent cardiac catheterization, the ventriculogram in the left anterior oblique position disclosed the heart
From the Department of Internal Medicine, Division of Cardiology, Baylor University
pointing toward the right hemithorax, suggesting dextrocardia
Medical Center at Dallas (Tandon, Bose, Yoon, Schussler); the Jack and Jane
or dextroversion. Angiography showed no coronary narrowing,
Hamilton Heart and Vascular Hospital, Dallas, Texas (Tandon, Yoon, Schussler);
but demonstrated mirror image epicardial coronary arteries.
and Texas A&M College of Medicine (Schussler).
The most anterior coronary artery coursed toward the right side
Corresponding author: Jeffrey M. Schussler, MD, 621 N. Hall Street, Suite 400,
of the body and covered a distribution similar to that of a left
Dallas, TX 75226 (e-mail: Jeffrey.Schussler@Baylorhealth.edu).
171
Figure 2. Chest radiograph demonstrating a rightward-oriented heart, with the

morphologic left ventricle (LV) pointed towards the right. There is loss of the
normal aortopulmonary contours (arrowhead), and this area appears flat. The
gastric bubble is noted under the left hemidiaphragm, indicative of situs solitus
(normally oriented viscera).
DISCUSSION
Congenitally corrected transposition of the great arteries
(CCTGA) is a rare (<1% of all congenital heart disease) anomaly where the great arteries are transposed and the ventricles,
ventricular septum, atrioventricular valves, epicardial coronary
arteries, and the conduction system are inverted. Other congenital heart defects such as ventricular septal defect, pulmonary stenosis, anomalies of the systemic atrioventricular valve
(commonly, Ebsteins anomaly), and conduction defects are
present in approximately 98% of these patients. Most patients
are identied in childhood, usually due to complications from
the associated abnormalities. A minority of patients (particularly those without associated anomalies) may be asymptomatic
for many years and present later in life due to ndings on
physical or radiologic exams, or if they experience systemic
ventricular failure (1). Dextrocardia, or a rightward-pointing
heart, is seen in up to 20% of these patients, and CCTGA
should be strongly suspected when dextrocardia is observed
(2). Dextrocardia with situs solitus (normally oriented viscera)
and no other cardiac anomalies is rare, with an incidence of 1
live birth in 30,000 (3).
Figure 3. Systemic ventriculogram (morphologic right ventricle) with a rightward-oriented apex. (a) Standard left anterior oblique imaging demonstrates a systemic
ventricle that points towards the right side of the body. (b) Injection of the ascending aorta (Ao) fills the left main (LM) coronary artery. (c) Selective injection of the
LM fills arteries that are equivalent to the left anterior descending (LAD) and left circumflex (LCx) arteries, in that they supply blood to the anterior and lateral portions
of the systemic ventricle. (d) Injection of the posteriorly located coronary artery, equivalent to the right coronary artery (RCA), demonstrates that it supplies blood to
the posterior portions of the systemic ventricle.
172
Volume 29, Number 2
cardiac magnetic resonance

imaging, and invasive coronary angiography can all be
used in conjunction to allow
for accurate diagnosis.
Coronary anatomy, in
particular, is variable. In up
to 50% of patients, there
may be associated coronary
anomalies (4). Patients who
present with coronary atherosclerosis or acute coronary
syndromes are uncommon,
as these patients usually present with systemic ventricular
failure early in life. Coronary
revascularization is appropriate and feasible, although it
may be technically challenging due to abnormal conformation of the coronary
anatomy (5, 6).
1. Wissocque L, Mondesert B,
Dubart AE. Late diagnosis of
isolated congenitally corrected
transposition of the great arteries in a 92-year old woman. Eur
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[Epub ahead of print].
2. Warnes CA. Transposition of
the great arteries. Circulation
2006;114(24):26992709.
3. Solzbach U, Beuter M, Hartig
B, Haas H. Isolated dextrocardia
Figure 4. (a) Computed tomography of the heart with 3D rendering demonstrating the course of the coronary arteries as
with situs solitus (dextroversion).
they supply blood to the systemic ventricle (SV). (b) A fully rendered 3D representation of the heart shows the relationship
Herz 2010;35(3):207210.
between the SV and the pulmonary ventricle (PV) as well as the left anterior descending (LAD). (c) A short-axis view of the 4. Ismat FA, Baldwin HS, Karl
heart demonstrates that the aorta (Ao) is positioned anterior to the pulmonary artery (PA); (d) rather than being oriented
TR, Weinberg PM. Coronary
90 to each other, they are oriented in parallel.
anatomy in congenitally corrected transposition of the great
arteries. Int J Cardiol 2002;86(2
3):207216.
The approach to evaluating a patient with dextrocardia,
5. Baltalarli A, Tanriverdi H, Goksin I, Onem G, Rendeci O, Sacar M.
once the condition has been identied, should include idenCoronary arterial revascularization in an adult with congenitally cortication of visceral situs, atrioventricular concordance, venrected transposition of great arteries and dextrocardia. J Card Surg
tricular morphology and situs, relation of the great arteries,
2006;21(3):296297.
6. Mehrotra P, Choi JW, Flaherty J, Davidson CJ. Percutaneous coronary
and nally associated abnormalities (4). Imaging modalities
intervention in a patient with cardiac dextroversion. Proc (Bayl Univ Med
such as echocardiography, cardiac computed tomography,
Cent) 2006;19(3):226228.
April 2016
Isolated congenitally corrected transposition of the great arteries with dextroversion discovered incidentally
173
Invited Commentary
The specialty of adult congenital heart disease
ver the last three decades, adults with congenital heart

disease (ACHD) have become one of the fastest growing populations of adults with chronic heart disease.
Despite signicant progress in laying the foundations
to meet the rising care needs for ACHD patients, limited access to care and suboptimal data are impediments to continued
progress. The successes of pediatric cardiologists and surgeons
have permitted individuals with conditions that previously
would have been lethal in childhood to live and thrive well
into adulthood. This fact, in combination with improvements in
imaging technology permitting identication of clinically silent
lesions, has led to rapid growth in the numbers of patients with
ACHD in the general population (1, 2). This success, however,
has created a unique challenge to the eld of cardiology. Adult
cardiologists are not required by the Accreditation Council for
Graduate Medical Education (ACGME) to have specic training in caring for patients with congenital heart disease. As a
result, most adult cardiologists lack adequate familiarity with
congenital cardiac problems to provide optimal care. ACGME
requirements for pediatric cardiology training, in contrast, focus
on congenital heart disease and require fellows to have experience specically in ACHD. Nevertheless, pediatric cardiologists
have limited exposure to cardiologic issues common in adult
patients, such as coronary vascular disease or the cardiovascular
eects of cocaine abuse, for example.
In recognition of the need for a uniquely trained cadre of
individuals to care for this population, the ACGME has recently
created a training pathway for ACHD, open to both pediatric
and adult cardiologists, and ACHD is now recognized as a
subspecialty of both pediatric and adult cardiology. In addition, the most recent guideline statement from the American
College of Cardiology and American Heart Association on the
management of patients with ACHD recommends that patients
with all but the most simple of lesions be evaluated by ACHD
specialists (3). The benets of these recommendations were
demonstrated in a recent population-based study from Quebec,
Canada, in which referrals for ACHD specialty care resulted
in decreased mortality rates (4). As rates of hospitalization and
inpatient care costs among ACHD patients continue to grow
and the ACHD population ages, the importance of access to
ACHD-trained practitioners will increase (58).
To meet the growing needs to serve the ACHD population,
more ACHD-trained specialists are needed. In 2009, there were
just over 2000 board-certied or -eligible pediatric cardiologists
in the United States (9). In contrast, only approximately 200 examinees sat for the rst ACHD board exam in October 2015. In
the US and Canada, however, it is estimated there are now more
adults than children living with congenital heart disease (2, 3).
174
In addition to meeting the growing demand for clinical

care, more ACHD specialists are needed to broaden the therapeutic options available to improve outcomes in this unique
population. The few well-conducted, randomized, placebocontrolled trials in ACHD have failed to demonstrate the
ecacy of modern neurohumoral modulation in improving
outcomes in ACHD patients (1016). Although these failures may indicate inecacy of the tested medications, trends
present in these studies suggest that patient heterogeneity and
inadequate study power may have contributed to their failure.
Continued progress demands cooperation between providers
to optimize patient recruitment and to identify novel ACHDspecic outcomes with greater sensitivity to clinical changes
in this population.
It is essential that adult cardiologists make good on the
promises implied by the successes of our pediatric colleagues,
to improve quality and quantity of life for ACHD patients. To
achieve this goal, the cardiology community must encourage
fellowship training in ACHD, increase cooperation between
providers, and increase awareness of the importance of diseasespecic care. In this way we can continue to make a major
dierence in the lives of some of the greatest medical success
stories of the last century.
Ari M. Cedars, MD
E-mail: acedars97@gmail.com
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Consumption) study. Circulation 2014;130(23):20212030.
The specialty of adult congenital heart disease
175
Surgical considerations for the explantation of the Parachute

left ventricular partitioning device and the implantation of
the HeartMate II left ventricular assist device
Yazhini Ravi, MD, Shelley Bansal, MD, Paola C. Rosas, MD, PhD, RPh, Ernest L. Mazzaferri Jr., MD,
and Chittoor B. Sai-Sudhakar, MD
Chronic heart failure is the leading cause of death in the world. With
newer therapies, the burden of this disease has decreased; however,
a significant number of patients remain refractive to existing therapies.
Myocardial infarction often leads to ventricular remodeling and eventually
contributes to heart failure. The ParachuteTM (Cardiokinetix, Menlo Park,
CA) is the first device designed for percutaneous ventricular restoration therapy, which reduces left ventricular volume and minimizes the
risk of open surgical procedures. For the first time, we report a case of
explantation of the Parachute ventricular partitioning device and transition to a HeartMate IITM left ventricular assist device and the surgical
considerations for a successful outcome.
hronic heart failure (HF) patients with previous anterolateral myocardial infarction resulting in anteroapical
regional wall motion abnormality have been treated
with the Cardiokinetix Parachute ventricular partitioning device (VPD), which is deployed percutaneously in the left
ventricular (LV) cavity to the dysfunctional region (1). While
the data from the trial demonstrate improved outcomes, a small
percentage of patients continue to deteriorate symptomatically
(2, 3). This necessitates consideration for advanced surgical
therapies for HF, including heart transplantation and longterm mechanical circulatory support (2, 3). The presence of a
VPD and the static LV chamber pose surgical challenges during
placement of long-term devices. We report our experience in
the successful removal of the VPD and implantation of a left
ventricular assist device (LVAD).
CASE REPORT
A 57-year-old woman with a longstanding history of HF
due to morbid obesity was not considered to be a candidate for heart transplantation. She also had hypertension,
hyperlipidemia, chronic obstructive pulmonary disease, and
depression. She presented with severe chest pain, fatigue,
and dizziness and a prior history of numerous percutaneous
interventions on the coronary vasculature. In 2009, due to
progression of HF, the patient had successful VPD placement.
Postimplant, her ejection fraction improved from 15% to
25% with subjective improvement of HF symptoms. However, 24 months after VPD placement, she presented in New
176
York Heart Association class IV HF, and an echocardiogram

demonstrated an ejection fraction of <15%. After stabilization with inotropic therapy, the patient underwent a sternotomy, explantation of the VPD, and implantation of an
LVAD (HeartMate IITM, Thoratec, Pleasanton, CA) without
any complications.
A year after the LVAD was placed, it was explanted because it
clotted o. The patient survived this incident. Interestingly, she
did well for a period of time, but in 2014, she had multiple admissions for HF and was once again screened for the Parachute
USA trial. As there were no exclusion criteria for prior LVAD,
nor prior Parachute implantations, she was reenrolled (phase
3), and a Parachute device was placed successfully. This patient
had the rst-ever reimplant of a VPD. She has subsequently
done well and is presently listed in class 2 HF.
DISCUSSION
The Parachute device is made of a self-expanding nitinol
frame, an expanded polytetrauoroethylene impermeable occlusive membrane, and a polymer foot. The Parachute system
encompasses the device, balloon, and a delivery system consisting of the catheter and dilator (4). The frame has a conical shape,
which has 16 struts, the tips of which have anchors. The anchors
stabilize the device in the myocardium. However, these struts
have the potential to be rmly adherent to the myocardium
after deployment in the LV chamber. Moreover, it is conceivable
that the excluded portion of the LV chamber between the VPD
and the scarred area of the LV wall harbors a static column of
blood, which could lead to thrombus formation (4). The foot
is radio-opaque and aids visualization for proper placement of
the device under uoroscopy (3).
A median sternotomy is performed and the patient is
fully heparinized. Ascending aortic cannulation is carried
From the Division of Cardiothoracic Surgery, Department of Surgery, Baylor
Scott and White Health, Temple, Texas (Ravi, Sai-Sudhakar); Department of
Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida (Bansal); Department
of Medical Physiology, Texas A&M University Health Science Center, College of
Medicine, Temple, Texas (Rosas); and Department of Cardiology, The Ohio State
University, Columbus, Ohio (Mazzaferri).
Corresponding author: Yazhini Ravi, MD, 747 Brindley Circles, 2401 S. 31st
Street, Temple, TX 76508 (e-mail:Yazhini.ravi@bswhealth.org).
Figure. Outer surface of the Parachute device showing the areas of thrombus
formation and the anchors (struts) with fibrous overgrowth.
out by placing an Embol-X (Edwards LifeSciences, Irvine,

CA) aortic cannula in the ascending aorta and a dual-stage
venous cannula in the right atrium. The size of the ascending aorta is measured and the appropriately sized specialized
net is selected and placed through the side port of the aortic
cannula and deployed in the ascending aorta. The power
source of the LVAD is disconnected and the patient is immediately placed on a full cardiopulmonary bypass circuit.
The deployment of the appropriately sized net in the ascending aorta facilitates the capture of any particulate embolic
debris that may potentially be dislodged from the LV cavity
due to altered flow dynamics in the chamber secondary to
discontinuation of LVAD support and initiation of cardiopulmonary bypass. The aorta is cross-clamped. After the
patient is placed in a steep Trendelenburg position, the left
ventricle is brought into the midline and the apex is cored.
Care should be taken to ensure that in the process of LV wall
coring, the membranous portion of the VPD is not dam-
April 2016
aged by the coring device and hence the problem of distal

embolization is avoided.
It is imperative to perform a thorough evaluation of the LV
chamber excluded by the VPD. This is the region of the LV
chamber bounded by the LV scarred akinetic portion and the
outer surface of the VPD. The potential for clot formation in
this region is signicant due to factors including the akinetic
nature of the chamber walls and the absence of washout in the
space excluded by the VPD (Figure). The clot is carefully evacuated through the cored out LV apex.
The self-expanding nitinol frame of the VPD is tipped
with pointed barbs which, after initial deployment, are rmly
embedded in the LV free wall and septum with development
of brous tissue around the end regions of the nitinol frame.
A gentle inward pressure on each strut of the nitinol frame
toward its center dislodges the struts from the LV points of
embedment. Subsequently, the VPD is explanted through the
LV apex. The outside of the LV wall and ventricular septum are
carefully inspected to ensure the absence of partial or full thickness lacerations. The LVAD is then implanted, and the patient
is gradually weaned o cardiopulmonary bypass and placed
on LVAD support. Prior to decannulation, the net deployed
through the aortic cannula is removed and evaluated for the
presence of particulate debris.
1.
2.
3.
4.
Abraham WT. Could the ParachuteTM ventricular partitioning device

be a winner in the ght against heart failure? Expert Rev Cardiovasc Ther
2013;11(3):263265.
Costa MA, Mazzaferri EL Jr, Sievert H, Abraham WT. Percutaneous ventricular restoration using the Parachute device in patients with ischemic
heart failure: three-year outcomes of the Parachute rst-in-human study.
Circ Heart Fail 2014;7(5):752758.
Costa MA, Pencina M, Nikolic S, Engels T, Templin B, Abraham WT.
The Parachute IV trial design and rationale: percutaneous ventricular
restoration using the Parachute device in patients with ischemic heart
failure and dilated left ventricles. Am Heart J 2013;165(4):531536.
Sousa P, Bettencourt N, Ferreira N, de Jesus I, da Gama V. Left ventricular
partitioning device (Parachute): a multi-modality imaging perspective.
Eur Heart J Cardiovasc Imaging 2014;15(2):225.
Surgical considerations for the explantation of the Parachute left ventricular partitioning device
177
Intracranial aneurysm and sildenafil

Avinash Adiga, MD, Hawa Edriss, MD, and Kenneth Nugent, MD
Sildenafil is one of the most commonly used drugs for the treatment of
erectile dysfunction. To date, we found five reported cases of intracerebral
bleeding and two reported cases of subarachnoid hemorrhage related to
sildenafil use. We report a 49-year-old hypertensive and diabetic patient
who presented with acute pulmonary edema and loss of consciousness
following ingestion of 100 mg of sildenafil prior to sexual intercourse.
He was not previously aware of the presence of an aneurysm and had
no family history of it. Computed tomography of his head revealed a
subarachnoid hemorrhage due to rupture of a saccular aneurysm with
subsequent repeat hemorrhage within a few hours of presentation. A
sudden increase in blood pressure led to pulmonary edema. Studies have
shown that sildenafil acts on phosphodiesterase-1, -2 and -5 receptors
and leads to a secondary increase in intracerebral circulation and vasodilatory effects, leading to sympathetic overactivity which increases the
risk for intracranial bleeding.
ildenal, marketed as Viagra, is a widely used phosphodiesterase (PDE)-5 inhibitor to treat male sexual/erectile
dysfunction and to increase libido and sexual performance. The common adverse eects of this drug include
headache, ushing, indigestion, and impaired vision. Five cases
of intracerebral bleeding and two cases of subarachnoid hemorrhage (SAH) due to sildenal use have been reported (17). We
report a 49-year-old man who presented with a hypertensive
crisis and an SAH caused by rupture of a saccular intracranial
aneurysm during sexual intercourse following sildenal intake.
CASE REPORT
A 49-year-old man with diabetes mellitus and hypertension
was brought in to the emergency department due to acute-onset
shortness of breath and loss of consciousness during sexual intercourse. The patient had ingested 100 mg of sildenal prior to the
event (unknown time gap). Reportedly, he was diaphoretic and
short of breath and required intubation due to a low Glasgow
Coma Scale score of <7. His blood pressure was 181/105 mm
Hg with a mean arterial pressure of 124 mm Hg. His chest
examination revealed bibasilar crackles. A neurological examination was not completed because the patient was sedated. His pupils were round and reactive with normal deep tendon reexes,
and he could localize the pain. Routine blood counts, platelet
178
counts, and coagulation factors were normal. His chest x-ray

revealed diuse bilateral opacities consistent with pulmonary
edema. An electrocardiogram showed a normal sinus rhythm.
An arterial blood gas showed high anion gap (29) metabolic
acidosis with respiratory acidosis: pH 7.22; partial pressure of
oxygen, 68 mm Hg; partial pressure of carbon dioxide, 42.7
mm Hg; bicarbonate, 17.1 mEq/L; and lactate, 4.7 mmol/L.
Bedside transthoracic echocardiography showed normal systolic
function with no regional wall motion abnormality and grade
II diastolic dysfunction.
Computed tomography of the head showed a massive acute
SAH with the largest blood collection in the area of the anterior
communicating artery with mild hydrocephalus (Figure 1a).
The patient was started on mannitol 100 g over 30 minutes
and underwent computed tomography angiogram of intracranial vessels, which showed an aneurysm at the junction of the
right anterior cerebral artery and anterior communicating artery (Figure 1b). He was urgently taken to the operating room
and underwent ventriculostomy. While in the operating room,
his ventricular pressures increased, his pupils dilated, suggesting brain herniation, and he underwent bilateral decompressive craniotomy and aneurysm clipping. Postoperatively, his
Glasgow Coma Scale score was 3/15, and he was cooled to
maintain temperature around 35C for 48 hours. Because of
his low Glasgow Coma Scale score, his chances for safe extubation seemed unlikely, and a tracheostomy and percutaneous
endoscopic gastrostomy tube were placed on postoperative day
8. On postoperative day 10, he started to improve slowly, and
his Glasgow Coma Scale increased to 15/15 on postoperative
day 31. He continued to require a tracheostomy collar and was
discharged to a neurorehabilitation institute.
DISCUSSION
Sildenal inhibits PDE-5mediated hydrolysis of cyclic
guanosine monophosphate (cGMP), leading to increased
intracellular cGMP levels in the vascular smooth muscle of
the corpus cavernosum and resulting in smooth muscle relaxation and arterial vasodilation (8). The amount of cGMP in
From Texas Tech University Health Science Center, Lubbock, Texas.
Corresponding author: Avinash Adiga, MD, Texas Tech University Health Science
Center, 3601 4th Street, Lubbock, TX 79430 (e-mail: avinash.adiga@ttuhsc.edu).
Figure 1. (a) Computed tomography demonstrating a subarachnoid hemorrhage. (b) Computed tomography angiography showing an anterior carotid artery aneurysm.
cerebrovascular smooth muscles is aected by nitric oxide and

PDE. Nitric oxide activates guanylate cyclase in the cerebral
arterial cells. The activated guanylate cyclase converts guanosine
triphosphate to cGMP. The latter causes relaxation of vascular
smooth muscle cells in the cerebral vasculature (9, 10).
The relationship between intracranial hemorrhage (ICH)
and sildenal use is likely due to increased blood ow to the
intracranial vessels, which is signicantly increased during sexual
intercourse. Increased blood ow to the cerebral blood vessels
facilitates rupture of the cerebrovascular vessels in patients with
other hemorrhagic risk factors (3). Ballard et al suggested that
sildenal also acts on PDE-1 and PDE-2, which are involved
in controlling cerebral circulation (11). Studies on mice have
demonstrated that sildenal decreases cerebral vasospasm by
increasing and restoring cGMP levels (12). The reported adverse eects of sildenal include headache, visual disturbances,
pupil-sparing third nerve palsy, and transient hypertension, and
these symptoms suggest that sildenal also aects brain microvasculature regulation (13, 14). Unusual susceptibility to this
drug could lead to abnormal vasodilatation of cerebral arteries
and abnormal redistribution of arterial blood ow in the brain.
The hypothetical relationship between ICH and sildenal
ingestion is not well understood (2, 5). Transcranial Doppler
studies have shown that sildenal increases cerebrovascular reactivity and causes vasodilation with increased blood ow and
volume (15). The vasodilatory eect of sildenal causes hypotension that could lead to an increase in sympathetic activity,
which might be the reason for secondary hypertension leading
to SAH, as occurred in our case. Ayberk et al reported a case of
intracerebral bleed in a healthy 35-year-old man 3 hours after
ingestion of 50 mg of sildenal without any sexual activity (5).
This supports our conclusion that sildenal results in reactive
sympathetic hyperactivity that leads to ICH regardless of the
presence or absence of other risk factors, such as hypertension
and sexual intercourse. Nevertheless, our known hypertensive
patient had an elevated blood pressure and SAH after sildenal
use. Whether the hypertensive crisis in this patient caused by
sildenal was secondary to sympathetic hyperactivity or sexual
intercourse or whether the ICH itself caused hypertension cannot be determined. Also, we do not know if there is a doserelated eect which causes ICH. All reported patients ingested
50 mg or more (Table 1).
Sildenal citrate has been shown to be safe in patients without
cardiovascular disease but is contraindicated in those with acute
coronary syndromes, life-threatening coronary arrhythmias, and
recent stroke. The US Food and Drug Administration advises
Table 1. Reported cases of subarachnoid hemorrhage after sildenafil use

Variable
Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Our case
Age (years)
62
44
62
67
35
49
33
49
Hypertension
Yes
No
Yes
No
No
Unknown
No
Yes
Dose of sildenafil (mg)
50
4 tablets
(unknown strength)
50
50
50
Unknown
50
100
15/15
15/15
15/15/drowsy
Deceased
15/15
15/15
15/15
15/15
12/15
15/15
Dead on
arrival
3/15
Unknown
Low/intubated
15/15
Thalamic and
capsular
Left temporal
Right
subthalamic
Left temporal
subcortical
Caudate
nucleus
Left ACA,
SAH
Rightbasal
ganglia, SAH
Right ACA,
SAH
GlasgowComaScale:
admissionanddischarge
Type of bleed
ACA indicates anterior cerebral artery; SAH, subarachnoid hemorrhage. Cases appear in references 17.
April 2016
Intracranial aneurysm and sildenafil
179
cautioned use of sildenal in patients with a history of myocardial infarction or stroke within 6 months and those with
resting hypotension, severe hypertension (<170/110 mm Hg),
and heart failure (16).
All ve previously reported intracerebral hemorrhages with
sildenal use presented with minimal volume hemorrhage in
elderly patients with a risk factor of ICH, and surgical evacuation
was not required (Table 1) (15). However, the previous two reports of SAH with sildenal use were associated with severe bleeding (6, 7). One patient required emergency decompression due
to impending herniation, and the other patient was pronounced
dead on arrival (6, 7). Our patient rebled following the initial
SAH and underwent ventriculostomy and bilateral decompressive craniotomy. His neurological status improved tremendously,
and his Glasgow Coma Scale score was 15/15 on discharge. In
conclusion, sildenal is a relatively safe and widely used medication to treat erectile dysfunction. However, serious complications,
such as severe ICH and SAH, have been reported with its use.
1.
2.
3.
4.
5.
180
Alpsan MH, Bebek N, Ciftci FD, Coban O, Bahar S, Tuncay R. Intracerebral hemorrhage associated with sildenal use: a case report. J Neurol
2008;255(6):932933.
Buxton N, Flannery T, Wild D, Bassi S. Sildenal (Viagra)-induced spontaneous intracerebral haemorrhage. Br J Neurosurg 2001;15(4):347349.
Mart I, Mart Mass JF. Hemiballism due to sildenal use. Neurology
2004;63(3):534.
Monastero R, Pipia C, Camarda LK, Camarda R. Intracerebral haemorrhage associated with sildenal citrate. J Neurol 2001;248(2):141142.
Ayberk G, Ozveren MF, Yaman ME, Tosun H. Intracerebral hemorrhage after
sildenal citrate use: an incidental association? Urol J 2014;11(2):15241526.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Byoun HS, Lee YJ, Yi HJ. Subarachnoid hemorrhage and intracerebral

hematoma due to sildenal ingestion in a young adult. J Korean Neurosurg
Soc 2010;47(3):210212.
De-Giorgio F, Arena V, Arena E, Arena E, Lodise M, Valerio L, dAloja
E, Chiarotti M. Subarachnoid hemorrhage during sexual activity after
sildenal intake: an accidental association? Am J Forensic Med Pathol
2011;32(4):310311.
McHugh J, Cheek DJ. Nitric oxide and regulation of vascular tone:
pharmacological and physiological considerations. Am J Crit Care
1998;7(2):131140.
Inoha S, Inamura T, Ikezaki K, Nakamizo A, Amano T, Fukui M. Type
V phosphodiesterase expression in cerebral arteries with vasospasm after
subarachnoid hemorrhage in a canine model. Neurol Res 2002;24(6):607
612.
Sobey CG, Quan L. Impaired cerebral vasodilator responses to NO
and PDE V inhibition after subarachnoid hemorrhage. Am J Physiol
1999;277(5 Pt 2):H1718H1724.
Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM. Effects of sildenal on the relaxation of human corpus cavernosum tissue in
vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes.
J Urol 1998;159(6):21642171.
Han BH, Vellimana AK, Zhou ML, Milner E, Zipfel GJ. Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage. Neurosurgery
2012;70(1):178186.
Donahue SP, Taylor RJ. Pupil-sparing third nerve palsy associated with
sildenal citrate (Viagra). Am J Ophthalmol 1998;126(3):476477.
Vobig MA, Klotz T, Staak M, Bartz-Schmidt KU, Engelmann U, Walter
P. Retinal side-eects of sildenal. Lancet 1999;353(9150):375.
Brenner S, Diomedi M, Sallustio F. Sildenal increases cerebrovascular
reactivity: a transcranial Doppler study. Neurology 2006;66(9):1455
1456.
Kloner RA, Jarow JP. Erectile dysfunction and sildenal citrate and cardiologists. Am J Cardiol 1999;83(4):576582, A7.
Volume 29, Number 2
Infective endocarditis caused by Klebsiella oxytoca in an

intravenous drug user with cancer
Ashref Mohamed, MD, Connor Hall, MS, PhD, Michael Hatch, MS, Mohamed Ayan, MBBCh, and Richard Winn, MD
Infective endocarditis caused by Klebsiella species is rare, with most

isolates being K. pneumoniae. We report the case of a 24-year-old intravenous drug user with newly diagnosed seminoma who developed K.
oxytoca endocarditis. In addition to having K. oxytoca isolated from blood
culture, cultures of that species were obtained from a retroperitoneal
metastasis found on original presentation.
nfective endocarditis caused by Klebsiella species is a rare

event, accounting for 1.2% cases of native valve endocarditis and up to 4.1% cases of prosthetic valve endocarditis
(1). Of these, most are caused by K. pneumoniae. K. oxytoca
is implicated in a signicant minority of endocarditis cases
caused by Klebsiella species, with only 5 reported cases (26).
Most cases of K. oxytoca endocarditis occur in the elderly and
are nosocomial. Here we report a case of community-acquired
K. oxytoca in an intravenous drug abuser coinciding with newly
diagnosed testicular cancer.
CASE PRESENTATION
A 24-year-old man presented to the emergency department
with a 1-week history of uctuating back and ank pain associated with fever. He rst presented to an outside hospital after experiencing sudden-onset fever, chills, sweats, pallor, and dyspnea.
At that visit, his temperature was 102F, and a computed tomography (CT) scan of the abdomen without contrast revealed a large
perinephric mass. The patient was sent to our facility for further
management. In the emergency department, his blood pressure
was 107/65 mm Hg; heart rate, 116 beats/minute; respiratory
rate, 16 breaths/minute; and temperature, 97.7F. Examination
revealed right upper-quadrant tenderness on deep palpation and
normal heart sounds with no murmur. His electrocardiogram
was unremarkable. His hemoglobin was 12.2 g/dL; white blood
cell count, 21,890/uL; alkaline phosphatase, 489 IU/L; aspartate
aminotransferase, 199 IU/L; and alanine aminotransferase, 223
IU/L. Blood cultures were obtained and he was started on empiric
vancomycin and meropenem for concerns of abscess and sepsis.
Repeat CT scan with contrast conrmed a peripherally
enhancing right retroperitoneal mass measuring 6.4 7.5 9.1
cm with central hypodensity, suggestive of a necrotic lymph node
and concerning for malignancy (Figure 1). A 12 French drain-
Figure 1. CT scan of the abdomen with contrast showing a retroperitoneal mass

with abscess formation.
age catheter was placed, and 80 mL of purulent thick uid was

aspirated and submitted for gram stain, cultures, and cytology.
An additional 160 mL of uid was drained over the next 3 days.
On follow-up, he reported having a 3-month history of an
enlarging testicular mass. Following ultrasound concerning for
malignancy, a radical right orchiectomy was performed showing classic seminoma, and further imaging staged the cancer as
stage IIIB due to involvement of retroperitoneal and mediastinal lymph nodes. Meanwhile, blood cultures obtained in the
emergency department as well as the outside hospital revealed
growth of K. oxytoca. Vancomycin was discontinued.
On hospital day 5, the patients fever spiked to 102.9F,
and a holosystolic murmur most prominent over the apex was
discovered. At this point, the patient admitted to injection of
amphetamines diluted with tap water 1.5 weeks prior to admission. Transesophageal echocardiogram revealed 0.44 0.17 cm
vegetation on the posterior mitral valve leaet (Figure 2). In
From the Department of Internal Medicine, Texas Tech University Health Science
Center, Lubbock, Texas (Mohamed, Hall, Hatch, Winn); and Creighton University
Medical Center, Omaha, Nebraska (Ayan).
Corresponding author: Ashref Mohamed, MD, Department of Internal Medicine,
Texas Tech University Health Science Center, 3601 4th Street, Lubbock, TX 79430
(e-mail: ashref.mohamed@ttuhsc.edu).
181
Figure 2. Transesophageal echocardiogram revealing 0.44 0.17 cm vegetation

on the posterior mitral valve leaflet.
addition, CT-guided drainage of the retroperitoneal mass grew

K. oxytoca and also contained malignant cells. Repeat CT scan
4 days after drain placement showed a reduction in mass size
to 5.5 5.0 8.0 cm. The patients fever abated, and follow-up
blood cultures were negative. Intravenous meropenem was continued for 6 weeks with no complications. No follow-up echocardiogram was performed as the patient was lost to follow-up.
DISCUSSION
This is a rare case of infective endocarditis of the mitral valve
caused by K. oxytoca in an intravenous drug user. The diagnosis
of infective endocarditis is based on the modied Duke criteria:
one major criterion (intracardiac mass on the mitral valve) and
three minor criteria (fever, positive blood culture, and predisposing intravenous drug use) (7). K. oxytoca endocarditis is extremely rare. The ve reported cases are summarized in Table 1
(26). Of those cases, two were community acquired, as was
Table 1. Previously reported cases of infective endocarditis

caused by Klebsiella oxytoca
Case (ref)
Age/sex Presentation Mode of entry Treatment
Watanakunakorn, 87 M
1985 (2)
UTI,
bacteremia,
IE
After
transurethral
resection of
the prostate
Cefazolin,
tobramycin
Repiso et al,
2001 (3)
33 M
Bacteremia,
IE (BP PV)
Intravenous
drug user
Cefotaxime,
gentamicin
Chen et al, 2006

(4)
71 F
Bacteremia,
IE (MV)
Community
acquired, unknown mode
of entry
Cefazolin
de Escalante
et al, 2007 (5)
75 M
Bacteremia,
IE (AV)
Following AAA Imipenem,

repair
gentamicin
Duggal et al,
2012 (6)
66 M
Bacteremia,
IE (BP AV)
Ceftriaxone,
Community
gentamicin
acquired,
unknown
mode of entry
AAA indicates abdominal aortic aneurysm; AV, aortic valve; BP, bioprosthetic; IE, infective
endocarditis; MV, mitral valve; PV, pulmonary valve; UTI, urinary tract infection.
182
this case (4). Fortunately, K. oxytoca endocarditis appears to

have favorable outcomes, as reported cases show resolution with
antibiotics alone (2, 4, 6). In contrast, K. pneumoniae endocarditis has a 49% mortality rate, and 44% of patients ultimately
require valve replacement (1). K. oxytoca is an opportunistic
gram-negative rod that is dierentiated from K. pneumoniae
by its indole positivity.
Intravenous drug use is a signicant risk factor for the development of infective endocarditis and a probable mode of entry
in this patient, who had a history of injecting tap water-diluted
intravenous drugs (8). Over 90% of infectious endocarditis cases
in intravenous drug users are caused by gram-positive cocci,
specically staphylococci or streptococci, but other organisms
are possible (9). In addition, neoplasia is a predisposing factor
for developing K. oxytoca bacteremia (10). It is possible that this
patient had prior metastatic spread of his seminoma to a retroperitoneal lymph node. He then seeded his blood with K. oxytoca
through the injection of amphetamines diluted in tap water,
where the bacteria then simultaneously colonized the necrotic
lymph node and mitral valve, colonized the mitral valve with
subsequent septic embolization to the lymph node, or colonized
the necrotic lymph node with subsequent colonization of the
mitral valve. Documented modes of entry for K. oxytoca in cases
of bacteremia include, in descending order, the hepatobiliary
tract (50%55%), intravascular or urinary catheters (7%16%),
the urinary tract (5%6%), skin and soft tissues (3%5%), and
the peritoneal cavity (2%6%), while 23% to 34% of infections
have no identiable ports of entry (10, 11). Therefore, dening
the precise route of entry in this patient is dicult, but intravenous drug use is strongly supported as the causal mechanism.
Anderson MJ, Jano EN. Klebsiella endocarditis: report of two cases and
review. Clin Infect Dis 1998;26(2):468474.
2. Watanakunakorn C. Klebsiella oxytoca endocarditis after transurethral
resection of the prostate gland. South Med J 1985;78(3):356357.
3. Repiso M, Castiello J, Repraz J, Uriz J, Sola J, Elizondo MJ. Endocarditis
caused by Klebsiella oxytoca: a case report. Enferm Infecc Microbiol Clin
2001;19(9):454455.
4. Chen JY, Chen PS, Chen YP, Lee WT, Lin LJ. Community-acquired
Klebsiella oxytoca endocarditis: a case report. J Infect 2006;52(5):e129e131.
5. de Escalante Yangela B, Aibar Arregui MA, Muoz Villalengua M, Olivera Gonzlez S. Klebsiella oxytoca nosocomial endocarditis. Med Interna
2007;24(11):563564.
6. Duggal A, Waraich KK, Cutrona A. Klebsiella oxytoca endocarditis in a patient with a bioprosthetic aortic valve. Infect Dis Clin Pract
2012;20(3):224225.
7. Hoen B, Duval X. Clinical practice. Infective endocarditis. N Engl J Med
2013;368(15):14251433.
8. Tung MK, Light M, Giri R, Lane S, Appelbe A, Harvey C, Athan E. Evolving epidemiology of injecting drug use-associated infective endocarditis:
a regional centre experience. Drug Alcohol Rev 2015;34(4):412417.
9. Mathew J, Addai T, Anand A, Morrobel A, Maheshwari P, Freels S. Clinical features, site of involvement, bacteriologic ndings, and outcome
of infective endocarditis in intravenous drug users. Arch Intern Med
1995;155(15):16411648.
10. Lin RD, Hsueh PR, Chang SC, Chen YC, Hsieh WC, Luh KT. Bacteremia
due to Klebsiella oxytoca: clinical features of patients and antimicrobial
susceptibilities of the isolates. Clin Infect Dis 1997;24(6):12171222.
11. Kim BN, Ryu J, Kim YS, Woo JH. Retrospective analysis of clinical and
microbiological aspects of Klebsiella oxytoca bacteremia over a 10-year
period. Eur J Clin Microbiol Infect Dis 2002;21(6):419426.
1.
Volume 29, Number 2
Rapidly enlarging neck mass in a neonate causing airway

compromise
Kyra Schmidt, BS, Andres Leal, MD, Thomas McGill, MD, and Roy Jacob, MD
Up to 20% of all congenital pediatric head and neck masses are branchial
cleft cysts. Second branchial cleft cysts account for 95% of branchial
anomalies, and fourth branchial cleft cysts are the rarest type. Their
typical presentations include nonlife-threatening symptoms, such as
drainage, skin irritations, minor swelling, and tenderness. We describe
a 5-week-old neonate with increasing stridor secondary to a rapidly
growing neck mass. Imaging and surgical excision confirmed the mass
to be an infected fourth branchial cleft cyst.
e describe a neonate with a neck mass causing airway

compromise. Branchial cleft anomalies comprise up
to 20% of all congenital pediatric head and neck lesions (1). Branchial cleft anomalies form when there
is an abnormality in the obliteration of the clefts in between
the branchial arches (2). Of these anomalies, fourth branchial
cleft anomalies are rarest and are typically found in the lower
third of the neck on the left side (2, 3). Discovery often occurs
after infection of the cyst and resultant suppurative thyroiditis
(4). Fourth cleft cysts have been reported to occur at any age,
including in utero. Typically, branchial cleft cysts have nonlifethreatening symptoms including drainage, skin irritation, minor
swelling, and tenderness, but if infected can result in diculty
swallowing and breathing due to mass eect.
CASE DESCRIPTION
A 5-week-old neonate was brought to the emergency department with diculty breathing and a left-sided neck mass.
The mother reported that the infant had increased diculty
breathing at night and when crying for the past 1 week. He
also had vomiting for 1 week with decreased appetite. The mass
had been noticed 4 weeks earlier and had been progressively
increasing in size. The child was alert and comfortable at rest
in the mother's arms. However, when placed supine, he became
agitated and exhibited stridor and respiratory distress. A 5
4 cm mass was identied on the left side of the neck, crossing
the midline (Figure 1).
An ultrasound of the neck showed a mass with heterogeneous
echogenicity with predominantly solid components and minimal
vascularity (Figure 2). Computed tomography (CT) of the neck
with intravenous contrast demonstrated a nonenhancing mass
Figure 1. Five-week-old with mass in left side of neck and resulting rightward
shift of the trachea.
Figure 2. Ultrasound shows a solid mass in the left side of the neck with minimal
vascularity.
From the Texas Tech University Health Sciences Center School of Medicine
(Schmidt); and the Departments of Surgery (Leal, McGill) and Radiology (Jacob),
Texas Tech University Health Sciences Center School of Medicine, Lubbock, Texas.
Corresponding author: Roy Jacob, MD, Department of Radiology, University
Medical Center, Texas Tech University, 602 Indiana Avenue, Lubbock, TX 79415
(e-mail: roy.jacob@ttuhsc.edu).
183
(59). In this case, CT imaging was useful in determining the

extent of the mass and identied structures at risk during excision. It also showed the involvement of the left lobe of the
thyroid gland.
Treatment of branchial cleft cysts is complete excision after
infancy, to prevent recurrent infection and abscess formation
as well as mass eect on local structures (1012). Airway compromise and respiratory distress are indications for emergent
surgery. This case illustrates that fourth branchial cleft cysts can
rapidly increase in size and compromise the airway and should
be considered in the dierential diagnosis while evaluating a
neonatal neck mass.
1.
Figure 3. CT of the neck shows the mass involving the left lobe of the thyroid
gland along with mass effect and rightward displacement of the trachea.
in the left side of the neck at the base with involvement of the
left lobe of the thyroid gland as well as signicant compression
of the trachea (Figure 3). The mass was excised, and histologic
study disclosed it to be a fourth branchial cleft cyst.
DISCUSSION
When presented with a neck mass in a neonate, dierentials include rhabdomyosarcoma, teratoma, venolymphatic
malformations, bromatosis colli, and a branchial cleft cyst.
Venolymphatic malformations are typically soft, compressible,
and nonpulsatile. Clinical ndings are nonspecic in the other
dierentials.
Ultrasound and CT imaging were helpful in diagnosis.
While ultrasound has a low predictive power for third or
fourth branchial cleft anomalies, ultrasound imaging in this
case was used to eliminate venolymphatic malformations and
bromatosis colli from the dierential diagnosis (5). CT is the
most common diagnostic tool for branchial anomalies, with a
positive branchial anomaly identication rate as high as 64%
184
Go CJ, Allred C, Glade RS. Current management of congenital branchial cleft cysts, sinuses, and stulae. Curr Opin Otolaryngol Head Neck
Surg 2012;20(6):533539.
2. Waldhausen JH. Branchial cleft and arch anomalies in children. Semin
Pediatr Surg 2006;15(2):6469.
3. Nicoucar K, Giger R, Pope HG Jr, Jaecklin T, Dulguerov P. Management
of congenital fourth branchial arch anomalies: a review and analysis of
published cases. J Pediatr Surg 2009;44(7):14321439.
4. Nicollas R, Ducroz V, Garabdian EN, Triglia JM. Fourth branchial pouch
anomalies: a study of six cases and review of the literature. Int J Pediatr
Otorhinolaryngol 1998;44(1):510.
5. Nicoucar K, Giger R, Jaecklin T, Pope HG Jr, Dulguerov P. Management of congenital third branchial arch anomalies: a systematic review.
Otolaryngol Head Neck Surg 2010;142:2128; e2.
6. Schroeder JW Jr, Mohyuddin N, Maddalozzo J. Branchial anomalies in the
pediatric population. Otolaryngol Head Neck Surg 2007;137(2):289295.
7. Acierno SP, Waldhausen JH. Congenital cervical cysts, sinuses and stulae.
Otolaryngol Clin North Am 2007;40(1):161176, vii-viii.
8. Mitroi M, Dumitrescu D, Simionescu C, Popescu C, Mogoant C, Cioroianu
L, Surlin C, Cpitnescu A, Georgescu M. Management of second branchial
cleft anomalies. Rom J Morphol Embryol 2008;49(1):6974.
9. DSouza AR, Uppal HS, De R, Zeitoun H. Updating concepts of rst
branchial cleft defects: a literature review. Int J Pediatr Otorhinolaryngol
2002;62(2):103109.
10. Choi SS, Zalzal GH. Branchial anomalies: a review of 52 cases. Laryngoscope
1995;105(9 Pt 1):909913.
11. Reiter D. Third branchial cleft sinus: an unusual cause of neck abscess.
Int J Pediatr Otorhinolaryngol 1982;4(2):181186.
12. Ford GR, Balakrishnan A, Evans JN, Bailey CM. Branchial cleft and
pouch anomalies. J Laryngol Otol 1992;106(2):137143.
Volume 29, Number 2
Serendipitous discovery of peritoneal mesothelioma

Adam Jaster, MD, and Jason Wachsmann, MD
We present the case of a 64-year-old patient with a history of BirtHogg-Dube syndrome, polycystic kidney disease treated with renal
transplantation in May 2013, and multiple types of skin cancers,
including malignant melanoma. He presented for lymphoscintigraphy
for sentinel lymph node identification of the melanoma. Subsequent
biopsy of the right axillary sentinel lymph node yielded a diagnosis of
epithelial type malignant mesothelioma without a known primary tumor.
Follow-up positron emission tomography with 2-deoxy-2-(fluorine-18)
fluoro-D-glucose integrated with computed tomography (F-18 FDG
PET/CT) demonstrated several suspicious hypermetabolic abdominal
masses that were later confirmed to be epithelial-type mesothelioma
via percutaneous biopsy.
alignant mesothelioma is a rare tumor that originates from the cells lining the mesothelial surfaces,
including the pleura, peritoneum, pericardium,
and tunica vaginalis. The most common subtype of
mesothelioma is the pleural form (1). Malignant peritoneal
mesothelioma (MPM) accounts for about 12.5% to 25% of
malignant mesotheliomas and typically occurs in middle-aged
men with a variety of abdominal symptoms (2). MPM is a very
aggressive tumor that may present as either a localized or diuse
form. The diuse form typically is more aggressive and has a
worse prognosis (3).
CASE REPORT
A 64-year-old man presented to his dermatologist for a
new skin lesion in the anterior chest wall. He had a history of Birt-Hogg-Dube syndrome, polycystic kidney disease
treated with renal transplantation in May 2013, and multiple
types of skin cancers, including malignant melanoma. Shave
biopsy of the new lesion demonstrated melanoma. Subsequent lymphoscintigraphy performed with 55.5 Mbq of Tc99m sulfur colloid showed a right axillary sentinel lymph
node. The pathologic evaluation of this lymph node unexpectedly revealed malignant mesothelioma, epithelial type.
The patient then underwent computed tomography (CT)
of the chest, which was negative for thoracic mesothelioma.
In an attempt to locate the primary lesion, a whole body
Figure 1. Lymphoscintigraphy performed with 55.5 Mbq of Tc-99m sulfur

colloid showed a right axillary sentinel lymph node (arrow).
2-deoxy-2-(uorine-18)uoro-D-glucose positron emission

tomography (F-18 FDG PET) integrated with CT was performed. This showed abnormal radiotracer uptake within
two separate regions of the anterior abdominal wall, as well
as the right inguinal region. Uptake related to the excisional
biopsies of the melanoma and previously described right axillary sentinel lymph node were also noted (Figure 2). After a
diagnosis of MPM was made via percutaneous biopsy of an
anterior abdominal wall mass, a review of prior imaging was
performed. Magnetic resonance imaging (MRI) of the abdomen from November 2005 depicted an enhancing anterior
periumbilical mass (Figure 3).
DISCUSSION
The main risk factor for MPM is asbestos exposure; however, it is believed that this association is not as strong as
the one between asbestos exposure and pleural mesothelioma
From the Division of Nuclear Medicine and Molecular Imaging, Department of
Radiology, University of Texas Southwestern Medical Center, Dallas, Texas.
Corresponding author: Jason Wachsmann, MD, Department of Radiology,
University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas,
TX 75390-8896 (e-mail: Jason.Wachsmann@UTSouthwestern.edu).
185
Figure 2. (a) Whole-body MIP image from an F-18 FDG PET/CT demonstrates abnormal radiotracer uptake within the two separate regions of the anterior abdominal wall as well as the right
inguinal region (solid red arrows). Linear uptake in the right back and axilla (blue dashed arrows)
corresponds to the melanoma excision and axillary node dissection sites. (b) Sagittal whole-body
image from the same patient shows abnormal focal radiotracer uptake in two separate areas of
the anterior abdominal wall (white arrows). (c) Transaxial CT and (d) FDG-18 PET/CT images at
the level of the superiorly located abdominal wall mass show abnormal radiotracer uptake in the
midline anterior wall on FDG-18 PET/CT, which corresponds with the anterior abdominal wall mass
seen on CT (orange arrow). Also shown in these images are a right renal transplant (curved arrow)
and polycystic left kidney (thin arrow).
(4, 5). Other proposed risk factors include simian vacuolating virus, familial Mediterranean
fever, and mesothelioma susceptibility syndrome
with BRCA germline mutations. Classically this
tumor has a rapidly fatal course with a median
survival time of 6 to 12 months. Since the disease is rare, information regarding the exact incidence, natural history, and risk factors is limited.
Our patient had a history of Birt-Hogg-Dube
syndrome, which is a genetic syndrome that classically involves an increased incidence of renal
carcinoma, spontaneous pneumothorax, pulmonary cysts, and various skin lesions. However,
the syndrome does not have a known association
with mesothelioma.
The preliminary staging evaluation of peritoneal mesothelioma and subsequent follow-up
imaging can be performed with CT, MRI, or
FDG-PET. The evaluation of peritoneal mesothelioma by FDG-PET had an accuracy of 82%
in a large study that retrospectively evaluated 60
patients with this disease. This study also demonstrated that in 15 of these patients with a posttreatment negative FDG-PET study, subsequent
follow-up exams accurately detected disease recurrence or further disease absence in all cases (6).
Multiple other case reports have utilized FDGPET to assist in diagnosis, staging, and monitoring of therapy (7, 8).
MPM is classically a very rare and aggressive
tumor involving the peritoneum. Of all documented mesotheliomas, it is second to pleural
mesothelioma with an incidence of 10% to 30%.
The estimated incidence of this disease is 200 to
400 cases annually. Our case did not follow the
classic route in the workup of MPM.
Figure 3. (a) Precontrast and (b)

postcontrast transaxial spoiled
gradient echo MR images from
November 2005, which depict
an enhancing anterior periumbilical mass that was biopsied in
September 2014 and proven to
be epithelial-type peritoneal mesothelioma (red arrow). Changes
of polycystic kidney disease are
also shown in these images (green
arrows).
186
Volume 29, Number 2
1.
van Meerbeeck JP, Scherpereel A, Surmont VF Baas P. Malignant pleural

mesothelioma: the standard of care and challenges for future management.
Crit Rev Oncol Hematol 2011;78(2):92111.
2. Saraya T, Yokoyama T, Ishii H, Tanaka Y, Tsujimoto N, Ogawa Y, Sohara
E, Nakajima A, Inui T, Sayuki H, Fujiwara M, Oka T, Kawachi R, Goya
T, Takizawa H, Goto H. A case of malignant peritoneal mesothelioma
revealed with limitation of PET-CT in the diagnosis of thoracic metastasis
J Thorac Dis 2013;5(1):E11E16.
3. Ozguven S , Aras M , Dede F, Ones T Turoglu HT Scrotal peritoneal mesothelioma on PET/CT. Clin Nucl Med 2014;39(12):1045
1046.
4.
5.
6.
7.
8.
Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a

review. MedGenMed 2007;9(2):32.
Raza A, Huang WC, Takabe K. Advances in the management of peritoneal
mesothelioma. World J Gastroenterol 2014;20(33)1170011712.
Vilardell AD, Rasiej MJ, Taub RN, Ichise M. Clinical utility of 18F-FDG
positron emission tomography in malignant peritoneal mesothelioma. Q
J Nucl Med Mol Imaging 2014 Apr 14 [Epub ahead of print].
Cao Q, Lu M, Heath J, Hausner PF, Alexander HR, Dilsizian V, Chen
W. 18F-FDG PET/CT in a recurrent diuse malignant peritoneal mesothelioma. Clin Nucl Med 2012;37(5):492494.
Nguyen BD. PET/CT demonstration and monitoring of thoracic and
abdominal wall mesothelioma. Clin Nucl Med 2014;39(1) e106e109.
Avocations
Indian Paintbrush blossom. Photo by Rolando M. Solis, an interventional cardiologist at Baylor Scott and White Health Garland and The Heart Hospital Baylor Plano.
He can be reached by e-mail at rmsolis@mac.com.
April 2016
Serendipitous discovery of peritoneal mesothelioma
187
Pneumomediastinum, pneumorrhachis, and subcutaneous

emphysema in Pneumocystis jiroveci pneumonia in AIDS
Nasir Saleem, MD, Sanober Parveen, MD, Chibuzo Odigwe, MD, and Nkemakolam Iroegbu, MD, MPH
Pneumomediastinum, the presence of free air within the mediastinal

cavity, is sometimes accompanied by subcutaneous emphysema and
pneumorrhachis (air within the spinal canal). We report the case of a
28-year-old man with previously undiagnosed HIV who was diagnosed
with extensive pneumomediastinum, pneumorrhachis, and subcutaneous emphysema secondary to Pneumocystis jiroveci pneumonia after
presenting with chest pain, dyspnea, and central cyanosis. Surgical consultation was requested, but a conservative approach of observation
proved sufficient as the free air was resorbed into the surrounding tissues.
neumocystis jiroveci pneumonia is a common opportunistic infection in patients with AIDS and low CD4 counts
<200 cells/mm3. In most cases, P. jiroveci pneumonia
presents with chest pain, cough, shortness of breath, and
hypoxemia. It has a high mortality rate unless treated promptly
with antibiotics and, if severe, steroids. Pneumatoceles that form
as a complication of P. jiroveci pneumonia can rupture, allowing
air to leak and spread along the peribronchial linings and facial
planes of the chest, neck, and axilla to give rise to subcutaneous
emphysema, pneumomediastinum, and in some severe cases
pneumorrhachis (13). Noninvasive imaging studies such as
chest x-ray and computed tomography (CT) scan of the chest
are usually enough to detect these ndings. Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema usually resolve spontaneously, and a conservative strategy of close
monitoring and observation may be sucient.
CASE REPORT
A 28-year-old man with no signicant past medical history
presented to the emergency department with substernal chest
pain, dyspnea, orthopnea, and central cyanosis of 1 week duration. The symptoms progressively worsened and became very
severe the night prior to his presentation. He reported fever,
malaise, fatigue, and mild cough productive of clear, whitish
sputum. He denied any trauma, allergies, sick contacts, recent
travels, or similar episodes in the past. He reported a weight loss
of about 90 lbs over the preceding year. The patient reported
that he had not been sexually active for the previous 9 months
but had been sexually active with both men and women and
used barrier protection inconsistently. On examination, he ap188
peared in moderate to severe distress and had central cyanosis,

with a pulse of 109 beats/minute, blood pressure of 132/79
mm Hg, temperature of 97.5F, respiratory rate of 26 breaths
per minute, and oxygen saturation of 76% on room air. He
was placed on a nonrebreather mask, and his oxygen saturation improved to 96% to 99%. There was minimal crepitus
on palpation of the neck and chest wall and scattered crackles
throughout both lungs.
Chest radiographs revealed diffuse bilateral opacities,
marked subcutaneous emphysema in the neck, and pneumomediastinum (Figure 1a). A subsequent CT scan of the chest
conrmed these ndings and also showed emphysema in the
axilla and pneumorrhachis (epidural pneumatosis) in the thoracic spinal canal (Figures 2). The patients HIV test was positive. Given the high suspicion for pneumocystis pneumonia
in the presence of HIV infection, the patient was started empirically on intravenous trimethoprim-sulphamethoxazole and
prednisone. Over the following 2 days, the dyspnea and chest
pain disappeared. He was transitioned to nasal cannula oxygen.
Subsequent chest radiographs revealed signicant improvement
in the extent of subcutaneous emphysema and pneumomediastinum (Figure 1b).
Once stable, the patient underwent bronchoscopy, and
bronchial washings conrmed the presence of P. jiroveci pneumonia on Gomori methenamine silver staining. Direct uorescent antibody on the bronchial washings also conrmed the
presence of P. jiroveci pneumonia. The patient had an HIV
viral load of 485,425/mm3 and CD4 count of 24. On day 5
of his hospitalization, he was switched to oral trimethoprimsulphamethoxazole and prednisone and was discharged in stable
condition to continue outpatient follow-up for reassessment and
preparation for initiating highly active antiretroviral therapy.
DISCUSSION
Spontaneous pneumomediastinumthe presence of free air
in the mediastinum without an obvious etiologyoccurs in 1 in
30,000 emergency department visits (1, 2). The co-occurrence
From the Department of Medicine, Presence St. Joseph Hospital, Chicago, Illinois.
Corresponding author: Chibuzo Odigwe, MD, Department of Medicine,
Presence St. Joseph Hospital, 2900 N. Lakeshore Drive, Chicago, IL 60657
(e-mail: chibuzo2k2@yahoo.com).
Figure 1. (a) Chest x-ray showing bilateral pulmonary infiltrates with prominent symmetrical pneumomediastinum (black arrow) associated with subcutaneous
emphysema in the base of the neck and along both shoulders (white arrows) and axilla (white arrowhead). (b) Chest x-ray, day 3, showing decreased amount
of pneumomediastinum (white arrow) and subcutaneous emphysema in the soft tissues of the neck. Air in the axillary regions is almost totally resorbed (white
arrowhead).
of spontaneous pneumomediastinum and pneumorrhachis is

rare, and few cases have been reported (35).
Spontaneous pneumomediastinum occurs with abrupt
transalveolar pressure gradient increases like a Valsalva maneuver, violent coughing, or intense physical exertion. The pathophysiologic process was described by Macklin in 1939 (6). The
Macklin eect refers to an alveolar rupture with air dissection
along the interstitial sheaths toward the mediastinum, eventually leading to a pneumomediastinum (7). Alveolar rupture is
responsible for more than 95% of cases and is a more frequent
cause than esophageal and tracheobronchial disruptions (7).
The clinical presentation of pneumomediastinum is benign
and self-limiting. The most common complaints are chest pain
and dyspnea; chest pain is commonly pleuritic and retrosternal.
CT of the chest is the gold standard for diagnosis. If suspicion
for aerodigestive tract perforation is high, a barium swallow,
a
esophagoscopy, or bronchoscopy may be performed. The management of patients with spontaneous pneumomediastinum is
conservative, consisting of rest, analgesics, and close observation. The utility of antibiotics, oxygen therapy, and restriction
of oral intake is debatable (1).
Although pneumomediastinum is benign, the risk of tension pneumomediastinum or pneumothorax justies close
clinical observation. Pneumopericardium may also occur, with
complications such as air tamponade and cardiac herniation
(8, 9). For the management of pneumomediastinum, Okada et
al (8) proposed that patients without (i) fever <38C, (ii) oxygen
desaturation <96%, (iii) progressive symptoms, (iv) vomiting
at the onset, and (v) anxiety should receive ambulatory care.
Pneumorrhachis is usually an asymptomatic radiologic
nding (9). Pneumorrhachis can be classied into traumatic,
nontraumatic, and iatrogenic types (4). Pneumorrhachis usually
b
Figure 2. (a) Chest CT scan and (b) mediastinal window showing bilateral ground-glass infiltrates, subcutaneous emphysema in the lateral chest wall and axillary
region (white arrowhead), free air surrounding mediastinal vascular structures (blue arrow), massive pneumomediastinum (white arrow), and free air in the thoracic
spinal canal (black arrow).
April 2016
Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema in Pneumocystis jiroveci pneumonia in AIDS
189
does not cause any symptoms and is commonly detected incidentally. Pneumorrhachis without associated trauma or intervention is rare (9, 10). There are few reports of combined
pneumomediastinum and extradural pneumorrhachis not associated with trauma (9, 10). Our patient developed pneumorrhachis, pneumomediastinum, pneumothorax, and surgical
emphysema in the absence of trauma. In trauma victims, these
ndings may suggest spinal fracture or hidden severe injuries.
Pneumorrhachis can be diagnosed on a radiograph or a CT scan
of the spine, with CT being preferred (4, 11).
The accumulated air may cause symptoms like mild radicular pain, neurological compression, and sequelae such as
paraplegia (9, 10, 12). Spontaneous pneumorrhachis does not
require a specic intervention, as most cases are self-limiting.
Spontaneous resorption of the air within 2 to 3 weeks commonly occurs (810). Surgical intervention can be considered
when air acts as a space-occupying lesion, causing pressure on
nervous structures and resulting in neurological decits (810).
Pneumomediastinum is a rare complication of P. jiroveci pneumonia and has been reported at the time of diagnosis, mechanical
ventilation, and trimethoprim-sulfamethoxazole treatment (11,
13, 14). In our case, we gave antimicrobial therapy for P. jiroveci
pneumonia early and adopted a conservative strategy. Our case is
unique as the patient, with previously undiagnosed HIV/AIDS,
presented with extensive pneumomediastinum, pneumorrhachis,
and subcutaneous emphysema caused by P. jiroveci pneumonia.
Although pneumomediastinum has been described in relation
with P. jiroveci pneumonia, concurrent pneumorrhachis related
to the same etiology has rarely been reported.
2.
1.
14.
190
Jung H, Lee SC, Lee DH. Kim G-J. Spontaneous pneumomediastinum with concurrent pneumorrhachis. Korean J Thorac Cardiovasc Surg
2014;47(6):569571.
3.
4.
5.
6.
7.
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11.
12.
13.
Newcomb AE, Clarke CP. Spontaneous pneumomediastinum: a benign

curiosity or a signicant problem? Chest 2005;128(5):32983302.
Carolan PL, Wright SL, Jha V. Spontaneous pneumorrhachis. Pediatr
Emerg Care 2013;29(4):508509.
Karaoglan A, Cal MA, Orki A, Arpaozu BM, Colak A. Pneumorrhachis
associated with bronchial asthma, subcutaneous emphysema and pneumomediastinum. Turk Neurosurg 2011;21(4):666668.
Manden PK, Siddiqui AH. Pneumorrhachis, pneumomediastinum,
pneumopericardium and subcutaneous emphysema as complications of
bronchial asthma. Ann Thorac Med 2009;4(3):143145.
Chassagnon G, Favelle O, Derogis V, Cottier JP. Spontaneous pneumomediastinum due to the Macklin eect: less is more. Intern Emerg Med
2015;10(6):759761
Sakai M, Murayama S, Gibo M, Akamine T, Nagata O. Frequent cause of
the Macklin eect in spontaneous pneumomediastinum: demonstration
by multidetector-row computed tomography. J Comput Assist Tomogr
2006;30(1):9294.
Okada M, Adachi H, Shibuya Y, Ishikawa S, Hamabe Y. Diagnosis and
treatment of patients with spontaneous pneumomediastinum. Respir Investig 2014;52(1):3640.
Oertel MF, Korinth MC, Reinges MH, Krings T, Terbeck S, Gilsbach
JM. Pathogenesis, diagnosis and management of pneumorrhachis. Eur
Spine J 2006;15(Suppl 5):636643.
Okoh S, Gopal KV. Pneumothorax in Pneumocystis jirovecii pneumonia: a
case report, review of clinical characteristics and management. Am J Case
Rep 2008;9 120124.
Moss S, Carey PB, Hind CR. Pneumocystis carinii pneumonia presenting
with pneumomediastinum in an HIV-positive patient. Postgrad Med J
1995;71(832):9697.
Teruya K, Yasuoka A, Yamaguchi M, Yasuoka C, Yamamoto Y, Genka I,
Tachikawa N, Kikuchi Y, Oka S. Complications during clinical courses
of Pneumocystis carinii pneumonia in patients with acquired immunodeciency syndrome. Intern Med 2001;40(3):221226.
Cho JY, Kim DM, Kwon YE, Yoon SH, Lee SI. Newly formed cystic lesions for the development of pneumomediastinum in Pneumocystis jirovecii
pneumonia. BMC Infect Dis 2009;9(1):171.
Kaji Y, Ohara G, Kagohashi K, Satoh H. Pneumomediastinum in a patient
with Pneumocystis jirovecii pneumonia. Intern Med 2012;51(16):2251.
Volume 29, Number 2
Multiple dural-based hemangiopericytomas

Edana Stroberg, DO, David H. Uhrbrock, MD, Frank Harris, MD, Subhakar Mutyala, MD, Pier Luigi DiPatre, MD, PhD, and
Ekokobe Fonkem, DO
Here we report the case of a 57-year-old man who underwent resection of

a dural-based hemangiopericytoma (HPC) in the left frontoparietal region.
The patient was treated with radiation therapy and remained symptomfree for 10 years. At 67 years of age, he presented with a mass in the
left frontal region near the same area as the first tumor, in addition to a
separate smaller mass in the right middle cranial fossa. Resection of the
larger left frontal mass revealed an HPC. Follow-up imaging 9 months
later showed a significant increase in size of the right middle cranial
fossa mass. This third mass was resected, and histological examination
also demonstrated an HPC.
emangiopericytoma (HPC) was rst described in 1942

by Stout and Murray as a highly vascularized tumor
arising from the pericytes of Zimmerman, the modied
smooth muscle cells that surround capillaries and postcapillary venules (1). In 1954, Begg and Garret rst reported a
case of an HPC occurring in the nervous system (2). These are
rare neoplasms representing 2.5% of all meningeal tumors and
0.4% of all intracranial tumors (3). The 2007 World Health
Organization (WHO) criteria developed a two-tiered system for
grading intracranial HPCs, including WHO grade II and grade
III (anaplastic) (Table 1) (4). In the largest published review of
meningeal HPC, including follow-up data on 277 patients, local
recurrence was seen in 57% of patients and systemic metastases
was seen in 27% (5). Isolated intracranial metastasis remains
an unusual event. The overall literature on intracranial HPC
remains limited, especially concerning long-term follow-up of
patients (6, 7).
CASE REPORT
A 57-year-old man without any signicant family history
or past medical history underwent resection of an extra-axial
mass in the left frontoparietal region. The pathologic diagnosis
of this rst tumor was HPC, WHO grade III. The patient was
treated with radiation therapy and remained symptom-free for
approximately 10 years.
When the patient was 67 years of age, radiologic imaging
showed an enhancing partially cystic extra-axial mass in the left
frontal region (Figures 1a and 1b). Another smaller mass was
also visualized in the right middle cranial fossa (Figure 1c). He
Table 1. 2007 World Health Organization two-tiered criteria for

intracranial hemangiopericytoma
Grade
Features
II
Monomorphous cellular spindle-cell tumor with round-tooval nuclei and intratumoral staghorn vessels
III (anaplastic)
Necrosis and/or
Mitotic activity (<5 per 10 high-power fields)
Plus at least two of the following:
Hemorrhage
Moderate to high cell density
Moderate to marked nuclear atypia
underwent resection of the larger left frontal mass, and histological examination revealed an HPC, WHO grade III. Follow-up
imaging 9 months later revealed a signicant increase in size of
the right middle cranial fossa mass (Figure 1d), which did not
appear to have obvious connection to the previous two masses.
The decision was made to proceed with resection of this third
mass due to its rapid growth rate. Histological examination
again revealed an HPC, WHO grade III. Subsequent imaging ruled out systemic metastases. At 1 year postresection, the
patient does not have any additional symptoms and continues
to be an active rancher.
The original left frontoparietal mass (the rst of the three
tumors) was highly cellular with a very rich vascular network
(Figure 2a). The vascular channels displayed a staghorn-like appearance. Multifocal necrosis and hemorrhage were identied.
The mitotic activity was up to 5 mitotic gures per 10 highpower elds. Immunohistochemical studies showed prominent
From the Department of Pathology (Stroberg, DiPatre), Department of Diagnostic

Radiology (Uhrbrock), Department of Neurosurgery (Harris, Fonkem), and
Department of Radiation Oncology (Mutyala), Baylor Scott & White Healthcare,
Temple, Texas.
Corresponding author: Ekokobe Fonkem, DO, Department of Neurosurgery,
Baylor Scott & White Healthcare, 2401 S. 31st Street, Temple, TX 76508 (e-mail:
efonkem@sw.org).
191
staining patterns were again diagnostic of

an HPC, WHO grade III.
The right middle fossa mass was
resected 9 months after the second left
frontal mass and was microscopically
similar to the previous tumors (Figures
2d and 2e). Mitotic activity was focally
brisk with up to 5 mitotic gures per 10
high-power elds. There was multifocal
coagulative necrosis (Figure 2f ). Immunohistochemistry showed tumor cells to
be diusely and strongly immunoreactive for CD34 (Figure 2g) and CD99
(Figure 2h), whereas keratin, epithelial
membrane antigen, and smooth muscle actin were negative. These ndings
were again diagnostic of an HPC, WHO
grade III.
DISCUSSION
The multifocal presentation of intracranial HPCs can have three explanations: 1) recurrence of a previously
resected HPC; 2) metastasis of an HPC
to other intracranial, dural-based locations; or 3) development of independent
HPCs at dierent sites. In the present
case, it is most likely that the second
tumor was a recurrence of the primary
tumor resected 10 years earlier since the
second HPC arose at a site very close
to the rst HPC (left frontoparietal region). The third dural-based HPC, however, developed in an entirely separate
area of the brain (in the right middle
Figure 1. Ten years after the first mass was resected, the patient presented with worsening neurological symp- fossa), relatively distant from the site of
toms. (a) An axial contrast-enhanced T1-weighted image showed a left frontal, extra-axial, avidly enhancing, the rst two HPCs. There is no specic
partially cystic tumor resulting in significant mass effect on the left frontal lobe and lateral ventricles. (b) An vascular connection favoring this paraxial T2-weighted image demonstrated the extent of vasogenic edema in the frontal lobes and genu of the
ticular spread; however, there is a poscorpus callosum. The dark signal in the cystic portion of the mass posteriorly represents dependently layering
sible, although distant, cerebrospinal
hemorrhage. (c) In addition, axial contrast-enhanced T1-weighted imaging showed a right middle cranial
fossa, extra-axial, avidly enhancing mass distant from the left frontal mass. (d) An axial contrast-enhanced T1- uid connection. It is less likely that the
weighted image acquired 9 months later showed the right middle cranial fossa mass to have increased in size. third HPC developed independently of
the rst two HPCs. In most cases of intracranial HPC with reported recurrence
and/or metastases, recurrence at the primary tumor site is usuCD34 reactivity and negative epithelial membrane antigen.
ally followed by systemic rather than intracranial metastases.
The morphology and immunostaining patterns supported a
The interesting feature of this particular case is the lack of
diagnosis of an HPC, WHO grade III.
systemic metastases in the setting of an unusual intracranial
The patients mass in the left frontal region, which was remetastasis from one dural-based location to another without
moved 10 years later, showed histopathology characteristics
an obvious connection. Since recurrence with a greater degree
similar to those of the rst tumor (Figure 2b). Reticulin staining
of malignancy can develop following an extended disease-free
highlighted the rich microvascular network (Figure 2c). As with
interval, this case highlights the importance of careful long-term
the original tumor, CD34 reactivity was diusely positive and
follow-up for patients with HPC.
epithelial membrane antigen was negative. The morphology and
192
Volume 29, Number 2
1.
2.
3.
d
4.
5.
6.
7.
Stout AP, Murray MR. Hemangiopericytoma: a vascular tumor featuring Zimmermans pericytes. Ann Surg
1942;116(1):2633.
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occurring in the meninges: case report.
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BW, Shaw EG. Meningeal hemangiopericytoma: histopathological features,
treatment, and long-term follow-up of 44
cases. Neurosurgery 1989;25(4):514522.
Giannini C, Rushing EJ, Hainfeller JA.
Haemangiopericytoma. In Louis DN,
Ohgaki H, Wiestler OD, Cavanee WK,
eds. WHO Classication of Tumours of
the Central Nervous System. Lyon: IARC,
2007:178180.
Rutkowski MJ, Sughrue ME, Kane AJ,
Aranda D, Mills SA, Barani IJ, Parsa AT.
Predictors of mortality following treatment of intracranial hemangiopericytoma. J Neurosurg 2010;113(2):333339.
Rutkowski MJ, Jian BJ, Bloch O, Chen
C, Sughrue ME, Tihan T, Barani IJ,
Berger MS, McDermott MW, Parsa AT.
Intracranial hemangiopericytoma: clinical
experience and treatment considerations
in a modern series of 40 adult patients.
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Tian R, Hao S, Hou Z, Bian L, Zhang Y,
Wu W, Xu F, Li H, Liu B. Clinical characteristics and prognostic analysis of recurrent
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system: a review of 46 cases. J Neurooncol
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Figure 2. (a) Hematoxylin and eosin (H&E)stained section of the original tumor showing a rich vascular network
with a staghorn-like appearance. (b) H&E-stained section of the second tumor removed 10 years later showing
patternless sheets of plump cells with indistinct cell borders and abundant vasculature with a staghorn-like appearance. (c) Reticulin stain of the second tumor, highlighting the rich microvascular network and pericellular reticulin
fibers. (df) H&E-stained section of the third tumor 9 months later, showing a highly cellular tumor composed of
sheets of cells in a highly vascular background with (d, e) a vaguely staghorn-like configuration and (f) multifocal
coagulative necrosis. Immunohistochemistry showed tumor cells to be diffusely and strongly immunoreactive for
(g) CD34 and (h) CD99.
April 2016
Multiple dural-based hemangiopericytomas
193
Colorectal cancer implant in an external hemorrhoidal skin tag

Lampros Liasis, MD, and Harry T. Papaconstantinou, MD
External hemorrhoidal skin tags are generally benign. Colorectal cancer

metastases to the squamous epithelium of perianal skin tags without other
evidence of disseminated disease is a very rare finding. We present the
case of a 61-year-old man with metastasis to an external hemorrhoidal
skin tag from a midrectal primary adenocarcinoma. This case report highlights the importance of close examination of the anus during surgical
planning for colorectal cancers. Abnormal findings of the perianal skin
suggesting an implant or metastatic disease warrant biopsy, as distal
spread and seeding can occur. In our patient, this finding appropriately
changed surgical management.
xternal hemorrhoidal skin tags are benign and are removed if they cause local problems (irrigation, pruritus,
etc.) or for cosmetic reasons. We describe a patient with
colon cancer where abnormal ndings in an anal skin
tag had survival signicance.
CASE REPORT
A 61-year-old man was referred to the colorectal service at
Baylor Scott & White Memorial Hospital in Temple, Texas,
complaining of anal pain and bleeding. During perianal examination, two unremarkable acutely thrombosed external
hemorrhoids were noted. Endoscopic examination of the colon
revealed a locally advanced poorly dierentiated rectal adenocarcinoma 5 to 7 cm from the anal verge. Endorectal ultrasound
revealed a uT3N0Mx tumor. Computed tomography (CT)
evaluation of the chest, abdomen, and pelvis was unremarkable for metastatic disease. The patient underwent neoadjuvant
chemotherapy and radiation therapy. Radiation therapy was
provided using CT-guided three-dimensional conformal therapy
with 50 Gy to the tumor bed and 45 Gy to the pelvic lymph
nodes. The perineal skin was spared. Two months after completing neoadjuvant therapy, the patient was reevaluated for surgical
planning. During anorectal examination, he was noted to have
asymptomatic external hemorrhoidal skin tags in the location
of the previous thrombosed hemorrhoids. These tags, however,
exhibited a hyperemic rm ulcerated mass at the tip (Figure 1a).
Biopsies of the mass on the external tag demonstrated an
invasive poorly dierentiated adenocarcinoma. Given this result, the patient underwent abdominoperineal resection of the
194
rectum. The primary cancer in the rectum was 7 cm from the

hemorrhoidal implant (Figure 1b). The hemorrhoidal tag had
normal squamous epithelium with a focus of invasive poorly differentiated adenocarcinoma (Figure 1c). There was no evidence
of lymphovascular invasion or tumor involvement of the hemorrhoidal vascular pedicle. The closest margin to the implant
was 3 cm. The patient was discharged with no complications
from surgery and underwent adjuvant chemotherapy. At 5-year
follow-up, there was no recurrence of the neoplasm.
DISCUSSION
Rectal cancer has been shown to spread distally as far as 5 cm
(1). Downstream seeding of colorectal adenocarcinoma is most
commonly identied in anastomotic sites (2, 3), biopsy sites
(4), and anal stulas (515), as well as in perianal areas with a
previous traumatic intervention (16, 17). Literature pertaining
to metastatic disease to hemorrhoids is scarce and usually focuses
on metastasis to hemorrhoidectomy sites (8, 1820). Colorectal
metastasis to hemorrhoidal sites that were treated with banding
or sclerotherapy have been reported (21). Only 3 cases have been
reported of colorectal cancer implants to hemorrhoids without
previous therapeutic intervention (22, 23). It is especially remarkable that in all 3 case reports, implants were noted during
the follow-up period after the operation for primary colorectal
adenocarcinoma. Furthermore, all implants involved the internal
hemorrhoidal plexus where adenomatous epithelium is normally
found. Our case report is the rst to describe the downstream
colorectal metastasis to an external hemorrhoidal skin tag that
was discovered after neoadjuvant therapy and before surgical
intervention. This also is the only case of downstream metastasis
aecting a nonoperated site of squamous epithelium.
In our patient, repeat examination of the anal canal prior
to the operation allowed for diagnosis of the metastasis, which
changed the surgical strategy. The patient received the optimal
From the Department of Surgery, Northwick Park Hospital, London North West
Healthcare NHS Trust, and Imperial College School of Medicine, London, UK
(Liasis); and Department of Surgery, Baylor Scott & White Memorial Hospital,
Temple, Texas (Papaconstantinou).
Corresponding author: Harry T. Papaconstantinou, MD, Glen E. and Rita K. Roney
Professor and Chairman, Department of Surgery, Baylor Scott & White Memorial
Hospital, 2401 South 31st Street, Temple, TX 76508 (e-mail: hpapaconstantinou@
sw.org).
Figure 1. (a) Abnormal external anal skin tag with hyperemic ulcerated tip (white arrow). (b) Surgical specimen after abdominoperineal resection. The black
arrow shows the site of primary adenocarcinoma of the rectum, and the white arrow shows the adenocarcinoma implant in an external hemorrhoidal skin tag.
(c) Photomicrograph of normal squamous epithelium of an anal skin tag with a focus of invasive adenocarcinoma (hematoxylin and eosin stain at 10 magnification).
abdominal-perineal resection of the rectum instead of the previously planned low anterior resection. It is important to note that
if there was evidence of the tumor implant in the hemorrhoidal
tag before neoadjuvant therapy, the eld of radiation therapy
would have included the perineal skin, inguinal lymph nodes, and
ischiorectal fossa. This would be in direct response to the pattern
of lymph node drainage exhibited in the distal rectum and anus.
1.
Scott N, Jackson P, al-Jaberi T, Dixon MF, Quirke P, Finan PJ. Total

mesorectal excision and local recurrence: a study of tumour spread in the
mesorectum distal to rectal cancer. Br J Surg 1995;82(8):10311033.
2. Basha G, Penninckx F. Exfoliated tumour cells and locally recurrent
colorectal cancer. Acta Chir Belg 1996;96(2):6670.
3. Futami R, Shimanuki K, Sugiura A, Tsuchiya Y, Kaneko M, Okawa K,
Mineta S, Sugiyama Y, Akimaru K, Tajiri T. Recurrence of colonic cancer twice at the site of stapled colorectal anastomosis. J Nippon Med Sch
2007;74(3):251256.
4. Basha G, Ectors N, Penninckx F, Filez L, Geboes K. Tumor cell implantation after colonoscopy with biopsies in a patient with rectal cancer: report
of a case. Dis Colon Rectum 1997;40(12):15081510.
5. Benjelloun B, Aitalalim S, Chbani L, Mellouki I, Mazaz K, Aittaleb K.
Rectosigmoid adenocarcinoma revealed by metastatic anal stula. The
visible part of the iceberg: a report of two cases with literature review.
World J Surg Oncol 2012;10(1):209.
6. Gomes RM, Kumar RK, Desouza A, Saklani A. Implantation metastasis
from adenocarcinoma of the sigmoid colon into a perianal stula: a case
report. Ann Gastroenterol 2014;27(3):276279.
7. Gupta R, Kay M, Birch DW. Implantation metastasis from adenocarcinoma of the colon into a stula-in-ano: a case report. Can J Surg
2005;48(2):162163.
8. Isbister WH. Unusual recurrence sites for colorectal cancer. Dig Surg
2000;17(1):8183.
9. Ishiyama S, Inoue S, Kobayashi K, Sano Y, Kushida N, Yamazaki Y, Yanaga
K. Implantation of rectal cancer in an anal stula: report of a case. Surg
Today 2006;36(8):747749.
10. Kouraklis G, Glinavou A, Kouvaraki M, Raftopoulos J, Karatzas G. Anal
lesion resulting from implantation of viable tumour cells in a pre-existing
anal stula. A case report. Acta Chir Belg 2002;102(3):212213.
April 2016
11. Rakoto-Ratsimba HN, Rakototiana AF, Rakotosamimanana J, Ranaivozanany A. Anal adenocarcinoma revealed by a stula-in-ano. Report of a
case. Ann Chir 2006;131(9):564566.
12. Rollinson PD, Dundas SA. Adenocarcinoma of sigmoid colon seeding
into pre-existing stula in ano. Br J Surg 1984;71(9):664665.
13. Schazin DM, Stahl TJ, Smith LE. Perianal mucinous adenocarcinoma: unusual case presentations and review of the literature. Am Surg
2003;69(2):166169.
14. Tomimaru Y, Ohue M, Noura S, Tanida T, Miyashiro I, Yano M, Ohigashi
H, Sasaki Y, Ishikawa O, Imaoka S. A case of anal stula cancer probably developing from intraluminal dissemination of rectal cancer. Gan To
Kagaku Ryoho 2005;32(11):17761778.
15. Wakatsuki K, Oeda Y, Isono T, Yoshioka S, Nukui Y, Yamazaki K, Nabeshima
S, Miyazaki M. Adenocarcinoma of the rectosigmoid colon seeding into
pre-existing anal stula. Hepatogastroenterology 2008;55(84):952955.
16. Mekata E, Shimizu T, Endo Y, Tani T. The rapid growth of intraluminal tumor metastases at the intestinal wall sites damaged by obstructive colitis due
to sigmoid colon cancer: report of a case. Surg Today 2008;38(9):862865.
17. Tranchart H, Benoist S, Penna C, Julie C, Rougier P, Nordlinger B. Cutaneous perianal recurrence on the site of Lone Star Retractor after J-pouch
coloanal anastomosis for rectal cancer: report of two cases. Dis Colon
Rectum 2008;51(12):18501852.
18. Abbasakoor F, Srivastava V, Swarnkar K, Stephenson BM. Implantation
anal metastases after out-patient treatment of haemorrhoids. Ann R Coll
Surg Engl 2004;86(1):3839.
19. Hsu TC, Lu IL. Implantation of adenocarcinoma on hemorrhoidectomy
wound. Int J Colorectal Dis 2007;22(11):14071408.
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2000;66(8):789792.
21. Cantos-Pallars M, Garca-Armengol J, Mulas-Fernndez C, Sancho-Moya C,
Fabra-Cabrera I, Bruna-Esteban M, Roig-Vila JV. Perianal cutaneous metastases from colorectal adenocarcinoma. Rev Esp Enferm Dig 2012;104(1):4142.
22. Gujral DM, Bhattacharyya S, Hargreaves P, Middleton GW. Metastatic
rectal adenocarcinoma within haemorrhoids: a case report. J Med Case
Reports 2008;2(1):128.
23. Scott NA, Taylor BA, Wol BG, Lieber MM. Perianal metastasis from
a sigmoid carcinomaobjective evidence of a clonal origin. Report of a
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Colorectal cancer implant in an external hemorrhoidal skin tag
195
Bilateral synchronous plasmacytoma of the testis

Geetha Narayanan, MD, DM, Rona Joseph, MD, and Lali V. Soman, MBBS
Extramedullary plasmacytoma (EMP) is usually seen in the head and neck

regions and in the upper respiratory, gastrointestinal, and central nervous
systems. Testis is a rare site for EMP, and bilateral synchronous testicular
plasmacytoma occurring as an isolated event at initial presentation has
been reported only once previously. We present herein the second such
report in a 70-year-old man who underwent bilateral orchidectomy.
lasmacytoma is a discrete solitary mass of neoplastic

monoclonal plasma cells occurring either in bone (solitary plasmacytoma of bone) or in soft tissues (extramedullary plasmacytoma, EMP). EMP represents 3%
to 5% of all plasma cell neoplasms. The common sites of EMP
are the head and neck, upper respiratory system, gastrointestinal system, and central nervous system (1). Testis is a rare site
for EMP, and EMP accounts for only 0.03% to 0.15% of all
testicular tumors (24). Testicular plasmacytoma usually occurs
as part of multiple myeloma or as a site of recurrence. Rarely,
isolated testicular plasmacytomas occur as a presenting feature,
with a few cases reported (57). Even more rare is bilateral
and synchronous testicular plasmacytoma, with only four cases
reported in the literature, and in only one case it occurred as
an isolated event at the initial presentation (811). We present
the second report of isolated bilateral synchronous testicular
plasmacytoma as the presenting feature in a 70-year-old man.
CASE REPORT
A 70-year-old man was evaluated for pain and swelling of
the right testis of 6 months duration. Right inguinal hernia
and bilateral hydrocele were initially diagnosed. He underwent
right hernioplasty and hydrocelectomy and eversion of the left
tunica vaginalis sac. Swelling recurred after 4 months. Doppler
ultrasound of the testis showed a grossly enlarged right testis (76
43 67 mm) with multiple hypoechoic lesions, lobulations,
and increased vascularity. He underwent right orchidectomy,
and the testis showed a circumscribed grayish-white lobulated
lesion, 7.5 6 cm, with no normal testicular tissue seen. The
section showed immature and atypical plasma cells in sheets
inltrating the interstitial tissue and surrounding the atrophic
tubules (Figure 1a). On immunohistochemistry, the cells were
positive for CD138 and kappa light chain staining (Figure 1b)
196
and negative for CD20 and CD5 and lambda, suggestive of

plasmacytoma. Two months later, the patient noticed swelling
of his left testis. Ultrasound showed similar hypoechoic lesions,
and he underwent left orchidectomy.
The patients hemoglobin level was 13.1 g/dL; total white
blood cell count, 10,200/mm3; and platelet count, 2.88 lakhs/
mm3; his total protein and renal function were normal. His
serum IgG was 1838 mg/dL; IgA, 212 mg/dL; IgM, 86 mg/
dL; free kappa light chain, 33.5 mg/dL; and free lambda, 36.7
mg/dL. Serum electrophoresis and serum immunoxation did
not show any abnormal bands. His bone marrow aspiration
was normal, and there were no lytic lesions on skeletal survey.
DISCUSSION
EMP occurs in 18% of patients with multiple myeloma
(12). Testicular involvement by plasmacytoma is rare but well
documented, and most patients have myeloma at the time of
diagnosis or develop plasmacytoma during relapse (4, 1316).
EMP occurs rarely as a solitary plasmacytoma at initial presentation in the absence of systemic myeloma (2, 46, 14, 15, 17).
Anghel et al reported 52 cases of testicular plasmacytoma, and
most had prior or concurrent multiple myeloma (4).
Synchronous cancers are dened as malignant tumors that
present simultaneously or within a 6-month period of identication of the original tumor. Bilateral involvement of testes by
plasmacytoma is unusual, and most cases have occurred asynchronously at the time of relapse. Two cases of myeloma in
remission relapsing later with bilateral testicular plasmacytoma
were reported (9, 10). A 43-year-old man with myeloma was
detected to have both testes involved by a positron emission
tomography/computed tomography scan done prior to allogeneic transplantation (11). However, there has been only one
previous report of bilateral synchronous testicular plasmacytoma presenting without evidence of myeloma occurring in a
48-year-old man (8). Our patient also presented initially with
From the Department of Medical Oncology, Regional Cancer Centre, Trivandrum,

India.
Corresponding author: Geetha Narayanan, MD, DM, Professor and Head,
Department of Medical Oncology, Regional Cancer Centre, Trivandrum 695011,
Kerala, India (e-mail: geenarayanan@yahoo.com).
Figure 1. Orchidectomy section showing (a) sheets of plasma cells infiltrating interstitial tissue (hematoxylin and eosin, 100) and (b) immunopositivity for CD138
(100).
isolated bilateral testicular plasmacytoma and did not have any

evidence of myeloma.
The mean age at diagnosis of testicular plasmacytoma is 55
to 60 years old (5). Patients usually present with a rm testicular
mass which may be tender. Sonographic imaging has shown the
masses to be either homogeneous or heterogeneous and typically
hypoechoic. Hypervascularity on color ow and power Doppler
imaging is a consistent nding in testicular plasmacytomas (6,
13). On microscopy, the tumor shows sheets of plasma cells with
varying degrees of dierentiation. The diagnosis is conrmed
by immunostaining with CD138, CD79a, and light chain restriction (5). Our patient also showed positivity for CD138.
Testicular plasmacytomas have a higher incidence of IgA than
multiple myelomas (15, 18). The diagnosis of isolated testicular
plasmacytoma requires studies to exclude systemic myeloma.
Testicular plasmacytoma, like other primary testicular tumors, requires radical inguinal orchidectomy. Local radiation
may be considered in patients with incomplete resection or
recurrent or refractory disease (5). The overall prognosis for
patients with testicular plasmacytoma is poor, with a high rate
of progression to multiple myeloma (14). Hence, these patients
require close monitoring. The survival of patients with multiple
myeloma has improved over the years as a result of better understanding of the disease biology and advancement in targeted
treatment modalities.
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Pow Sang M, Astigueta JC, Abad M, Snchez J, Len J. Testicular plasmacytoma as presentation of multiple myeloma: case report and review
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Anghel G, Petti N, Remotti D, Ruscio C, Blandino F, Majolino I. Testicular plasmacytoma: report of a case and review of the literature. Am J
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April 2016
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Bilateral synchronous plasmacytoma of the testis
197
Presentation of epidermolytic acanthomas as multiple tan

papules on the vulva
J. Wesley Fletcher, MD, Arathi Ramamurthi, BA, and Palak Parekh, MD
Epidermolytic hyperkeratosis is a histological reaction pattern seen in a

variety of disease processes, including epidermolytic ichthyosis, Vorners
epidermolytic palmoplantar keratoderma, epidermal nevus, and solitary
epidermolytic acanthoma. Here we present the case of a 59-year-old
woman with multiple asymptomatic papules on her vulva. Clinical differential diagnoses included condyloma acuminata, seborrheic keratoses, bowenoid papulosis, adnexal tumors, and papular acantholytic
dyskeratosis. Shave biopsy revealed findings consistent with epidermolytic hyperkeratosis. This case represents an interesting presentation of
focally disseminated vulvar epidermolytic acanthomas and highlights the
importance of a biopsy in establishing this diagnosis.
pidermolytic hyperkeratosis (EHK) is a histological reaction pattern that may be seen in several clinical settings,
including epidermolytic ichthyosis (EI), Vorners epidermolytic palmoplantar keratoderma (PPK), epidermal
nevus (especially systematized variant), solitary epidermolytic
acanthomas, and as an incidental nding. Solitary epidermolytic acanthomas may have a nonspecic presentation, making
clinical diagnosis rather dicult (1, 2). Here, we present an
unusual case of multiple vulvar epidermolytic acanthomas and
the attendant diagnostic challenge.
CASE REPORT
A 59-year-old white woman presented with multiple asymptomatic papules on her vulva which she had noticed several
months earlier while bathing. She denied lesions elsewhere.
Previously, she had hypertension and hypercholesterolemia, and
her father had melanoma. She had no history of skin cancer.
She had been married to the same male partner for >10 years.
After noticing one papule, she began discovering other small
papules in her genital region and became concerned. These lesions never itched, bled, or bothered her. She had no fever, chills,
or weight loss. A 4 mm verrucous papule was noted on the left
labium majus surrounded by smaller 1 to 2 mm hyperkeratotic
papules on both the left and right labia (Figure 1). The patient
had no regional lymphadenopathy or similar lesions elsewhere.
Shave biopsy of a lesion on the left labium majus revealed
papillomatosis with hyperkeratosis, hypergranulosis with
clumped keratohyaline granules, and multifocal vacuolization
198
Figure 1. A 3 mm hyperkeratotic papule located on the left labia majora surrounded by smaller 1 to 2 mm hyperkeratotic papules on both the left and right
labia majora.
of suprabasilar keratinocytes consistent with epidermolytic hyperkeratosis (Figure 2). The patient was relieved to learn that her
lesions did not represent a sexually transmitted disease and were
consistent with agminated epidermolytic acanthomas.
DISCUSSION
EHK is a histological nding seen in several conditions,
including EI. EI is a genodermatosis characterized by blistering
and erythroderma at birth or shortly thereafter with hyperkeratosis most pronounced on extensor surfaces later in life.
Although this disorder usually displays an autosomal dominant
inheritance pattern, 50% of cases result from spontaneous mutations (3). This form of ichthyosis is characterized by a defect of
suprabasal keratinocytes due to mutations in keratins 1 and 10
and has a prevalence of approximately 1 in 200,000 to 300,000
individuals. Histologically, EHK may also be seen in Vorners
PPK, an autosomal dominant dermatosis, which presents early
in life with thickening of the skin on the palms and soles due
to mutations in keratins 1 and 9. Children of patients with EI
From Texas A&M Health Science Center College of Medicine, Temple, Texas
(Fletcher, Ramamurthi, Parekh) and Department of Dermatology, Baylor Scott &
White, Temple, Texas (Fletcher, Parekh).
Corresponding author: Arathi Ramamurthi, BA, 3009 Ira Young Drive, Apt. 1306,
Temple, TX 76504 (e-mail: ramamurthi@medicine.tamhsc.edu).
Figure 2. (a) Lower-power view demonstrating hyperkeratosis, papillomatosis, clumped keratohyalin granules, and superficial epidermal vacuolization consistent
with epidermolytic hyperkeratosis (hematoxylin and eosin, 10). (b) Higher magnification revealing clumped keratohyalin granules and multifocal vacuolization of the
superficial epidermis (hematoxylin and eosin, 40).
as well as those with mosaic presentations (such as epidermal

nevus) with germline mutations may harbor the mutation and
manifest EI.
Our patient presented with grouped vulvar epidermolytic
acanthomas. We hypothesize that her presentation may represent genetic mosaicism with a delayed onset; however, she
did not undergo formal genetic testing. She denied any family
history in her parents or children of any skin diseases and, in
particular, denied any known diagnoses of EI, Vorners PPK,
and epidermal nevi in her rst-degree family members.
Solitary epidermolytic acanthomas have been described in
widespread locations including the face, extremities, and genitalia (4). Epidermolytic acanthomas localized to the genital area
were once noted to be rare, with fewer than 10 cases reported;
however, recent studies suggest that this location is more common than previously thought (57). The genitalia may in fact be
the most common anatomic site for epidermolytic acanthomas
(5). Clinically, epidermolytic acanthomas may present as sessile,
esh-colored, or brown papules, as well as exophytic verrucous
papules (5). A nonspecic clinical presentation can make diagnosis challenging. Kazlouskaya et al retrospectively reviewed
64 biopsies from 60 patients and found that not a single case
of EHK was diagnosed correctly on initial clinical presentation.
Frequent misdiagnoses included warts, seborrheic keratoses,
condylomas, molluscum, and squamous cell carcinoma (5).
The clinical dierential diagnoses of epidermolytic acanthomas of the genital area include viral and neoplastic entities.
Patients are often concerned about sexually transmitted diseases
(7). In situ hybridization studies of genital epidermolytic acanthomas have failed to show any evidence of genital human papillomavirus types in these lesions (5). Diagnosis of epidermolytic
April 2016
acanthoma requires histopathological examination. Biopsy of a

single lesion in our patients case was diagnostic.
Treatment of epidermolytic acanthomas is not necessary
given their benign nature. If desired, lesions may be treated with
surgical excision or cryotherapy. One report noted complete
resolution with topical 5% imiquimod cream after 4 weeks
of use (8). Our patient noted softening of the lesions with decreased roughness with use of a topical lactic acid preparation;
this has not been previously reported in the literature. Other
topical therapies that can be used include glycerin, urea, and
alpha-hydroxy acids, which may improve the hyperkeratotic,
scaly nature of EHK (3).
1.
2.
3.
4.
5.
6.
7.
8.
Banky JP, Turner RJ, Hollowood K. Multiple scrotal epidermolytic acanthomas; secondary to trauma? Clin Exp Dermatol 2004;29(5):489491.
Yang JH, Kim JK, Won CH, Chang SE, Lee MW, Choi JH, Moon KC.
Isolated epidermolytic acanthoma in a renal transplant recipient. Ann
Dermatol 2011;23(3):415416.
Kwak J, Maverakis E. Epidermolytic hyperkeratosis. Dermatol Online J
2006;12(5):6.
Abbas O, Wieland CN, Goldberg LJ. Solitary epidermolytic acanthoma: a clinical and histopathological study. J Eur Acad Dermatol Venereol
2011;25(2):175180.
Kazlouskaya V, Lambe J, Elston D. Solitary epidermolytic acanthoma.
J Cutan Pathol 2013;40(8):701707.
High WA, Miller MD. Localized epidermolytic hyperkeratosis of the
female genitalia: a case report and review of an underappreciated disorder
of women. MedGenMed 2005;7(4):33.
Bogale SR, Chan CS, McIntire H, Hsu S. Epidermolytic acanthoma of the
scrotum: A rare mimicker of condyloma acuminatum. Dermatol Online J
2011;17(1):6.
Jang BS, Jang HS, Park HJ, Kim MB, Oh CK, Kwon KS. Multiple scrotal
epidermolytic acanthomas successfully treated with topical imiquimod.
J Dermatol 2007;34(4):267269.
Presentation of epidermolytic acanthomas as multiple tan papules on the vulva
199
Rumpel-Leede phenomenon presenting as a

hypertensive urgency
Daniel Varela, MS-4, Dat Tran, MS-4, Kyari Sumayin Ngamdu, MD, Brett Trullender, MD, Debabrata Mukherjee, MD, MS,
and Aamer Abbas, MD
Rumpel-Leede (R-L) phenomenon is the rare event in which the small

dermal capillaries of an extremity rupture in response to application of a
compressive device to that extremity, such as when inflating a cuff during
noninvasive blood pressure monitoring or when applying a tourniquet to
draw blood. This capillary rupture results in formation of a petechial rash
distal to the compressive device. R-L phenomenon is believed to occur
most often in patients with underlying vascular disease, such as diabetes
mellitus or thrombocytopenia. R-L phenomenon is most often benign,
though it may rarely be associated with pain and discomfort. There is no
treatment for this condition apart from treatment of the underlying vascular disease or thrombocytopenia. We report a 57-year-old woman who
presented with hypertensive urgency and experienced R-L phenomenon
during blood pressure cuff inflation.
he Rumpel-Leede (R-L) phenomenon was described in

1909 by Dr. Theodor Rumpel and again in 1911 by
Dr. Carl Stockbridge Leede while treating patients with
scarlet fever (1), where R-L phenomenon occurred following application of a tourniquet. Currently, most cases of R-L
phenomenon are reported in elderly patients with a history of
diabetes and hypertension, or in patients with thrombocytopenia. We present a case of R-L phenomenon in a nondiabetic
patient with a history of uncontrolled hypertension.
CASE PRESENTATION
A 57-year-old nondiabetic woman with a 10-year history of
systemic hypertension and medication nonadherence presented
with severe right-sided facial pain radiating to the occiput and
neck and associated numbness and tingling aecting the right
side of her face, right arm, and right leg. Noninvasive blood
pressure (BP) monitoring revealed a BP of 272/124 mm Hg.
While the patients BP was being recorded, she began to complain of sharp pain in her left upper arm, where the BP cu
had been placed. She subsequently developed an erythematous
petechial rash spreading distally from her left elbow down to
her ngers, and when the cu was removed, striae were observed along the full circumference of her upper arm (Figure 1).
After the cu was removed, the patients arm pain rapidly resolved, but the petechial rash and striae persisted. The patient
reported that this phenomenon had occurred several times in the
200
past during BP monitoring, with the initial episode occurring

10 years earlier, when hypertension was rst diagnosed.
The patients workup included a normal white blood cell
count (9.78 109/L) and platelet count (317 109/L). Her
serum chemistries, electrocardiogram, echocardiogram, head
computed tomography (CT), magnetic resonance imaging,
and magnetic resonance angiography were also normal. A CT
of the patients face revealed a right periodontal abscess with
mandibular cellulitis. The cellulitis was successfully treated with
antibiotics, and the petechial rash had resolved by the time the
patient returned to the clinic 1 month after discharge from the
hospital.
DISCUSSION
The formation of petechiae distal to the BP cu during BP
monitoring is quite common, particularly in diabetic patients
(2). These petechiae may be mild and often go undetected. R-L
phenomenon is a more severe form of petechial hemorrhage,
resulting in an apparent erythematous rash, which is much
less common and is seen almost exclusively in patients with
thrombocytopenia or an underlying vascular disease, most often diabetes. The present case is remarkable for the absence of
either of these ndings. Only 2 other cases of R-L phenomenon
have been reported in patients without thrombocytopenia or
vascular disease: the rst was a 72-year-old woman, where the
presence of R-L phenomenon was attributed to age-related
capillary fragility (3); the second case was believed to have
resulted from the use of a BP cu that was too small for the
patients arm (1). In the present case, R-L phenomenon was
likely related to the patients state of hypertensive urgency, with
a BP of 272/124 mm Hg. We believe that the BP cu ination
in the presence of signicant venous pressure resulted in the
rupture of dermal capillaries, even in the absence of underlying
capillary fragility.
From Texas Tech University Health Sciences Center Paul L. Foster School of
Medicine, El Paso, Texas (Varela, Tran, Ngamdu, Trullender, Mukherjee, Abbas);
and the Departments of Internal Medicine (Ngamdu, Mukherjee, Abbas),
Emergency Medicine (Trullender), and Cardiology (Mukherjee, Abbas), University
Medical Center, El Paso, Texas.
Corresponding author: Daniel Varela, 6857 Granero Drive, El Paso, TX 79912
(e-mail: daniel.varela@ttuhsc.edu).
Another unique nding in

this case is that our patient complained of pain in her arm during
BP monitoring, an uncommon
finding in R-L phenomenon.
Most reported cases of R-L
phenomenon resolved within 2
weeks. While our patients most
recent episode resolved within 1
month, she did report that previous episodes persisted for up to
3 months.
1. Wang K, Lee J. Images in clinical

medicine. Rumpel-Leede sign. N
Engl J Med 2014;370(1):e1.
2. Eichner HL. Rumpel-Leede sign associated with a noninvasive ambulatory blood pressure monitor. JAMA
1985;254(4):506.
3. Rehman HU, Kambo J. RumpelLeede phenomenon: a case report.
Can J Gen Intern Med 2014;9(4):159.
Figure 1. Views of the patient's left arm and hand, showing (a) striae along the upper arm (black arrow), followed by
transition to an erythematous petechial rash distal to the elbow; (b) the demarcation between the rash and the patient's
normal skin tone (red arrow); and (c) the most prominent part of the rash over the dorsal surface of the patient's wrist
and hand.
April 2016
Rumpel-Leede phenomenon presenting as a hypertensive urgency
201
Arm pain and erythema

Brandon M. Barth, MD, and Andrew L. Juergens, MD
Pyomyositis can be a difficult

diagnosis to make, as it can
mimic many other disease processes. Various laboratory studies
can be abnormal with pyomyositis, but none are specific to the
disease. Early disease can generally be treated with antibiotics
alone, whereas advanced disease
frequently requires emergent surgical intervention with significant
resuscitation. We describe a case
of pyomyositis of the right arm.
yomyositis is an infection of skeletal muscle

that arises from a hematogenous source. Figure 1. (a) The right arm and shoulder demonstrate significant erythema and swelling. (b) Coronal computed tomography
Staphylococcus aureus is the demonstrates multiple fluid-filled collections (arrows).
most common pathogen (1,
2). Other organisms include Streptococcus pyogenes, Escherichia
systemic symptoms such as fevers and denied involvement of
coli, and mycobacteria (1, 3). This infection is associated with
other joints. Examination revealed an exquisitely tender right
immunosuppression, intravenous drug use, and trauma (1, 2,
shoulder and proximal arm with erythema and induration
4, 5). Large muscle bodies such as the quadriceps are most
(Figure 1a). Shoulder range of motion was limited secondary
commonly aected (6). We present a patient with pyomyositis
to patient discomfort. His erythrocyte sedimentation rate was
that was initially presumed to be thrombophlebitis.
95 mm/h, and C-reactive protein was 257 mg/L. Laboratory
studies were otherwise normal, including a white blood cell
CASE REPORT
count of 7.9 109/L.
A 53-year-old man returned to the emergency department
Computed tomography of the shoulder revealed multiple
with worsening redness, swelling, and pain of the proximal
intramuscular abscesses within the body of the biceps brachii
right arm. His similar presentation 5 days earlier was conconsistent with pyomyositis (Figure 1b). Antibiotics were started
cerning for deep venous thrombosis. He had no history of
immediately. The orthopedic surgery team took the patient to
similar symptoms prior to that episode but had a 30-packthe operating room for incision and drainage. Wound cultures
year smoking history. He took no medication and denied a
grew methicillin-sensitive Staphylococcus aureus. The patients
history of drug abuse. Diagnostic workup at that time was
positive only for a mildly elevated white blood cell count
From the Department of Emergency Medicine, Scott & White Healthcare, Temple,
of 11.9 109/L, but after a negative ultrasound the patient
Texas.
was discharged home on cephalexin for presumed supercial
Corresponding author: Brandon M. Barth, MD, Department of Emergency
thrombophlebitis. On return to the emergency department,
Medicine, Scott & White Healthcare, MS-11-AG062, 2401 S. 31st Street, Temple,
TX 76508 (e-mail: Brandon.Barth@BSWHealth.org).
the patient was afebrile and vital signs were normal. He denied
202
condition improved after the procedure, and he was discharged

home on cephalexin several days later.
DISCUSSION
The clinical course of pyomyositis is typically progressive
and can be divided into three stages as described by Chiedozi
(1). Stage 1 is limited to localized symptoms with induration
and tenderness and occasional leukocytosis. Stage 2 presents
with fevers, tenderness and edema at the site, and distinct abscess. Leukocytosis is nearly always present, and inammatory
markers are typically elevated. Stage 3 presents with systemic
infection such as endocarditis, septic arthritis, or brain abscess.
These patients often present in septic shock.
Diagnosis of pyomyositis can be dicult due to the various
disease processes it can mimic, and multiple visits to a healthcare
provider may be required before the diagnosis is reached. The
astute clinician must have a broad dierential, ranging from a
simple muscle strain to necrotizing fasciitis or septic arthritis.
Deep tissue abscess can be dicult to detect on physical exam.
Laboratory measurements such as white blood cell count lack
the sensitivity to predict disease. Patients who return for further
evaluation after receiving a presumptive diagnosis require special
consideration, particularly if their clinical course has worsened.
The diagnosis is typically made with imaging. Magnetic
resonance imaging is the most sensitive and specic study, particularly in the early stages of disease, although computed to-
April 2016
mography is very good at detecting uid collection and muscle

swelling (5). Ultrasound can also be helpful, primarily in the
second stage of disease with abscess formation and for repeat
imaging and real-time visualization (3, 7).
Treatment should begin with prompt administration of
antibiotics, which are often sucient for patients with stage 1
disease (1). Once uid collections form, antibiotics are no longer
adequate and drainage is required. In Stage 3 disease, resuscitation with vasopressor use and emergent surgical intervention
are frequently required.
Chiedozi LC. Pyomyositis. Review of 205 cases in 112 patients. Am J
Surg 1979;137(2):255259.
2. Koutures CG, Savoia M, Pedowitz RA. Staphylococcus aureus thigh
pyomyositis in a collegiate swimmer. Clin J Sport Med 2000;10(4):297
299.
3. Chu CK, Yang TL, Tan CT. Tuberculous pyomyositis of the temporal
muscle in a nonimmunocompromised woman: diagnosis by sonography.
J Laryngol Otol 2004;118(1):5961.
4. Crum NF. Bacterial pyomyositis in the United States. Am J Med
2004;117(6):420428.
5. Belsky DS, Teates CD, Hartman ML. Case report: diabetes mellitus as
a predisposing factor in the development of pyomyositis. Am J Med Sci
1994;308(4):251254.
6. Theodorou SJ, Theodorou DJ, Resnick D. MR imaging ndings of pyogenic bacterial myositis (pyomyositis) in patients with local muscle trauma:
illustrative cases. Emerg Radiol 2007;14(2):8996.
7. Quillin SP, McAlister WH. Rapidly progressive pyomyositis. Diagnosis
by repeat sonography. J Ultrasound Med 1991;10(3):181184.
1.
Arm pain and erythema
203
Rheumatoid meningitis associated with infliximab

Susan Seago, MD, Edana Stroberg, DO, and Austin Metting, MD
We present a patient who had rheumatoid meningitis while on infliximab,

a tumor necrosis factor alpha (TNF-) inhibitor, which initially presented
as transient ischemic attacks. Although our patient had been stable on
infliximab for several years, her neurologic symptoms improved when
her infliximab was held due to active infection and then recurred after
reinitiation of therapy. Rheumatoid meningitis is exceedingly rare; however, there have been several other reports of rheumatoid meningitis
developing in patients on TNF- inhibitor therapy.
heumatoid meningitis is an exceedingly rare manifestation of rheumatoid arthritis (1). Though it is uncommon, there are several case reports of rheumatoid
meningitis developing in patients on tumor necrosis
alpha (TNF-) inhibitor therapy (25). Our case is unique in
that our patients neurologic symptoms improved when iniximab, a TNF- inhibitor, was held due to active infection and
resumed following reinitiation of therapy.
CASE DESCRIPTION
A 66-year-old woman with hypertension, coronary artery
disease, gastroesophageal reux, and rheumatoid arthritis on
iniximab for 12 years developed acute-onset expressive aphasia
in late January 2014. The episode reportedly lasted around 30
minutes and resolved without intervention. She presented to
her local emergency department at that time and was diagnosed
with a transient ischemic attack after a noncontrast computed
tomography scan of the head was negative. Three days later, she
had another episode of expressive aphasia and was again diagnosed with a transient ischemic attack. Following her second
episode, ultrasound disclosed left carotid stenosis prompting a
left carotid endarterectomy.
She also developed a right corneal abrasion which developed
into dendritic keratitis followed by infections with Staphylococcus epidermidis and yeast. The iniximab was discontinued
in February 2014 prior to having a deceased-donor corneal
transplant in April 2014. Following her carotid endarterectomy
and corneal transplant, her neurologic symptoms and right eye
infection appeared to resolve, and she was started on iniximab
and methotrexate in June 2014. After resuming iniximab, she
noted intermittent episodes of lower-extremity numbness and
204
tingling. Several months later, she developed a third episode of

expressive aphasia, prompting hospitalization. On admission,
her iniximab was held and magnetic resonance imaging (MRI)
of the brain illustrated abnormal T2/FLAIR signal intensity
in her bilateral frontal lobes and anterior temporal lobe with
leptomeningeal enhancement (Figure 1). Notably, she was not
taking nonsteroidal antiinammatory medications or oral steroids prior to admission. A lumbar puncture illustrated 213
white blood cells, 86% lymphocytes, protein 85.9 g/dL, and
glucose 41 mg/dL. She was started on empiric acyclovir for
herpes simplex encephalitis.
Her clinical status continued to decline, and she developed
headache, nausea, vomiting, altered mental status, urinary incontinence, and intermittent bilateral lower-extremity numbness and paralysis over the next several days. Herpes simplex
polymerase chain reaction from her cerebrospinal uid (CSF)
was negative, and a repeat MRI of the brain illustrated interval
worsening of her abnormal T2/FLAIR signal intensity.
An electroencephalogram illustrated rare sharp waves over
the left temporal region consistent with focal seizure disorder, and she was loaded on levetiracetam. Serologic studies
illustrated a positive antinuclear antibody, rheumatoid factor,
and anti-citrullinated protein antibody with negative doublestranded DNA antibody and normal serum complement levels. Repeat lumbar puncture again illustrated a lymphocytic
pleocytosis, with 216 white blood cells, 87% lymphocytes,
protein 44 g/dL, and glucose 63 mg/dL. An extensive infectious, neoplastic, and autoimmune analysis of her CSF was
unremarkable apart from an elevated rheumatoid factor. Brain
biopsy of the dura and cerebral cortex illustrated abundant
T lymphocytes and macrophages, with a small number of B
lymphocytes and IgG4-positive cells consistent with hypertrophic pachymeningitis (Figure 2). She was treated with 1000 mg
intravenous methylprednisolone daily for 6 days with rapid
improvement of her neurologic symptoms. She ultimately
made a full neurologic recovery and was discharged on 50 mg
prednisone daily.
From Baylor Scott & White Health, Temple, Texas.

Corresponding author: Susan Seago, MD, Baylor Scott & White Health, 2401
S. 31st Street, Temple, TX 76508 (e-mail: sseago@sw.org).
Figure 1. MRI of the brain with gadolinium T2/FLAIR. (a) Sagittal image illustrating enhancement of the leptomeninges and frontal lobe. (b) Coronal image illustrating
abnormal enhancement.
DISCUSSION
Although rheumatoid meningitis is rare, the number of
biopsy-conrmed cases has increased greatly over the past several
decades, due in part to improvements in imaging and increased
access to MRI (6). The central nervous system manifestations

of rheumatoid arthritis include vasculitis, rheumatoid nodules,
and aseptic meningitis, most commonly in the form of lepto
and pachymeningitis (2). Hypertrophic pachymeningitis results
Figure 2. Brain biopsy findings suggesting a diagnosis of hypertrophic pachymeningitis. (a) Hematoxylin and eosin stain showing edematous cortex with attached
chronically inflamed fibrous dura mater. (b) CD20 stain demonstrating scattered B lymphocytes. (c) CD68 stain demonstrating an abundance of macrophages.
(d) Trichrome stain highlighting blue-staining dense fibrosis. Stains for organisms were negative, and IgG4 highlighted rare cells.
April 2016
Rheumatoid meningitis associated with infliximab
205
from chronic inammation of the dura and has been illustrated

on brain biopsy and MRI in patients with conrmed rheumatoid meningitis (3). Elevated CSF rheumatoid factor has been
proven to be a highly specic marker of rheumatologic central
nervous system disease (1). Our patients negative infectious
workup, elevated CSF rheumatoid factor, and brain biopsy illustrating hypertrophic pachymeningitis are all consistent with a
diagnosis of rheumatoid meningitis. Although previous studies
reported rheumatoid meningitis mortality rates as high as 70%
(1), more recent case reports illustrate signicant neurologic
recovery following initiation of high-dose steroids, as seen in
our patient (37).
Multiple studies illustrate a correlation between TNF-
inhibitors and both central and peripheral neuropathies. A
double-blind clinical trial using lenercept, a soluble dimeric p55
TNF-IgG fusion protein, illustrated a statistically signicant
increase in episodes of multiple sclerosis compared with placebo
(8). Another prospective study illustrated decreased conduction
velocity on electromyography after 12 months of iniximab
therapy (9). Several case reports illustrate the development of
biopsy-conrmed aseptic, autoimmune meningitis soon after
the initiation of TNF- inhibitors (24). Of these reports, one
case study illustrated the recurrence of neurologic symptoms
upon repeated administration of adalimumab and complete
resolution of symptoms following its withdrawal (5). A recent
retrospective analysis also illustrated an increased incidence of
aseptic meningitis in patients on TNF- inhibitors compared
to alternative disease-modifying antirheumatic drugs (7).
With the current trend towards early and long-term treatment with immunomodulating agents, over 2 million patients
have been treated with TNF- inhibitors worldwide. A recent
pharmacologic review found 772 reports of neurologic side
eects attributed to TNF- inhibitors submitted to the US
Food and Drug Administration between 2000 and 2009 (10).
206
While the complete neurologic eects of TNF- inhibitors

are still unknown, our case report highlights a unique clinical
presentation and encourages physicians to carefully consider
autoimmune etiologies for neurologic symptoms in patients on
TNF- inhibitor therapy and promptly discontinue treatment
when needed.
1.
Kato T, Hoshi K, Sekijima Y, Matsuda M, Hashimoto T, Otani M, Suzuki

A, Ikeda S. Rheumatoid meningitis: an autopsy report and review of the
literature. Clin Rheumatol 2003;22(6):475480.
2. Huys AC, Guerne PA, Horvath J. Rheumatoid meningitis occurring
during adalimumab and methotrexate treatment. Joint Bone Spine
2012;79(1):9092.
3. Ahmed M, Luggen M, Herman JH, Weiss KL, Decourten-Myers G, Quinlan JG, Khanna D. Hypertrophic pachymeningitis in rheumatoid arthritis
after adalimumab administration. J Rheumatol 2006;33(11):23442346.
4. Booker MJ, Flint J, Saravana S. Aseptic meningitis in a patient taking
etanercept for rheumatoid arthritis: a case report. Cases J 2008;1(1):364
365.
5. Jazeron A, Lallier JC, Rihn B, Thiercelin MC. Aseptic meningitis possibly
induced by adalimumab. Joint Bone Spine 2010;77(6):618619.
6. Hayashi Y, Namekawa M, Ohtani K, Watanabe E, Nakano I. Parkinsonism as an initial manifestation of rheumatoid meningitis. Neurol Sci
2014;35(7):11391141.
7. Cavazzana I, Taraborelli M, Fredi M, Tincani A, Franceschini F. Aseptic
meningitis occurring during anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 2014;32(5):732
734.
8. The Lenercept Multiple Sclerosis Study Group and The University of
British Columbia MS/MRI Analysis Group. TNF neutralization in MS:
results of a randomized, placebo-controlled multicenter study. Neurology
1999;53(3):457465.
9. Kotyla PJ, Sliwinska-Kotyla B, Kucharz EJ. Treatment with iniximab may
contribute to the development of peripheral neuropathy among the patients with rheumatoid arthritis. Clin Rheumatol 2007;26(9):15951596.
10. Deepak P, Stobaugh DJ, Sherid M, Sifuentes H, Ehrenpreis ED. Neurological events with tumour necrosis factor alpha inhibitors reported to the
Food and Drug Administration Adverse Event Reporting System. Aliment
Pharmacol Ther 2013;38(4):388396.
Volume 29, Number 2
Cryptococcal meningitis in a patient with sarcoidosis

Traci N. Adams, MD, and Maeghan Gibson, MD
Sarcoidosis is a multisystem granulomatous disease characterized by

the presence of noncaseating granulomas. Case reports have previously
described an association between sarcoidosis and cryptococcal infection,
but many of these patients were receiving immunosuppression at the
time of diagnosis or had limited cutaneous disease. We report a case of
cryptococcal meningitis in a 65-year-old man with a new presentation
of sarcoidosis who was not receiving immunosuppressive medications.
arcoidosis has been described as an immune paradox in

which patients demonstrate both exaggerated inammation and peripheral anergy as demonstrated by reduced
delayed-type hypersensitivity to tuberculin skin testing
and increased susceptibility to infection (13). We present a
case that is unique in that it describes the development of cryptococcal meningitis in a patient with sarcoidosis who was not
on immunosuppressive therapy and did not have extrathoracic
manifestations of the disease.
CASE PRESENTATION
A previously healthy 65-year-old man presented with
chronic cough. He had been in his usual state of health until
1 year earlier when he visited his primary care physician for a
nonproductive cough. He denied any history of gastroesophageal reux, nasal congestion, wheezing, coughing while eating,
orthopnea, hemoptysis, or dyspnea on exertion. He also denied
tobacco or drug use, recent travel, sick contacts, and bird or
mold exposure. His only medications were acetaminophen and
ibuprofen for back pain and simvastatin for hyperlipidemia.
His chest radiograph was reportedly unremarkable, and he was
treated with azithromycin and levooxacin but did not improve.
He was then evaluated at an outside hospital, where computed tomography (CT) of his chest revealed a spiculated left
lower lobe nodule measuring 2.5 1.6 cm; left supraclavicular, mediastinal, and hilar adenopathy; and extensive peribronchovascular nodularity with a perihilar distribution (Figure 1).
Bronchoscopy with bronchoalveolar lavage, bronchial brushings,
transbronchial biopsies of the right upper lobe, and biopsies
of the subcarinal lymph nodes were performed. Cytology of
the bronchial brushing was negative for malignancy, and bronchoalveolar lavage uid was negative for malignant cells and
cytomegalovirus. Transbronchial biopsies revealed focal chronic

bronchiolitis, and lymph node biopsy was benign.
One month later he presented to a neurologist with headache, dysarthria, and left hand numbness. His temperature
was 98.5F; heart rate, 89 beats per minute; blood pressure,
138/88 mm Hg; and oxygen saturation, 96% on room air.
His jugular venous pulse was at 6 cm, crackles were heard in
the bilateral lower lung elds, and lower extremities were not
edematous. Neurologic examination revealed an intact mental status, normal cranial nerve function, normal strength and
sensation throughout his arms and legs, 2+ reexes, and intact
nger-to-nose bilaterally. CT and magnetic resonance imaging
of the brain were unremarkable. Lumbar puncture revealed an
opening pressure of 20 cm of water, and cerebrospinal studies included a white blood cell count of 111/mm3, total protein of 166 g/dL, and glucose of 31 mg/dL. His cerebrospinal
microbiologic studies revealed a cryptococcal antigen titer of
1:256 and were otherwise negative. Serum cryptococcal antigen
was positive at 1:128. His serum HIV, QuantiFERON Gold,
histoplasmosis serum antigen and serology, and viral hepatitis
serologies were negative. He began treatment for cryptococcal
meningitis with ucytosine and liposomal amphotericin, and
his neurologic symptoms resolved.
Following his recovery from cryptococcal meningitis, he
underwent a CT-guided core biopsy of his left lower lobe mass,
histologically containing noncaseating granulomas (Figure 2).
Gomori methenamine silver and acid-fast stains as well as fungal
and acid-fast cultures on the biopsy specimen were negative. His
angiotensin-converting enzyme level was normal. Spirometry,
total lung capacity, and diuse capacity of carbon monoxide
were within normal limits. His workup for extrapulmonary
sarcoidosis including ophthalmology evaluation, 1,25-hydroxy
vitamin D levels, electrocardiogram, and urine calcium-tocreatinine ratio were unremarkable. With normal pulmonary
function tests and lack of extrapulmonary involvement, the
From the Division of Pulmonary and Critical Care Medicine (Adams) and
Department of Internal Medicine (Gibson), The University of Texas Southwestern
Medical Center, Dallas, Texas.
Corresponding author: Traci N. Adams, MD, Division of Pulmonary and Critical
Care Medicine, The University of Texas Southwestern Medical Center, 5323 Harry
Hines Boulevard, Dallas, TX 75219 (e-mail: tnfadams@gmail.com).
207
Figure 1. (a) Coronal and (b, c) axial CT images demonstrating a perilymphatic nodular pattern with extensive involvement of the peribronchovascular interstitium.
decision was made to manage the sarcoidosis conservatively

with serial pulmonary function testing.
DISCUSSION
An imbalance between eector and regulatory T cells may
contribute to susceptibility to infection in patients with sarcoidosis (2, 4, 5). Regulatory CD4+CD25brightFoxP3+ T cells
accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage uid, and in peripheral blood of sarcoidosis
patients (2). These cells exhibit antiproliferative activity, which
may contribute to anergy; however, because they are unable to
completely inhibit the production of tumor necrosis factor,
local inammation and granuloma formation continue to occur
(2). Immunosuppressive CD8+ T cells may also accumulate in
peripheral blood and produce anergy (4). Further, a reduced
number of CD4+ T cells and other eector T cells such as CD1drestricted natural killer cells and a decreased CD4+/CD8+ T cell
ratio are found in the peripheral blood of sarcoidosis patients,
which may inhibit their T cellmediated immunity (5).
These mechanisms of impaired T cellmediated immunity in
sarcoidosis contribute to increased susceptibility to cryptococcal
infection, which has been demonstrated in both in vitro studies
and case reports (611). Cryptococcus neoformans is an opportunistic mycosis, which begins as a primary respiratory tract
Figure 2. CT-guided core biopsy of the left lower lobe revealing granulomatous
inflammation (hematoxylin and eosin, 100).
208
infection and can disseminate hematogenously, with a propensity

to localize to the central nervous system (6). It most frequently
occurs in the setting of impaired T cellmediated immunity, and
the most common predisposing conditions include HIV, organ
failure, and prolonged treatment with glucocorticoids (79).
The largest clinical case series of C. neoformans infection revealed
that sarcoidosis accounted for 0.6% of cryptococcal cases overall
(8). Treatment with glucocorticoids and extrathoracic sarcoidosis
are independent risk factors for cryptococcal infection in these
patients (8, 11), and lung, bone, skin, and the central nervous
system are the most common sites of infection (6, 9).
1.
Mathew S, Bauer KL, Fischoeder A, Bhardwaj N, Oliver SJ. The anergic

state in sarcoidosis is associated with diminished dendritic cell function.
J Immunol 2008;181(1):746755.
2. Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S,
Kambouchner M, Valeyre D, Chapelon-Abric C, Debr P, Piette JC,
Gorochov G. The immune paradox of sarcoidosis and regulatory T cells.
J Exp Med 2006;203(2):359370.
3. Loke WS, Herbert C, Thomas PS. Sarcoidosis: immunopathogenesis and
immunological markers. Int J Chronic Dis 2013;2013:928601.
4. Planck A, Katchar K, Eklund A, Gripenbck S, Grunewald J. T-lymphocyte
activity in HLA-DR17 positive patients with active and clinically recovered sarcoidosis. Sarcoidosis Vasc Diuse Lung Dis 2003;20(2):110117.
5. Ho LP, Urban BC, Thickett DR, Davies RJ, McMichael AJ. Deciency
of a subset of T-cells with immunoregulatory properties in sarcoidosis.
Lancet 2005;365(9464):10621072.
6. Botha RJ, Wessels E. Cryptococcal meningitis in an HIV negative patient
with systemic sarcoidosis. J Clin Pathol 1999;52(12):928930.
7. Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster
DJ, Henderson H, Kauman CA, Haas DW, Saccente M, Hamill RJ,
Holloway MS, Warren RM, Dismukes WE. Cryptococcosis in human
immunodeciency virusnegative patients in the era of eective azole
therapy. Clin Infect Dis 2001;33(5):690699.
8. Bernard C, Maucort-Boulch D, Varron L, Charlier C, Sitbon K, Freymond
N, Bouhour D, Hot A, Masquelet AC, Valeyre D, Costedoat-Chalumeau
N, Etienne M, Gueit I, Jouneau S, Delaval P, Mouthon L, Pouget J,
Serratrice J, Brion JP, Vaylet F, Bremont C, Chennebault JM, Jauel S,
Broussolle C, Lortholary O, Sve P; French Cryptococcosis Study Group.
Cryptococcosis in sarcoidosis: cryptOsarc, a comparative study of 18 cases.
QJM 2013;106(6):523539.
9. Ross JJ, Katz JD. Cryptococcal meningitis and sarcoidosis. Scand J Infect
Dis 2002;34(12):937939.
10. Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal
meningitis in nonHIV-infected patients. QJM 2000;93(4):245251.
11. Jamilloux Y, Valeyre D, Lortholary O, Bernard C, Kerever S, Lelievre
L, Neel A, Broussolle C, Seve P. The spectrum of opportunistic diseases
complicating sarcoidosis. Autoimmun Rev 2015;14(1):6474.
Volume 29, Number 2
Thyroid hormone resistance and its management

Ana Marcella Rivas, MD, and Joaquin Lado-Abeal, MD, PhD
Table 1. Thyroid function panel from 2009 to 2014

The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone
Reference
resistance, is an inherited condition that occurs in
value
12/2009 10/2010 08/2011 04/2012 02/2013 07/2014
1 of 40,000 live births characterized by a reduced
TSH (mcIntUnit/mL) 0.274.20 10.37
42.41
46.62
37.70
26.39
39.00
responsiveness of target tissues to thyroid horFT4 (ng/dL)
0.931.70
3.00
1.81
2.07
1.91
1.82
1.05
mone due to mutations on the thyroid hormone
FT3 (pg/mL)
2.34.2
N/A
N/A
N/A
N/A
8.86
3.64
receptor. Patients can present with symptoms of
hyperthyroidism or hypothyroidism. They usually FT3 indicates free triiodothyronine; FT4, free thyroxine; NA, not available; TSH, thyroid-stimulating hormone.
have elevated thyroid hormones and a normal or
elevated thyroid-stimulating hormone level. Due to
their nonspecific symptomatic presentation, these patients can be misdifor the patient. Her family history was relevant for a son with
agnosed if the primary care physician is not familiar with the condition. hypothyroidism.
The patients thyroid function panels from 2009 to 2014
This can result in frustration for the patient and sometimes unnecessary
were reviewed and are presented in Table 1. During this peinvasive treatment such as radioactive iodine ablation, as in the case
riod of time she was on dierent doses of thyroid replacement
presented herein.
he syndrome of impaired sensitivity to thyroid

hormone (ISTH) is a condition of decreased tissue
sensitivity to thyroid hormone action usually caused
by germline mutations of the thyroid hormone receptor beta (THRB) gene. The mutant receptor has lower binding
anity for thyroid hormone and, as a consequence, serum
thyroid-stimulating hormone (TSH) levels remain nonsuppressed despite elevated thyroid hormones (13). We present
the case of a 66-year-old woman who was referred for evaluation of an abnormal thyroid function panel that suggested
ISTH.
CASE REPORT
A 66-year-old woman was referred for evaluation of thyroid
dysfunction. Her complaints were memory loss and intermittent gastrointestinal symptoms with alternating diarrhea and
constipation attributed to irritable bowel syndrome. In 1998,
she had been diagnosed with a thyroid condition that no one
was able to x. At that time, she had a goiter and was treated
with radioactive iodine (I-131) and was subsequently started
on thyroid replacement therapy. For nearly 30 years, she was
seen by multiple physicians who continuously modied her
thyroid hormone replacement but had been unable to normalize her thyroid hormone levels, and this resulted in frustration
therapy, her TSH remained elevated despite normal or elevated

free T4 levels. She also had magnetic resonance imaging of the
head, which showed a possible right-sided pituitary microadenoma. A thyroid ultrasound showed a normal thyroid gland
with some nonspecic nodules.
PCR amplication of THRB gene exons 10, 9, and 8 followed by gene sequencing showed a heterozygous missense mutation C>A located at exon 10. The mutation caused a change in
thyroid hormone receptor beta protein amino acid 453 proline
to threonine, P453T (Figure 1).
We recommended that the patient resume thyroid hormone
replacement with liothyronine 10 mg twice a day and levothyroxine 75 mcg daily; unfortunately, she was lost to follow up
thereafter.
DISCUSSION
We describe a case of ISTH caused by a common germline
mutation located at THRB exon 10 hot spot (4). The patient
went undiagnosed for many years. When reviewing her thyroid
From the Department of Medicine, Division of Endocrinology and Metabolism,
Mayo Clinic, Jacksonville, Florida (Rivas); and the Department of Medicine,
Division of Endocrinology, Texas Tech University Health Science Center, Lubbock,
Texas (Lado-Abeal).
Corresponding author: Ana Marcella Rivas, MD, 4500 San Pablo Road,
Jacksonville, FL 32224 (e-mail: rivasmejia.ana@mayo.edu).
209
Figure 1. Sequence analysis of the thyroid hormone receptor beta (THRB) gene showing a heterozygous mutation C>A located in exon 10. The mutation results in
a change of proline for threonine at amino acid position 453, P453T.
function tests, we noted a nonsuppressed serum TSH despite

a normal or elevated free T4 level. These abnormal values led
us to suspect THRB mutation and proceed with genetic studies, which conrmed the diagnosis. The diagnosis of ISTH requires a high degree of suspicion, and we therefore believe it is
important for the general practitioner to be able to recognize
the syndrome to avoid delay in diagnosis and unnecessary invasive treatments, such as thyroid surgery or radioactive iodine
ablation.
Thyroid hormone genomic actions are exerted by thyroid
hormone binding mostly to nuclear receptors located in the
nuclei and interaction with DNA to regulate the transcription of
target genes. Most of the cases of ISTH are caused by mutations
in the THRB gene located in chromosome 3, and these mutations most often clustered in three hot spots located in exons 8,
9, and 10. The mutant thyroid hormone receptor beta protein
has either reduced anity for T3 or abnormal interaction with
cofactors involved in thyroid hormone action, making the target
tissues refractory to thyroid hormones (57).
In 15% of cases of ISTH, a gene mutation is not identied (6). Mutations aecting thyroid hormone cell membrane
transporters and thyroid hormone metabolism have now been
described, and the concept of syndrome of reduced sensitivity
to thyroid hormone is used to encompass any defect causing
reduced eectiveness of the thyroid hormone (3).
The clinical presentation of patients with THRB mutations
is variable. Patients may present with symptoms of hyperthyroidism, hypothyroidism, or a combination of symptoms of
thyroid hormone deciency and excess depending on the level of
THRB and THRA gene expression in the target tissues (5, 6, 8).
210
Symptoms tend to decrease with age, and patients eventually

become clinically euthyroid. Goiter is one of the most common
ndings for which patients seek medical attention. Its usually
refractory and recurs after surgery or treatment with radioactive
iodine. Other common complaints include tachycardia, learning
disabilities, and hyperactivity (8).
The classic pattern of thyroid function test that these patients
present with is elevated thyroid hormones with nonsuppressed
TSH in serum. The response of TSH to thyrotropin-releasing
hormone is normal or exaggerated, and thyroidal radioiodine
uptake may be elevated (5).
ISTH can be dicult to dierentiate from TSH-producing
pituitary tumors, which present with a similar thyroid function prole. A case of coexistence of both conditions has been
reported (9). TSH-producing pituitary tumors present elevated
serum levels of T4, T3, and nonsuppressed TSH. In contrast to
patients with ISTH who may be clinically euthyroid, patients
with TSHomas usually present with symptoms of mild to severe
hyperthyroidism and compression symptoms resulting from
tumor growth (7).
When treating these patients, one should concentrate on the
patients symptoms and clinical picture instead of aiming to normalize thyroid hormone levels (5, 8). Most patients, if left alone,
adequately overcome the resistance by increased thyroid hormone secretion and therefore do not require treatment (8, 10).
Treating patients who present with normal TSH is more challenging; in these patients, administration of supraphysiological
doses of thyroid hormone might be required and, if so, should
be closely monitored. Patients who present with symptoms
of hyperthyroidism should be treated symptomatically with
Volume 29, Number 2
beta-blockers or antianxiety medications, among others, depending on their predominant symptoms (10).
1.
2.
3.
4.
Weiss RE, Weinberg M, Refeto S. Identical mutations in unrelated

families with generalized resistance to thyroid hormone occur in cytosineguanine-rich areas of the thyroid hormone receptor beta gene. Analysis
of 15 families. J Clin Invest 1993;91(6):24082415.
McDermott MT, Ridgway EC. Thyroid hormone resistance syndromes.
Am J Med 1993;94(4):424432.
Dumitrescu AM, Refeto S. The syndromes of reduced sensitivity to
thyroid hormone. Biochim Biophys Acta 2013;1830(7):39874003.
Lado Abeal J, Albero Gamboa R, Araujo Vilar D, Barca Mallo O, Bernabe Moron I, Calvo MT, Castro Piedras I, Martin Calamata J, Palos
Paz F, Pein R, Peteiro D, Victoria B. Clinical and molecular study
of ve families with resistance to thyroid hormones. Med Clin (Barc)
2011;137(12):551554.
April 2016
5.
Refeto S, Dumitrescu AM. Syndromes of reduced sensitivity to thyroid

hormone: genetic defects in hormone receptors, cell transporters and
deiodination. Best Pract Res Clin Endocrinol Metab 2007;21(2):277305.
6. Gonalves AP, Arags JM, Nobre E, Barbosa AP, Mascarenhas M. A
case of thyroid hormone resistance: a rare mutation. Arq Bras Endocrinol
Metabol 2014;58(9):962966.
7. Melmed S, Kleinberg D. Pituitary masses and tumors. In Melmed S,
Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of
Endocrinology, 12th ed. Philadelphia: Elsevier Saunders; 2011: chap 9.
8. Refeto S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid
hormone. Endocr Rev 1993;14(3):348399.
9. Teng X, Jin T, Brent GA, Wu A, Teng W, Shan Z. A patient with a
thyrotropin-secreting microadenoma and resistance to thyroid hormone
(P453T). J Clin Endocrinol Metab 2015;100(7):25112514.
10. Weiss RE, Refeto S. Treatment of resistance to thyroid hormone
primum non nocere. J Clin Endocrinol Metab 1999;84(2):401404.
Thyroid hormone resistance and its management
211
The price of a 15-year delay in diagnosis of Sheehans

syndrome
Rohan Parikh, MD, Varun Buch, BMBCh, Mitesh Makwana, MD, and Harit N. Buch, FRCP
We describe a case of a 48-year-old woman who presented with a

15-year history of recurrent episodes of hypoglycemia and hyponatremia
leading to altered behavior and generalized seizures. She underwent full
clinical assessment, endocrine tests, and a pituitary magnetic resonance
scan that showed pananterior hypopituitarism secondary to postpartum pituitary necrosis (Sheehans syndrome). She was commenced
on appropriate hormone replacement therapy, which led to significant
improvement in lethargy, anorexia, muscle weakness, and episodes of
hypoglycemia. In addition to the alleviation of her physical symptoms,
she experienced a significant improvement in her psychological wellbeing and reduction in hospital visits. This case illustrates the impact
of delay in diagnosis of an easily treatable medical condition and its
socioeconomic implications, especially for the population of a developing
country like India.
ostpartum pituitary necrosis has an insidious course

with varied manifestations. We present a case where a
delay in its diagnosis resulted in signicant morbidity
to the patient.
CASE REPORT
A 48-year-old woman was brought to the endocrine clinic
following transfer from an intensive care unit of another hospital, where she was being managed for lower respiratory infection
complicated by severe hyponatremia (serum sodium 105 mEq/L
[reference range 135155 mEq/L]) and hypoglycemia (blood
glucose 36 mg/dL [2 mmol/L]) leading to altered behavior and
generalized seizures.
She had a long history of lethargy, anorexia, and episodic
vomiting, which began insidiously a few months after her
last pregnancy and had gradually progressed over the past
15 years. She had consulted local and regional specialists and
had received symptom-driven management with no long-term
benet. Four years before presentation, she had developed
persistent and progressive back pain, stooping posture, and
reduced mobility. Imaging studies showed an osteoporotic
spine with spondylolisthesis and deformity. She required
two surgical operations over 2 years for spinal xation, with
short-term symptomatic relief. One year before presentation
she was started on 50 mcg thyroxine for hypothyroidism but
212
discontinued it due to worsening of symptoms. Over the past

2 years during intercurrent illnesses or procedures, she developed hypotension, hyponatremia, and hypoglycemia requiring
hospital admissions and had been managed with sodium and
glucose replacement.
She delivered three children at home in a rural setting.
Her last delivery had been complicated by signicant bleeding, requiring hospitalization for blood transfusion. She had
postpartum failure of lactation and her periods did not return
after the delivery, but she never sought evaluation since she had
completed her family.
On examination, she appeared well oriented but lethargic,
withdrawn, and pale. She was tachycardic with a blood pressure of 110/70 mm Hg with a postural fall of >20 mm Hg systolic. She was weak and could not sit or stand due to dizziness.
Axillary and pubic hair was scanty, and her skin was cold, pale,
and wrinkled. Her hemoglobin was 10.3 g/dL, with normocytic
blood tests, and her renal and liver function tests were normal.
As a result of the treatment she had received, her serum sodium
had risen to 121 mEq/L, and her serum potassium was normal.
Anterior pituitary hormone values, listed in Table 1, conrmed
the diagnosis of pananterior hypopituitarism.
Review of previous spinal x-rays showed spinal implant in
situ extending from L4, L5 to S1 with osteopenic bones. Dualenergy x-ray absorptiometry conrmed signicant osteoporosis,
with a spinal T score of 2.9. Magnetic resonance imaging of
the pituitary gland showed an empty sella.
A diagnosis of Sheehans syndrome was made and the patient was commenced on 75 mcg of thyroxine and 20 mg of
hydrocortisone in three divided doses. She was not started on
estrogen in view of her age and was prescribed alendronate
70 mg once a week. Within 2 weeks, she showed marked improvement in general well-being with no hypoglycemia or hyponatremia. A repeat thyroid function test conrmed adequate
replacement (Table 1). Three months later, she remained well
and had regained full mobility.
From the Department of Medicine, Civil Hospital, Ahmedabad, India (Parikh,
Makwana, H. Buch), and SAL Hospital, Ahmedabad, India (V. Buch).
Corresponding author: Harit N. Buch, MBBS, Diabetes Centre, New Cross
Hospital, Wednesfield Road, Wolverhampton, West Midlands, England, United
Kingdom WV10 0QP (e-mail: harit.buch@nhs.net).
Table 1. The patients pituitary function tests confirming anterior

hypopituitarism
Reference
range
At
presentation
On
replacement
Thyroid-stimulating
hormone (uIU/mL)
0.354.94
1.85
1.1
Free thyroxine (ng/dL)
0.701.48
0.73
1.40
Hormone
Estradiol (pg/mL)
21312
10
Luteinizing hormone
(mIU/mL)
0.909.33
0.95
Follicle-stimulating
hormone (IU/mL)
3.038.08
3.82
Prolactin (ng/mL)
1.2029.93
5.23
Peak
0.28 at 0 min
Peak plasma cortisol (ug/dL)
cortisol >20 1.36 at 30 min
after intravenous injec2.23at60min
tion of 250 ug synthetic
adrenocorticotrophic
hormone (cosyntropin)
DISCUSSION
Sheehans syndrome is caused by pituitary necrosis secondary to hemorrhagic hypovolemic shock during the peripartum
period (1). Enlargement of the pituitary gland, small sella size,
disseminated intravascular coagulation, and autoimmunity have
been suggested to play a role in the pathogenesis of Sheehans
syndrome in women who suer from severe postpartum hemorrhage (2). Improvement in obstetric care and the availability of blood transfusion have led to a signicant reduction in
the frequency of Sheehans syndrome in the developed world.
However, the entity remains one of the most common causes
of hypopituitarism in the developing world (2).
Failure of postpartum lactation and failure of resumption of
menses after delivery are the most common presenting symptoms (2). However, patients can present with a wide variety of
symptoms, including feeling generally unwell, or with symptoms attributable to deciency of individual hormones, e.g.,
constipation, fatigue, lethargy, dizziness, depression, or weight
loss (37). Rarely, patients may present with hypoglycemic coma
(5, 6). Although a small percentage of patients have an abrupt
onset of severe hypopituitarism immediately after delivery, typically the onset of Sheehans syndrome is insidious (7, 8). This
could make an early diagnosis dicult, and a high index of
suspicion is needed when patients present with a combination of
the above symptoms with a history of peripartum hemorrhage.
Once suspected, the diagnosis can be conrmed with pituitary
April 2016
function tests and imaging, which are accessible and aordable

for most patients, even in the developing world (2).
In our patient, there was a long delay in arriving at the diagnosis despite several clues, including secondary amenorrhea,
premature osteoporosis, unexplained signicant hyponatremia,
hypoglycemia during acute stress, and worsening symptoms
after thyroxine administration indicating concomitant hypocortisolemia. Several possible reasons could have contributed to this
delay. Appropriate guidance was not provided on discharge after
her eventful delivery and postpartum hemorrhage. The patient
did not seek help for secondary amenorrhea for several years.
Once she presented to health professionals, her management
remained symptom-driven for a number of years without an
attempt to diagnose the underlying cause.
The patient and her family had to pay a heavy price for this
delay in diagnosis in the form of a physical, psychological, social, and nancial burden. The patient endured poor health for
several years, as well as impaired mobility, spinal deformity requiring two operations, repeated hospitalizations, and episodes
of life-threatening acute illness related to adrenal crises. She had
to frequently travel long distances, in a state of failing health, to
seek specialist help. Her husband, who was her main caregiver,
needed to be o work for a combined period of over 100 days
during the previous 2 years. There was a considerable strain
in family relationships due to the patients chronic ill health.
Lastly, the nancial burden on the lower-middle-class family was
immense, with a combined cost of Rs.600,000 (>US$10,000),
which was >2 years of the familys annual income. Once the
correct diagnosis was made, her monthly cost for medications
was reduced to Rs.700 (US$14) a month.
Sheehan HL. Postpartum necrosis of the anterior pituitary. J Pathol Bacteriol
1937;45:189214.
2. Keletimur F. Sheehans syndrome. Pituitary 2003;6(4):181188
3. Sanyal D, Raychaudhuri M. Varied presentations of Sheehans syndrome at diagnosis: a review of 18 patients. Indian J Endocrinol Metab
2012;16(Suppl 2):S300S301
4. Qadri MI, Mushtaq MB, Qazi I, Yousuf S, Rashid A. Sheehans
syndrome presenting as major depressive disorder. Iran J Med Sci
2015;40(1):7376.
5. Dosi RV, Bhatt NR, Patell RD, Raj RR. Recurrent hypoglycemia . . . :
a less well-known presentation of Sheehans syndrome J Postgrad Med
2013;59(4):318320.
6. Kumar N, Singh P, Kumar J, Dhanwal DK. Recurrent hypoglycaemia: a delayed presentation of Sheehan syndrome. BMJ Case Rep
2014;2014:bcr2013200991.
7. Schrager S, Sabo L. Sheehan syndrome: a rare complication of postpartum
hemorrhage. J Am Board Fam Pract 2001;14(5):389391.
8. Boulanger E, Pagniez D, Roue S, Binaut R, Valat AS, Provost N,
Leroy R, Codaccioni X, Dequiedt P. Sheehan syndrome presenting as early post-partum hyponatraemia. Nephrol Dial Transplant
1999;14(11):27142715.
1.
The price of a 15-year delay in diagnosis of Sheehans syndrome
213
Linezolid-induced serotonin toxicity in a patient not taking

monoamine oxidase inhibitors or serotonin receptor
antagonists
Jacob Sutton, DO, Jeff Stroup, PharmD, BCPS, and Mo Som, DO, MS
Linezolid is an oxazolidinone antibiotic with weak monoamine oxidase

(MAO) type A and MAO type B inhibitory effects. Linezolid has been
associated with serotonin toxicity when used concomitantly with multiple
medications that are known to increase serotonin concentrations. We
report the case of a 65-year-old woman with signs and symptoms of
serotonin toxicity following administration of linezolid for treatment of
methicillin-resistant Staphylococcus aureus pneumonia.
inezolid is the rst oxazolidinone antibiotic approved

for use in the United States for treatment of resistant
gram-positive bacterial infections including vancomycin-resistant enterococci, Staphylococcus aureus including
methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (1). It has nonselective monoamine oxidase
(MAO) type A and MAO type B inhibitory eects (2). It has
been associated with serotonin toxicity with concomitant use
of multiple medications, including selective serotonin reuptake
inhibitors, serotonin-norepinephrine reuptake inhibitors, MAO
inhibitors, tricyclic antidepressants, meperidine, and carbidopalevodopa (1).
CASE REPORT
A 65-year-old woman dependent on oxygen initially presented to the emergency department complaining of dyspnea,
fevers, chills, and productive cough for 3 to 4 days. She was febrile on arrival, with a temperature of 39.3C, and tachycardic,
with a heart rate of 122 beats/minute. Her serum creatinine
was 1.95 mg/dL. She was admitted to the intensive care unit
and started on piperacillin-tazobactam and levooxacin. After
volume resuscitation, her acute kidney injury resolved. Blood
cultures drawn on admission remained negative. IgG serologies for Legionella pneumophila, Mycoplasma pneumoniae, and
Chlamydia pneumonia were negative. The patient continued
to improve. On the date of discharge, an expectorated sputum
culture taken on admission grew MRSA. She was discharged
home with 10 days of linezolid 600 mg twice daily for treatment
of MRSA pneumonia. She was not given a dose of linezolid
prior to discharge from the hospital.
The patient presented to the emergency department 5 days
later following a syncopal episode at home. She had injuries to
214
her left scalp, left shoulder, left elbow, and bilateral hands. Computed tomography (CT) of the brain and multiple extremity
x-rays showed no acute pathology. An electrocardiogram showed
nonspecic T wave changes, with QTc, QRS, and PR intervals
within normal limits. She was given intravenous lorazepam for
agitation. Her vital signs remained stable and she was admitted
to the hospital.
Her family reported that she began having increasing agitation following her rst dose of linezolid 5 days earlier. The
patient reported new-onset insomnia, increased restlessness,
increased bowel movements, tremor, and visual hallucinations
after her rst dose of linezolid. She also reported a feeling of
increasing warmth, but denied any subjective or documented
fevers. Physical exam was positive for ocular clonus, equal mydriasis with reactive pupils, and muscular clonus in the bilateral
lower extremities. She did not have autonomic instability or
hyperthermia. She reported taking uoxetine 14 months prior
to her admission. Otherwise, she was not prescribed any medications that are known to increase serotonin concentrations,
including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, MAO inhibitors, and tricyclic
antidepressants. Her linezolid was discontinued. She was treated
with an oral benzodiazepine. The day following admission, her
signs and symptoms of serotonin toxicity completely resolved.
She was discharged home later that day to complete a 10-day
course of clindamycin for MRSA pneumonia.
DISCUSSION
Linezolid inhibits protein synthesis by binding to 23S on
the 50S subunit of bacterial ribosomal DNA (3). Linezolid has
activity against aerobic and anaerobic gram-positive organisms,
including MRSA, vancomycin-resistant Enterococcus faecium,
and Streptococcus pneumoniae (4, 5). Linezolid has been approved for the treatment of gram-positive infections causing
nosocomial pneumonia, community-acquired pneumonia,
From the Department of Medicine, Oklahoma State University Medical Center,
Tulsa, Oklahoma (Sutton); and Oklahoma State University Center for Health
Sciences, Tulsa, Oklahoma (Stroup, Som).
Corresponding author: Mo Som, DO, MS, Oklahoma State University Center for
Health Sciences, 717 S. Houston, Tulsa, OK 714127 (e-mail: mousumi.som@
okstate.edu).
complicated and uncomplicated skin and structure infections,

and vancomycin-resistant Enterococcus faecium infections including bacteremia (2).
Linezolid exhibits weak, reversible MAO A and MAO B
inhibition (1). MAO enzymes are responsible for metabolism of
the monoamine neurotransmitters epinephrine, norepinephrine,
serotonin, and dopamine (6). Serotonin toxicity was not observed with coadministration of linezolid and other serotonergic
drugs in phase I, II, or III clinical trials (7). However, there are
multiple postmarketing case reports of patients developing serotonin syndrome when taking linezolid concurrently with medications known to cause increases in serotonin concentrations (1).
Serotonin syndrome is caused by increased serotonergic activity in the central nervous system and has been observed in all
age groups with an increasing incidence (8, 9). Physical exam
ndings of serotonin syndrome include hyperthermia, agitation,
ocular clonus, mydriasis, tremor, akathisia, hyperreexia, muscular clonus, muscle rigidity, and increased bowel sounds (8).
Serotonin syndrome is a clinical diagnosis made using the
Hunter toxicity decision rules. Criteria for diagnosis include
the use of a serotonergic drug and one of the following (10):
Spontaneous clonus
Inducible clonus plus agitation or diaphoresis
Ocular clonus plus agitation or diaphoresis
Tremor plus hyperreexia
Hypertonia plus temperature <38C plus ocular clonus
or inducible clonus
The Hunter criteria are 84% sensitive and 97% specic for
the diagnosis of serotonin syndrome (10). Patients with severe
serotonin syndrome demonstrate autonomic instability and
severe hyperthermia.
Serotonin syndrome management includes the initial identication of the toxidrome and discontinuation of all serotonergic
April 2016
drugs. Additional management of serotonin syndrome includes

supportive care and benzodiazepines for sedation. Patients with
more severe cases of serotonin syndrome may benet from the
use of the serotonin receptor antagonist cyproheptadine (4 mg
three times daily) (11). Patients with autonomic instability and
severe hyperthermia (temperature <41C) should be managed
in the intensive care unit. These patients should be sedated,
intubated, and managed with paralytic medications (8).
1.
Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with

the use of linezolid: a review of postmarketing data. Clin Infect Dis
2006;42(11):15781583.
2. Linezolid [package insert]. New York, NY: Pzer, 2014.
3. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA. Linezolid-associated
serotonin syndrome after concomitant treatment with citalopram and
mirtazepine in a critically ill bone marrow transplant recipient. J Intensive
Care Med 2005;20(6):351353.
4. Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet 2003;42(13):1129
1140.
5. Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action,
and mechanism of resistance. Int J Antimicrob Agents 2004;23(2):113119.
6. Yamada M, Yasuhara H. Clinical pharmacology of MAO inhibitors: safety
and future. Neurotoxicology 2004;25(12):215221.
7. Jones SL, Athan E, OBrien D. Serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother 2004;54(1):289
290.
8. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;
352(11):11121120.
9. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of
2 cases and review of the literature. Medicine (Baltimore) 2000;79(4):201
209.
10. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The
Hunter serotonin toxicity criteria: simple and accurate diagnostic decision
rules for serotonin toxicity. QJM 2003;96(9):635642.
11. Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome
with cyproheptadine. J Emerg Med 1998;16(4):615619.
Linezolid-induced serotonin toxicity in a patient not taking monoamine oxidase inhibitors or serotonin receptor antagonists
215
Baylor news
Baylor University Medical Center
at Dallas opens womb transplant

clinical trial
(BUMC) is among the first in the US to conduct
a new clinical trial that will implant wombs in
10 women with absolute uterine factor infertility, meaning their uterus is nonfunctioning or
nonexistent. The hope is to give these women
a chance to become pregnant and carry a
child full term. The researchers, who will
conduct the clinical trial through Baylor Scott
& White Research Institute, anticipate that
the first baby to be carried by a transplanted
womb in the US could be born in 2017. The
complex process involves a multidisciplinary
collaboration at BUMC among obstetriciangynecologists, fertility specialists, and the
transplant team.
The entire process of transplantation, fertilization, prenatal care, and deliverythey're all
connected as part of this study, and they'll all
take place at Baylor University Medical Center
at Dallas, said Giuliano Testa, MD, principal
investigator and surgical chief of abdominal
transplantation at BUMC. All of these components are integrated with one goal in mind:
helping women who've been previously unable
to have a baby.
Investigators will seek recipients between
ages 20 and 35 years old with absolute uterine
factor infertility, intact ovaries, and the desire to
carry a baby to term, among other criteria. Living
donors should be between 40 and 65 years old
and have previously carried at least one baby to
term, among other criteria (menopause is not
required).
Prior to the surgery, study participants will
undergo in vitro fertilization (IVF); qualified patients must have healthy and otherwise normal
functioning ovaries. After surgery, the women
will be monitored and may be eligible for an
embryo produced from earlier IVF procedures
to be transferred as early as a year following the
womb transplant. If implantation is successful
and the recipient becomes pregnant, she will be
routinely monitored until her baby is delivered
by cesarean section. Because carrying foreign
body tissue can increase infection risk and requires taking regular antirejection medication,
women in this study will undergo a hysterectomy
after one or two successful pregnancies. For
this reason, the women who want a second
216
pregnancy will have shorter windows of time

between births.
If 2017 brings babies successfully born from
transplanted wombs, new options for women
hoping to bear children may come by the end of
the decade, or sooner. If we're as successful as
we believe we'll be in helping women have fullterm healthy pregnancies with the transplantations, then we will open this option to every
woman who is willing to undergo a transplant
to have a child, Dr. Testa said.
Baylor University Medical Center at
Dallas earns prestigious pancreas

center designation
BUMC has been named aNational Pancreas
Foundation (NPF) Center, one of only 30 facilities in the country to receive this prestigious
designation from the health advocacy group.
BUMC is the only NPF Center in Texas and
all surrounding states including Arkansas,
Louisiana, New Mexico, and Oklahoma. The
NPF, a nonprofit group that works to provide
education and hope for patients with pancreatitis and pancreatic cancer, created the
designation to help patients find high-quality,
multidisciplinary care. Designated centers also
seek to advance research and awareness for
pancreatitis and related conditions among
community physicians, allied health professionals, patients, families, and the general
public.
Having the NPF Center designation means
patients will know that we provide a high level
of patient-centered care either for the treatment
of their disease or to get an expert second opinion, said Scott Celinksi, MD, medical director of
the Pancreatic Cancer Research and Treatment
Center at BUMC.
Approved NPF Centers must go through an
extensive auditing process and meet the criteria
developed by a task force of clinical specialists
andpatientadvocates. The criteria included having required expert physician specialties, along
with more patient-focused programs such as
pain management, psychosocial support, and
more. The clinical team at the Pancreatic Cancer
Research and Treatment Center includes physicians from a variety of specialties, including
gastroenterology, interventional endoscopy, surgery, oncology, radiology, pathology, pain management, and genetics. Highly trained nurses,
genetic counselors, and nutritionists also serve
as team members. These specialists are recognized leaders in pancreatic disease care and
can offer diagnostic and treatment options that
are not available at most hospitals.
BUMC offers in-depth expertise for many
pancreatic diseases, including treatment for
chronic pancreatitis through auto-islet cell
transplants, performed by medical teams
within the Baylor Annette C. and Harold C.
Simmons Transplant Institute. In the procedure, the pancreas and spleen are removed
and the patient's own islet cells are extracted.
They are then infused into the patient's liver,
where they take hold and produce insulin to
prevent diabetes.
The Liver and Pancreas Disease Center, another unique program at BUMC, is dedicated to
treating patients with liver and pancreas cancer.
This center's team coordinates each patient's
tumor management and plan of care among the
specialists on the BUMC medical staff. Since the
program's inception in 1998, more than 5000
patients have received treatment.
ACCOLADES
William C. Roberts, MD, director of the
Baylor Heart and Vascular Institute at BUMC
and editor in chief of BUMC Proceedings
and The American Journal of Cardiology,
received the 2016 Lifetime Achievement
Award from the American College of
Cardiology. The awardwhich honors an
individual who has had a lifetime of outstanding achievements in the field of cardiovascular disease and has served as a
role model through service, basic or clinical
research, and teachingwas presented at
the college's 65th Annual Scientific Session
in Chicago on April 4.
The Texas Neurological Society honored
Stuart Black, MD, chief of neurology at
BUMC and co-director of the Baylor Scott
& White Health Neuroscience Governance
Council, with a Lifetime Achievement
Award at the societys annual winter conference held February 5 to 7, 2016. The
Lifetime Achievement Award is a peer
recognition award to honor members who
distinguish themselves as leaders in the
neurological profession and contribute their
time and effort on behalf of the society.
Baylor Scott & White Health and Tenet
complete joint venture to own five

North Texas hospitals
Baylor Scott & White Health and Tenet
Healthcare Corporation have completed the
previously announced joint venture to own
five hospitals in North Texas. The facilities
included are Centennial Medical Center in
Frisco, Doctors Hospital at White Rock Lake in
Dallas, Lake Pointe Medical Center in Rowlett,
Texas Regional Medical Center at Sunnyvale,
and Baylor Scott & White Medical Center
Garland. The first four hospitals will transition to Baylor Scott & White Health branding
as early as the spring of 2016. Additionally,
physicians, advanced practice providers, and
other employees of Tenet's North Texas physician group will transition to Baylor Scott &
White Health's physician group, HealthTexas
Provider Network.
We have already made meaningful progress in advancing population health through our
physicians' participation in the Baylor Scott &
White Quality Alliance, a leading local accountable care organization, and the completion of
this joint venture is an important next step in
coordinating top-quality, value-based care in
North Texas, said Trevor Fetter, chairman and
CEO of Tenet Healthcare.
UPCOMING CME PROGRAMS

The A. Webb Roberts Center for Continuing Education of Baylor Scott & White Health is
offering the following programs:
Second Annual Skin Cancer Conference, April 2, 2016, Baylor Charles A. Sammons
Cancer Center, Dallas, Texas
IBD Conference, April 16, 2016, Roberts Hospital, 17th Floor Conference Center, Dallas,
Texas
Palliative Care and Oncology, April 16, 2016, Baylor Charles A. Sammons Cancer Center,
Dallas, Texas
Third Annual Oncology Update for Primary Care Providers, April 30, 2016, Sheraton
McKinney, McKinney, Texas
Current Trends in Complex Specialty Care in Patients, April 30, 2016, Baylor Scott &
White Medical CenterPlano
Southwest Regional Primary Care Physician Education Conference, May 2, 2016,
Hilton Garden Inn, Granbury, Texas
Pulmonary and Critical Care Medicine Symposium, May 7, 2016, Baylor Charles A.
Sammons Cancer Center, Dallas, Texas
Seventh Annual Stroke and Neurological Disease Conference, May 21, 2016, Westin
Galleria, Dallas, Texas
Complex Care: Treatment Trends and Improved Outcomes, August 13, 2016, Santa
Fe, New Mexico
Complex Care: Treatment Trends and Improved Outcomes, September 17, 2016,
Greenville, Texas
Chest Cancer 2016, October 28, 2016, Baylor Charles A. Sammons Cancer Center, Dallas, Texas
For more information, call 214.820.2317 or visit www.cmebaylor.org.
RECENT GRANTS
A novel function of Itch in controlling
IL-17induced inammation in colon
cancer
Principal investigator: Venuprasad
Poojary, PhD
Sponsor: Cancer Prevention Research
Institute of Texas
Funding: $900,000
Award period: 6/1/20165/31/2018
Cellular therapy for cancerC1
Principal investigator: Carlos Becerra, MD
Institute of Texas
Funding: $50,956
Award period: 7/1/20156/30/2016
Cellular therapy for cancerAC
Principal investigator: Carlos Becerra, MD
Institute of Texas
Funding: $6,629
Award period: 7/1/20156/30/2016
April 2016
Cellular therapy for cancerC2

Principal investigator: Joseph Fay, MD
Institute of Texas
Funding: $112,127
Award period: 7/1/20156/30/2016
Louisiana clinical data research
network subcontract agreement
Principal investigator: Andrew Masica,
MD
Sponsor: Louisiana Public Health
Institute/Patient Centered Oral Research
Institute
Funding: $307,300
Award period: 9/18/20159/17/2016
Nurse-driven acute stroke care study
Principal investigator: Jamee Gatzemeier
Sponsor: UT Southwestern Medical
Center/Lone Star Stroke Consortium
Funding: $15,000
Award period: 8/1/20151/31/2017
Baylor news
A policy-relevant US trauma care

system pragmatic trial for PTSD and
comorbidity
Principal investigator: Ann Marie Warren,
PhD
Sponsor: University of Washington/
National Institutes of Health
Funding: $7,925
Award period: 8/1/20157/31/2016
Metabolomic salivary biomarkers for
oral cancer detection
Principal investigator: Teodoro Bottiglieri,
PhD
Sponsor: Texas A&M University/National
Institutes of Health
Funding: $49,914
Award period: 6/1/20155/31/2017
217
PHILANTHROPY NOTES
Trisha Wilson estate gift will leave
lasting impact on heart patients

Trisha Wilson knows a thing or two about
building a legacy that will last for generations.
As the founder of interior architectural design
firm Trisha Associates, she has designed interiors for some of the world's most luxurious
hotels, palaces, casinos, private residences,
resortseven 747s. More than 1 million fivestar hotel rooms worldwide feature interiors
dreamed up by Trisha and her team.
Trisha will leave a legacy in her hometown
of Dallas, too, through a $5 million estate gift
to establish the Trisha Wilson Distinguished
Chair in Cardiology at BUMC. This chair will
support research, education, and programmatic initiatives benefiting heart and vascular
patients for many years to come. I know a
lot of people donate to cardiology causes,
Trisha said, but I just dont think you can do
enough. Heart disease is the biggest killer
there is.
This estate gift is the latest in Trisha's history of giving to Baylor. Her support began in
1994 and has grown over the years, including
a $250,000 gift for the Emergency Department
at BUMC in 2008 in honor of close friend
Leonard Riggs, MD. Trisha also has served for
many years on the Baylor Health Care System
Foundation board.
Giving away a meaningful percentage
of her estate is important to Trisha. I have
godchildren and nieces and now Ill have a
husband with children, but it's really important
for me to give back. Even if I had children, I
wouldnt leave it all to themand wouldnt
expect them to know what I would want them
to do with my estate. It was also important for
me to get this done now because you never
know what's going to happen. You could get
hit by a bus tomorrow!
Baylor to offer innovative clinical
trial for one of the deadliest cancers

A generous contribution from The
Jeanne Shelby Fund for Cancer Research at
New cardiac device reduces stroke
risk for patients with atrial fibrillation

The WatchmanTM Left Atrial Appendage
Closure, a new implantable cardiac device the
size of a quarter, is offering patients with atrial
218
Communities Foundation of Texas is funding

a new, more effective clinical trial option that
aims to make inoperable pancreas cancer
operable. Under the direction of research investigators Carlos Becerra, MD, medical director of the Swim Across America Innovative
Clinical Trials Center and assistant chief of
oncology, and Scott Celinski, MD, director of
the Pancreas Cancer Research and Treatment
Center, this clinical trial will combine the inflammation-reducing drug anakinra with a
three-drug chemotherapy regimen that was
recently proven highly effective in a clinical
trial. Anakinra has shown great promise in a
breast cancer clinical trial at Baylor, and since
all the drugs to be used in this trial are already
FDA approved, it is expected to begin before
the end of the year.
By giving patients the most effective chemotherapy available before surgery, we can kill
microscopic cancer that has spread away from
the original tumor and maximize our chances
for a surgical cure of pancreas cancer, said Dr.
Celinski. This trial is important in our pursuit
of defeating pancreas cancer.
As additional funding becomes available,
the samples collected from patients in the
clinical trial will be analyzed for circulating
tumor-specific DNA. The aim of these analyses
is to help identify reliable biomarkers that can
be used as a screening test for early detection
or monitoring of the disease.
Caroline Greenstone was just 8 years old

when her dad, David, had to share some bad
news. Her mother had cancer. Within weeks,
he had more bad news. His own mother was
also diagnosed with cancer.
Caroline didnt know what was going to
happen, said David, a trial attorney and one
of the founding members of Simon Greenstone
Panatier Bartlett, PC. His wife, Joanna, had
transitional cell carcinoma, a type of bladder cancer, and began treatment at BUMC.
His mother, Karen Stern, was diagnosed with

myelofibrosis and receives care at another
hospital.
Caroline wanted to know: What can we do
to help mommy? What can we do to help other
people that are dealing with this type of thing?
How can we fight back? David said. She
fought back by forming the Cancer Fighters
Club with her little sister, Olivia, then 5. They
formed the club to raise money to help their
mother, grandmother, and others going through
cancer. This organization started as a way for
her to try to get some control, said David, who
helped his girls establish the Cancer Fighters
Club as an official fund through the Dallas
Jewish Community Foundation.
The Cancer Fighters Club hosts special
fundraising events, and the Greenstone girls
choose where the money goes. Theyve selected charities such as the American Cancer
Society and Myeloproliferative Research
Foundation. Every time weve done a fundraiser, weve given to Baylor, David said.
That's important to us because it made
such a difference in our lives. After surgery
and intense chemotherapy at Baylor, Joanna
is doing well.
The girls fundraising efforts started with
lemonade and coffee stands outside their
house. In the past 3 years, though, theyve
had a roller skating party to roll over cancer,
and after their mother finished her cancer
treatments, the family hosted a party with a
waterslide at their house and invited friends,
family, and neighbors. Admission was free, and
donations were welcome.
The girls, whove raised nearly $20,000
so far, have no plans for slowing down, leaving plenty of room for Emma, now 3, to get
involved as she gets older. The most important
thing theyve learned is that they can actually
make a difference, David said. They actually
can fight back.
For information on how you can support
these or other initiatives at Baylor, please contact the Foundation at 214.820.3136.
fibrillation an alternative to long-term blood thinner use to reduce the risk of stroke. The approach was first tested in clinical trials in 2010
through 2013 at Baylor Jack and Jane Hamilton
Heart and Vascular Hospital. Now physicians on
the medical staff are early adopters of the technology they helped assess during clinical trials.
Our greatest worry is that patients who have
atrial fibrillation will have a stroke, said Kevin
Wheelan, MD, chief of staff at Baylor Hamilton
After mom's diagnosis, Greenstone
girls give back to Baylor
Volume 29, Number 2
Heart and Vascular Hospital. Research has

shown that patients with this type of heart arrhythmia are five times more likely to have a
stroke. Blood thinners have been the standard
course of treatment, but, for some patients, an
alternative such as this device is a better longterm approach.
The parachute-shaped Watchman device is
implanted using minimally invasive techniques.
Cardiologists perform the hour-long procedure
in a catheterization lab while the patient is under
light general anesthesia. Generally patients are
released from the hospital in less than 24 hours
after the procedure and gradually decrease their
use of blood thinner medication over time, under
supervision of their cardiologist.
Caring for the special heart: new
adult congenital heart disease center

opens
A new center at the Baylor Jack and Jane
Hamilton Heart and Vascular Hospital is focused
on caring for the rising number of adults with
health complications due to congenital heart
disease. Led by Medical Director Ari M. Cedars,
MD, who recently joined the medical staff at
BUMC, the new Center for Adult Congenital
Heart Disease cares for patients born with a
defect in one or more structures of the heart or
blood vessels. These are the most common type
of birth defects, affecting about 1% of all babies born each year. Thanks to rapidly advancing technology and new methods of treatment,
these children can now live into adulthood. But
while survival rates are rising, so is the incidence of complications in adults with the condition, even after repair in childhood.
One of the problems physicians face in
treating these conditions in adults is the misperception that corrective surgery in childhood
permanently cures congenital heart defects,
Dr. Cedars said. Surgical technology and techniques were not nearly as refined in the 1950s
and 1960s, when many of the procedures to
treat pediatric heart problems were developed.
And even under optimal conditions, patients
born with abnormal cardiac anatomy are going
to be subject to long-term consequences as a
result of their repair.
Not only do those operative repairs deteriorate over time, but another factor begins to
April 2016
have an effect in adult patients: the aging process. Adult congenital heart disease patients
can face a triple threat: an abnormal heart
structure, a deteriorating surgical repair, and
the acquired heart problems that many older
people develop. Theres nothing about being
born with a heart defect that protects you from
ultimately developing coronary heart disease,
heart failure, or abnormal heart rhythms, said
Dr. Cedars. (See Dr. Cedars commentary on
adult congenital heart disease on pp. 174175
of this issue.)
Renowned cardiothoracic surgeon
joins The Heart Hospital Baylor Plano

Bruce Lytle, MD, a cardiothoracic surgeon who until recently served as chairman
of Cleveland Clinic's Sydell and Arnold Miller
Family Heart & Vascular Institute, has joined
The Heart Hospital Baylor Plano (THHBP). He
will serve in the newly created role of chairman of cardiovascular strategic development
and planning for cardiovascular medicine and
surgery.
Based on Dr. Lytles previous experience of
leading an internationally recognized heart and
vascular institute, he brings a unique combination of talent and expertise to the leadership of
our institution, said Mark Valentine, president,
TTHBP.
Dr. Lytle joined Cleveland Clinics thoracic
and cardiovascular surgery department in 1978
after receiving his medical degree from Harvard
and completing residencies at Massachusetts
General Hospital. While chairman of Cleveland
Clinic's heart and vascular institute, he oversaw
nearly 100 cardiologists and 25 heart and vascular surgeons who performed more than 7600
surgeries a year. He is credited with the conception and growth of the heart centers national affiliation program. Baylor Jack and Jane Hamilton
Heart and Vascular Hospital, BUMC, and TTHBP
are affiliated with the Cleveland Clinic to share
best practices, coordinate care, and develop
programs to improve quality and patient safety.
Dallas, Plano researchers test new
device to treat advanced heart failure

Researchers at the Baylor Annette C. and
Harold C. Simmons Transplant Institute and
TTHBP have begun studying a next-generation
Baylor news
heart device that could give long-term solutions

for patients with advanced heart failure. At about
the size of a small doorknob, the devicethe
HeartMate III Left Ventricular Assist System
helps circulate blood through the body and could
help certain patients avoid heart transplant
surgery. The research is part of Momentum
III, a nationwide trial by Thoratec Corporation,
which also manufactured the HeartMate I
and HeartMate II. The new trial compares the
HeartMate III with the FDA-approved HeartMate
II to determine if the new device is both safer
and more effective for people whose hearts
dont function properly and either dont want
or dont qualify for a heart transplant.
Half the size of its HeartMate II predecessor,
the HeartMate III device attaches to the heart's
wall, with one end connecting to theaorta. An
external battery system powers the device,
which can pump up to 10 L of blood per minute.
The new version of the technology is designed
to reduce complications, which can include infection, bleeding, and thromboembolic events.
The science behind the new design is
sound, so we hope this will decrease the risk of
complications, said Shelley A. Hall, MD, FACC,
chief of transplant cardiology and mechanical circulatory support/heart failure at BUMC.
Technology is continuing to move forward at a
much faster rate than our ability to treat heart
failure with pills or by modifying the immune
system after transplant. This is a very promising
therapy for our patients with advanced heart
failure.
The Heart Hospital Baylor Plano
earns top rating for cardiovascular

care
THHBP was recognized by The Society of
Thoracic Surgeons as a three-star quality program in coronary bypass surgery, aortic valve
replacement, and aortic valve replacement and
coronary bypass grafting. A three-star rating is
the highest achievable, and those three procedural groupings are the only ones where
such ratings are awarded. Only 1% of the
1013 cardiac surgery hospitals in the United
States reporting to the Society of Thoracic
Surgeons registry received three-star ratings
in all categories based on the society's quality
methodology.
219
On John Keats and Blue Zones

John Davis Cantwell, MD
n route to Sardinia, to visit hill towns in the so-called

longevity Blue Zones, we had a brief stopover in Rome.
It allowed time only to see the apartment where physician-poet John Keats spent the last 3 months of his
life (separated from his ancee, Fanny Brawne) and to reect
upon his all-too-brief life. I also wanted to visit his grave, to
place some daisies on it, as did his physician, Dr. James Clark.
It seemed to me the least the latter could have done, having
misdiagnosed his pulmonary consumption and maltreating the
weak and severely ill patient with blood lettings and a nearstarvation diet.
JOHN KEATS
Keats was just 51, a handsome lad (Figure 1) who seemed
anything but an athlete and a ghter. He was good at games
and (according to a classmate) would ght anyone, morning,
noon, and night. He ailed away at the butchers son when he
caught the latter tormenting a kitten.
Born in 1795, he was orphaned at a young age, after his
father had a fatal riding accident and his mother succumbed to
consumption (tuberculosis). Keats nursed his dying mother
and probably contracted the disease as a result. A year after her
death, Keats became an apprentice to Thomas Hammond, an
apothecary-surgeon practicing in a northern suburb of London.
He clashed with Hammond, apparently an alcohol abuser, and
moved to separate lodging.
Keats began to write poetry in his teens. Several years later he
continued to pursue a medical career at Guys Hospital, where
he met a lifelong friend, Joseph Severn. The patients at Guys
Hospital were largely drawn from the nearby slums. Observing
the various diseases, Keats once concluded that worldly honors
seemed meaningless when one considers young women with
cancer.
While at the hospital, Keats discovered the great books and
became inuenced by the likes of Shakespeare and Wordsworth.
He diered from his fellow medical students in expression,
dress, and actions. The stomach appeared to him like a brood
of callow nestlings, opening their capacious mouths, yearning
and gasping for sustenance. He started to dress like poets did,
turning his collar down and wearing a ribbon around his neck.
He also grew a moustache.
220
Figure 1. John Keats. Source: National Portrait Gallery, London.
In the lecture hall, Keats seemed to sit apart and to be

absorbed in something else. During one lecture he observed a
sunbeam into the room and with it a whole troop of creatures
oating in the ray; and I was o with them to fairyland.
From Piedmont Heart Institute, Atlanta, Georgia.
Corresponding author: John Davis Cantwell, MD, Piedmont Heart Institute,
275 Collier Road, NW, Suite 500, Atlanta, GA 30309 (e-mail: john.cantwell@
piedmont.org).
His physician in Rome, Dr. Clark, initially thought a gastric

condition was causing mental exertion. A detailed family
history should have alerted Clark as to the correct diagnosis.
Clarks treatment likely hastened Keats death. He was bled
(despite his weakness and bloody sputum) and placed on a
literally starvation diet, consisting of an anchovy and a piece
of bread daily.
As a poet, Keats sold only several hundred copies of his
books in his brief lifetime. Several were severely criticized in
reviews. In one, published in Blackwoods Magazine, the reviewer wrote:
It is better and a wiser thing to be a starved apothecary (and
physician) than a starved poet; so back to the shop, Mr. John,
back to the plasters, pills and ointments.
Figure 2. Keats apartment building in Rome (on the right of the Spanish Steps).
A rotation with Dr. William Lucas, Jr., called by some the

butcher of the hospital, seemed to turn Keats away from medicine. Lucas cut amongst the most important parts as though
they were only skin, making us all shutter from apprehension
of his opening arteries or committing some other error. Keats
felt his own dexterity was limited, so he put down the lancet
for good and turned to poetry.
Keats met Fanny Brawne, the love of his life, in 1818, the
same year his brother died of tuberculosis. In February 1820,
Keats began having hemoptysis into the bedsheets. He illuminated the latter with a candle and, drawing from his medical
background, stated: This is very unfortunate. I know the color
of that blood. Its arterial blood. Theres no mistaking that color.
That blood is my death warrant. I must die.
His physician sent him to Rome, thinking that the warm
weather would help. Joseph Severn accompanied him. It took
several months to arrive, in November, when the weather had
turned cold. Keats and Severn rented an apartment on the second oor of a building near the Spanish Steps (Figure 2). He was
essentially conned to a small bedroom (Figure 3), nursed by
Severn. It became too painful for Keats to read Fanny Brawnes
last letters, which remained unopened and were later buried
with him.
Figure 3. The bedroom where Keats was confined in Rome.

April 2016
Little wonder that for his epitaph Keats requested that no

name be placed on his tomb in the Protestant Cemetery in Rome
(Figure 4), only Here lies one whose name was writ in water.
In his own mind, however, Keats had condence in his writing
skills, once correctly deantly declaring to one of his brothers
that he would be among the English poets after his death. Keats
died quietly in Severns arms. Years later Severn would request
to be buried next to Keats.
One of Keats biggest champions was Percy Shelley, who
continued to correspond with Keats while the latter was in
Rome, and who wrote an elegy (Adonais) to Keats a few
months after the latters death. Shelley was to die in a boating
accident only a year after Keats, his body washing ashore with
a copy of Keats poems open in his pocket.
Keats works have endured the test of time. His Endymion
(A thing of beauty is a joy forever) and Ode on a Grecian Urn
(Beauty is truth, truth beauty) will no doubt remain popular
for years to come.
Figure 4. Keats grave in the Protestant Cemetery in Rome.

221
BLUE ZONES
Leaving Keats behind, we ew to Sardinia to experience
one of the so-called Blue Zones of longevity, popularized by
Dan Buettner, a National Geographic fellow, and his team of
researchers. They have identied at least ve areas around the
world where individuals have a multifold likelihood of living
to age 100 compared to most Americans. These Blue Zones
include 1) the Greek island of Ikaria, 2) the Nicoya Peninsula
of Costa Rica, 3) Loma Linda, California, 4) Okinawa, and 5)
Sardinia, the focus of our trip. A greeting in Sardinia is akea,
meaning may you live to 100.
Along with Dr. Ocie and Jo Ella Harris, friends from internship days, my wife, Marilyn, and I wanted to view personally
the lifestyle of the Sardinian inhabitants which enabled many
to remain active and vibrant well into old age. What did Dan
Buettner nd in his research and what did we observe in our
hiking trip with Classic Journeys?
In the Supramonte and Barbagia mountainous villages,
Buettners sta found 21 centenarians per 10,000 population, versus only 4 per 10,000 Americans. The men:women
ratio was about even, unlike in America where it is 1:4.
In the village of Perdasdefogu, nine living siblings in the
Melis family hold the Guinness world record of combined
age828 years.
In studying the lifestyles of the Sardinians, Buettner highlighted seven key ndings:
1. Their diet was lean, plant-based, with little meat.
2. They drank goats milk, which they felt might help combat
inammation.
3. Their family ties were strong.
4. They celebrated and cared for their elders.
5. They typically walked about 5 miles per day.
6. They drank several glasses of Cannonau red wine, believed
to be high in avonoids.
7. They had a sardonic sense of humor, laughing with and at
each other and themselves.
Missing from Buettners books was information on the
smoking habits in the Blue Zones (beyond the Seventh Day
Adventists from Loma Linda) and the results of blood pressure,
blood sugar, and lipid levels.
Our experience
We spent 3 nights in the Blue Zone area of Barbagia, in
the small hilltop town of Oliena, and drove cross-country to the
town of Silanus, in hopes of visiting a shepherd featured in the
Buettner publications. With the help of our guide, Fabricio,
who seemed to know everyone in town, we tried to visit several
extremely elderly shepherds. Two possibilities, both in their
mid-80s, were unavailable. One was high in the Supramonte
Mountains with his sheep and goats. The other was o at a
cattle auction.
We did enjoy meeting 93-year-old Francesca (Figure 5),
who was walking back from a shopping trip. Her grandson
was graduating from the medical school in Sassari, so the
grandmother and other family members were celebrating with
a dinner the next evening. Francesca had a sparkling person222
Figure 5. The author with 93-year-old Francesca.
ality, walked and stood erect, and showed a good recall for
recent and remote events, the latter including trips to Mexico,
Israel, and Egypt.
Our group hiked for nearly an hour up to a shepherds hut
and a view of the nearby Nuragic ruins (dating back over 3500
years). The shepherd, Giovanni, was 50 and took care of 100
sheep and 15 goats. His father, also a shepherd, had died of
throat cancer in his late 70s. Giovannis mother had adult-onset
diabetes but was otherwise in good health at age 88. Giovanni
had some central obesity, but otherwise seemed robust but at
risk for future diabetes.
We headed west, across Sardinia, passing through the Valley
of the Nuraghe. We stopped at the village of Silanus, in hopes
of meeting the shepherd, Tonino Tola. Our contact, who knew
him, stated he was now age 93. He gave us Toninos telephone
number. Our guide spoke with Toninos wife, who said he was
o working in the elds with his sheep and goats and would
be unable to meet with us. It seems that he had become sort of
famous since the publications, and multiple groups had sought
him out. One, from Japan, stayed all week and kept him from
his work, so his wife now protected him from outside interference. In any event, I was happy to learn that he was still not
only alive but thriving.
I made a list of Blue Zone foods and drinks (Figure 6) I
wanted to try:
Pasta
Pecorino cheese (from sheeps milk)
Fava beans
Chickpeas, zucchini, tomatoes, eggplant
Fennel
Milk thistle tea
Sourdough bread
Papassini cookies (with raisins, grape juice, almonds, and
fennel)
Local olive oils
Minestrone soup
We visited a home in Oliena to see how they made Carasau
bread (Figure 7), also known as shepherds bread. Shepherds
take it with them up high in the Supramonte Mountains, for
Volume 29, Number 2
Figure 7. Ladies in Oliena making Carasau bread, also known as shepherd's

bread.
In the Blue Zone area of Sardinia, we were able to sample the

food, especially the Cannonau wine, and view the active lifestyle
of the inhabitants. I found it both disappointing and amusing
that the few elderly shepherds we hoped to meet and to interview
were too busy to accommodate us, still tending their sheep and
goats in their 80s and early 90s, high in the mountains.
Acknowledgment
My thanks to Karen Galloway for preparing the manuscript
and to Stacie Waddell for gathering the gures.
Figure 6. A buffet of some Blue Zone foods.
it will provide nourishment for weeks at a time (washed down

with Cannonau wine).
SUMMARY
A trip to Italy enabled me to visit the small apartment in
Rome where John Keats spent his nal months and to visit his
grave in the Protestant Cemetery. I was only sorry that I was
unable to nd a nice bouquet of daisies to lay on his grave.
April 2016
SOURCES
Gittings R. John Keats, physician and poet. JAMA 1973;224(1):5155.
Cantwell JD. Six physicians and their common mistress. Atlanta Med 1994;68
6570.
John Keats. Wikipedia. Available at https://en.wikipedia.org/wiki/John_Keats;
accessed December 28 2015.
Buettner D. The Blue Zone. Washington, DC: National Geographic, 2008.
Buettner D. The Blue Zones Solution. Washington, DC: National Geographic,
2015.
223
Book Review
In Vitro Fertilization
Comes to America by
Howard W. Jones Jr.,
MD
Williamsburg, VA: Jamestown Bookworks, 2014.
234 pages, $11.99,
paperback.
Reviewed by Samuel P.
Marynick, MD
t is very exciting to
be present when
a major change
in the practice of
medicine occurs. It
is more exciting and
rewarding to be the
individual who is discovering and directing such a change.
Howard W. Jones Jr., MD, was such an individual.
In his book, In Vitro Fertilization Comes to America, Dr.
Jones chronicles the development of a new arena of medical
practice in North America. Medical care, by its very nature, is
constantly changing. On occasion a breakthrough occurs that
is revolutionary, and it takes medical care forward with greater
than a baby step. Such a change occurred in the practice of reproductive medicine in the timeframe between 1970 and 1990.
Several new disciplines made this leap possible. These included, not necessarily in order of importance (because they are
all important), the development of a radioimmunoassay that
allowed hormones to be accurately measured in small concentrations; the development of ultrasound to allow assessment
of follicular development and endometrial development; the
development of accurate gas sensing devices; the development
of incubators that could maintain near constant temperature,
humidity, and gas concentrations; and the development of tissue culture media that allowed for pre-embryo development
and other advances.
Howard Jones Jr. was a trained surgeon and surgical gynecologist. He was present for many discoveries made over the
last 80 years, as he lived to 104 years of age. Many of these
discoveries are chronicled in this volume.
This book is a brief recording of the events of Howard Jones
Jr.s life, and it details how he became interested in so many
different areas of medicine and medical care. It chronicles how
he met his wife Georgeanna in childhood, how he completed
his training, and how he became interested in human embryology, and it describes his unique relationship with Bob Edwards,
224
PhD, who is responsible for much of what we know about

human embryo development. Dr. Jones was a very humble
and thoughtful man, and this is evident in the humble way he
describes the events leading up to the birth of the first in vitro
fertilization (IVF) embryo transfer baby to be born in North
America.
Through this book, the reader is able to travel back in time
and experience the climate that was present when potential
human beings started being created outside of the body, in
vitro. It was not a time of peace and cooperation. Some individuals felt that egg fertilization outside of the body was to
be opposed, as it was too invasive. There was opposition that
was theologically and ethically based, and the opponents were
sometimes physical in their opposition. This led to somewhat
of a bunker mentality at Eastern Virginia Medical College in
Norfolk, Virginia, where this work was under way.
One chapter of the book deals with the Catholic Church and
its stance on assisted reproduction. The book includes the letter
that Howard Jones wife, Georgeanna, wrote to Pope John Paul
II. The letter explains and examines the many issues related to
the stance of the Catholic Church on assisted reproduction. I
will not spoil this unique insight, but will instead let you read
the volume to understand.
The next chapter discusses ethical issues related to human
IVF and reproduction, particularly the issue of personhood.
For the last 30 years of his life, Dr. Jones was deeply concerned
about ethical and legal issues and was an author or coauthor of
books regarding these subjects (Legal Conceptions: The Evolving
Law and Policy of Assisted Reproduction Technologies, with S. L.
Crockin, Johns Hopkins University Press, 2009; Personhood
RevisitedReproductive Technology, Bioethics, Religion and the
Law, Langdon Street Press, 2013).
One item that is not covered in this book is how generous
Dr. Jones and his staff were to visiting scientists. They gladly accepted visitors from all over the world to help them understand
the process by which human life could be created in vitro. The
first time I personally visited the Jones Institute in Norfolk was
in 1986. Security was present. Different areas of the reproductive center at the institute had doors mislabeled to throw off
curious outsiders. For example, the embryology laboratory had
a door label that said Soiled Linen.
The foreword to this volume was written by Ms. Elizabeth
Carr, the fi rst IVF individual born from this technology
in America. Ms. Carr and Dr. Jones had a relationship of
34 years that spanned from her birth until Dr. Jones untimely death. I had the pleasure of visiting with Ms. Carr at
the annual meeting of the American Society for Reproductive
Medicine in the fall of 2015 (Figure). Ms. Carr told me that
Dr. Jones nearly always attended her birthday party, and from
her birth on he prepared her to manage the publicity that

came with being the first IVF baby in America. Ms. Carr had
many touching stories about how Dr. Jones had positively
influenced her life.
The final chapter relates to how this science has changed
the practice of reproductive medicine. Prior to IVF, a couple
coming to a fertility specialist had around a 50% chance
of having a child. Now the chance of being successful
approaches 100%.
Anyone interested in contemporary medicine, philosophy, law, reproductive medicine, and the history of medicine in general will benefit from reading this work. I am so
delighted that this humble man, Howard W. Jones Jr., MD,
took time at the age of 103 to complete this enlightening
project.
The reviewer, Samuel P. Marynick, MD, is medical director of the Texas
Center for Reproductive Health in Dallas, Texas.
Figure 1. Dr. Marynick with Elizabeth Carr, the first individual born through in
vitro fertilization in America.
April 2016
Book review
225
Reader comments
HEARTS CONSIDERED FOR TRANSPLANTATION AND
TAKOTSUBO SYNDROME
read with interest the report by Ravi et al, in the January
2016 issue of Proceedings, about the successful transplantation of the heart of a 17-year-old woman to a 61-year-old
man with end-stage ischemic cardiomyopathy (1) and the
accompanying thoughtful commentary by Lima (2). The authors referred to the currently prevailing restrictive approach
in considering donor hearts for procurement for cardiac transplantation (3) and stated that to date, there are no reports of
takotsubo syndrome (TS) in the context of cardiac transplantation (1). In fact, several such cases have been published and
discussed in the literature (47). Indeed, a similarity has been
suspected to be present in donor hearts of resuscitated cardiac
arrest victims, patients with neurogenic stress cardiomyopathy,
and patients with TS (6). Accordingly, it is relevant to ask the
authors about other triggering or inciting TS factors beyond
the motor vehicle accident, like the use of catecholamines (6,
7), in the clinical management of this unfortunate 17-year-old
girl. A lesson should be to proceed with procurement of donors hearts for cardiac transplantation when underlying heart
disease in the potential donors is unlikely. Also, we should start
using echocardiography serially and frequently during the clinical management of potential donors, and we should consider
emphasizing mechanical devicebased hemodynamic support
while deemphasizing use of catecholamines (6, 7).
John E. Madias, MD
Icahn School of Medicine at Mount Sinai
New York, NY
E-mail: madiasj@nychhc.org
1.
2.
3.
4.
5.
6.
7.
226
Ravi Y, Campagna R, Rosas PC, Essa E, Hasan AK, Higgins RS, Emani
S, Sai-Sudhakar CB. Successful heart transplantation using a donor
heart aicted by takotsubo cardiomyopathy. Proc (Bayl Univ Med Cent)
2016;29(1):7374.
Lima B. Using broken hearts for cardiac transplantation: a risky venture
or fruitful endeavor? Proc (Bayl Univ Med Cent) 2016;29(1):7475.
Taylor DO, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Rahmel AO, Kucheryavaya AY, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fth ocial adult heart
transplant report2008. J Heart Lung Transplant 2008;27(9):943956.
Guglin M, Novotorova I. Neurogenic stunned myocardium and takotsubo
cardiomyopathy are the same syndrome: a pooled analysis. Congest Heart
Fail 2011;17(3):127132.
Guglin M. How to increase the utilization of donor hearts? Heart Fail
Rev 2015;20(1):95105.
Madias JE. Neurogenic stress cardiomyopathy in heart donors is a form
of takotsubo syndrome. Int J Cardiol 2015;184:612613.
Madias JE. Donor hearts, hearts of resuscitated cardiac arrest victims,
hearts of patients with neurogenic stress cardiomyopathy, and hearts
of patients with takotsubo syndrome: any commonalities? Int J Cardiol
2015;199:33.
I enjoyed reading the interesting case report recently published by Ravi et al (1). The authors have described a successful
heart transplantation using the heart of a 17-year-old girl involved in a motor vehicle accident. Echocardiography revealed
apical ballooning of the left ventricle consistent with takotsubo
syndrome (TS). The left ventricular apical ballooning was also
directly observed at procurement. One striking nding is the
very rapid resolution (within hours after donor cardiectomy) of
the left ventricular dysfunction. It occurred after the completion
of heart transplantation, where intraoperative echocardiogram
revealed complete resolution of the left ventricular ballooning.
Could the resolution have occurred directly after donor cardiectomy before transplantation? The disease resolved in spite of
continued inotropic support during the rst 48 hours.
It is justiable to wonder whether this rapid recovery has
to do with the simultaneous surgical sympathectomy during
donor cardiectomy. Surgical sympathectomy may have resulted
in relief of the apical myocardial cramp (stunning) caused by
the brain deathinduced disinhibited cardiac sympathetic tone.
If this is true, this observation strengthens the hypothesis about
the involvement of the local cardiac sympathetic overactivation
disruption in the pathogenesis of TS. The authors have appropriately stated that a loss of brainstem parasympathetic outow/
disinhibition of sympathetic tone may occur in brain death
induced TS. Actually, there is substantial evidence supporting
the hypothesis that the local cardiac sympathetic overactivation
disruption with norepinephrine seethe and spillover is causing
TS, as has been discussed in detail elsewhere (2).
The authors directly observed the apical ballooning at procurement; I wonder if this observation was done before or after
donor cardiectomy. If it was before, could the authors observe
any change in the apical ballooning after cardiectomy? Furthermore, could the authors describe the palpation ndings of the
ballooned apical region and the remainder of the left ventricle if
palpation of the left ventricle was done? Endomyocardial biopsy
was done 1 week after heart transplantation. Have the authors
tried to take biopsies from the apical region? If so, did they nd
signs of contraction bands and vacuolization, which characterize
the histopathological ndings of TS, or did they nd signs of
complete healing of the disease (TS) histopathologically?
Transplantation of donor hearts aicted with TS opens an
excellent opportunity for research into the pathogenesis of TS.
This author recommends that the heart transplantation team
rst inspect and palpate the left ventricle followed by surgical
sympathectomy of the heart and then inspect and palpate the
left ventricle again before donor cardiectomy and repeat the
same procedure during completion of the heart transplantation, with intraoperative echocardiography, as the authors of
the current case have appropriately done. The analysis of the
biopsy for TS changes in addition to rejection changes is also

highly recommended.
Shams Y-Hassan, MD
Karolinska University Hospital
Stockholm, Sweden
E-mail: shams.younis-hassan@karolinska.se
1.
2.
Ravi Y, Campagna R, Rosas PC, Essa E, Hasan AK, Higgins RS, Emani
S, Sai-Sudhakar CB. Successful heart transplantation using a donor
heart aicted by takotsubo cardiomyopathy. Proc (Bayl Univ Med Cent)
2016;29(1):7374.
Y-Hassan S. Acute cardiac sympathetic disruption in the pathogenesis
of the takotsubo syndrome: a systematic review of the literature to date.
Cardiovasc Revasc Med 2014;15(1):3542.
The authors respond

We thank Dr. Madias for his comments and acknowledge
the presence of other reports pertaining to this topic. It is certainly possible that the use of catecholamines following the
motor vehicle accident could have potentially caused the development of takotsubo syndrome, and we agree with Dr. Madias comments on serial echocardiography in the assessment
of potential donors with such a presentation and the use of
mechanical devicebased hemodynamic support.
We thank Dr. Y-Hassan for his comments. It is conceivable
that the surgical sympathectomy secondary to donor cardiectomy could have resulted in the resolution of the apical ballooning. At procurement, the apex was felt to be normal, did
not appear to be thinned out following cardioplegic arrest, and
was comparable to the rest of the left ventricle. A biopsy was
not performed on the left ventricular wall at the apex. We agree
with Dr. Y-Hassan that detailed evaluation in the perioperative
period is important to monitor the progress and improvement
of the syndrome.
Yazhini Ravi, MD
Division of Cardiothoracic Surgery
Baylor Scott & White Healthcare, Temple, Texas
E-mail: yravi@SW.org
ELECTRONIC MEDICAL RECORDS

Dr. Couch's commentary (1) in the January 2016 issue of
Proceedings on the electronic health record (EHR) is correct.
However, it fails to mention the full cost of the EHR in terms
of the loss of physician productivity. For example, Dallas Diagnostic Association experienced the premature retirement of 12
physicians in large part due to the adverse impact of the EHR.
No one at HealthTexas Provider Network did exit interviews
with these physicians. Almost all of the currently practicing
physicians at Dallas Diagnostic Association have reported decreased productivity and decreased satisfaction with the practice
of medicine due to the burdens imposed by the EHR. Certainly,
the economics of the practice of internal medicine also play a
signicant role in the dissatisfaction of internists and internal medicine subspecialists with their professions. It is hoped
that you and your colleagues will be eective in improving the
April 2016
usability of the EHR to enhance the experience of both patients

and providers.
Lannie Hughes, MD
1.
Couch C. Invited commentary to Surgeons perspective of a newly initiated electronic medical record. Proc (Bayl Univ Med Cent) 2016;29(1):23.
FACTS AND IDEAS

Regarding the January Facts and ideas comment on health
care savings accounts and high-deductible plans, do you know
if the requirements for lower deductibles came from the legislation or the regs? Very nice article. Thank you again. I
practically tear open the journal to get to the Facts and ideas
from anywhere.
One of my thoughtful friends (our mayor, an attorney; we
serve together on our LaGrange City Council) felt that people
who can analyze their costs and reduce costs self-select into
higher-deductible plans. He felt it was not truly because of the
eect of the deductible itself. I thought that was a very good idea.
Im not sure if there is data to answer the question either way.
Tom Gore, MD
LaGrange, Georgia
I always enjoy your Facts and Ideas comments, but especially
the review of David McCullough's book Americans in Paris. I
had him autograph my copy when it rst came out. Mason
Warren comes from a long line of surgeons which continued
into the 20th century. I have read his letters in The Parisian
Education of an American Surgeon published some time ago by
the American Philosophical Society. You might enjoy it as well,
or perhaps youve read it.
Jeanie Woods
Waynesboro, Pennsylvania
CUBA
I really did enjoy reading your article on the trip to Cuba
that you made in February 2015 (1). As best I can tell, not much
has changed in Cuba from 2001 to 2015.
I have never recorded the experience that my wife and I had
in 2001 when we accompanied the Haverford College baseball
team and students for a 2-week daily baseball trip and cultural
exchange in Cuba. Our oldest son, Laird, played baseball for
Haverford. My wife and I served as the doctor and nurse for
the Haverford delegation.
We were required to enter Cuba from Jamaica. Therefore,
we ew from Philadelphia to Montego Bay and then returned
to Havana. During the time we were ying from Philadelphia
to Montego Bay, Cuban aircraft shot down two airplanes from
the US that were dropping leaets over Cuba.
Prior to our arrival in Cuba, baseball games and meetings had been prearranged. When we arrived in Havana, the
delegation was informed that, because of the incident regarding
the American airplanes, all previously arranged games and meetings were canceled. These prearranged baseball games were to
be the spring training for the Haverford baseball team.
Reader comments
227
The Haverford delegation was

given two tourist buses for transportation. During the ride from the
airport to our hotel, we learned from
our bus driver, a former professional
baseball player, that it was possible
to nd baseball games in Cuba 247-365. We would just need permission to leave Havana and drive into
the country and nd a city team for
a game.
The next day we had permission
to leave the city to tour the country.
Our bus driver headed straight for
Santa Clara (about 50 miles west of
Havana). There, at the base of some
signicant mountains, was a beautiful baseball eld. The mountains
were the backdrop looking out from Figure 1. The Haverford team playing in Cuba.
home plate. The word went out that
The Haverford College team gave the retired Cuban Nationa ball game was to be played that day. It required a couple of
als, most of whom had gray hair, a good game and won the game
hours for the Santa Clara team to be in position to start the
9 to 7. The Haverford team was able to beat the level III team
game. During that time, the Haverford team took batting practwice, and they split the games with the level II team. Playing
tice and elding practice.
against the level I team and the Reforma Plaza team were like
It was quite something to see young men walking up in their
playing the New York Yankees. The Reforma Plaza team had a
civilian clothes and work boots, some knee-high rubber work
player that was the spirit and image of the Ranger's slugger Juan
boots, and changing into uniforms and putting on their cleats.
Gonzalez. This gentleman hit a couple of moon-shots out of
The children of the town, mainly young boys, were all over the
the Reforma Plaza Park. The score was not pretty: 14 to 2. The
Haverford dugout. The game was played, and it was very comfour games played against the medical school team were split.
petitive. I cannot remember who won the game, but the score
I was able to visit with many of the medical student baseball
was close. As the Haverford team was loading its equipment,
players. This was quite rewarding.
it was discovered that signicant numbers of gloves, bats, and
The hotel we stayed in, the Ambos Mundos, was where
balls were missing. After the game, the children of Santa Clara
Ernest Hemingway lived before he purchased his estate. As
disappeared quickly. This led to the realization that no one could
we stayed in this hotel 2 weeks, we got to know the personnel
be allowed in the dugout from the community where the team
fairly well. When the workers at the hotel learned that I was a
was playing. Following this game, the team had a wonderful
physician, I saw several of the hotel employees who had quesmeal at a restaurant beside the natural waterfall in the mountains
tions about their medical problems. The main conditions that
that were the backdrop for the baseball eld.
I treated during the trip were bug bites and sprains. The Ambos
On the road back to Havana, the bus driver started thinking
Mundos Hotel had bedbugs. Insect repellent works wonderfully
of how to play games against other teams. He mentioned that
to prevent bedbug bites. You need to get a good coating of insect
Cuba had an athletic training complex. At this complex was
repellent before retiring for the evening.
training for all the Olympic sports, with a wonderful baseball
The day before our return to the US, the lady who had cared
stadium and baseball teams of several levels of expertise. The
for our room at Ambos Mundos said to Sharon and me, Would
bus driver detoured to the facility, and the director of athletics
you like to see Mr. Hemingway's room? We answered that we
at Haverford College, Mr. Greg Kannerstein, discussed playing
would, and we walked up a stairwell to the third oor of the
games against the various level baseball teams at the academy.
hotel. This lady opened the door and a room was revealed that
Contests were set for the next several days (Figure 1). The
had a single bed, a nightstand, and a small desk on which sat
rst game would be played against a group of retired Cuban
a Royal typewriter, human powered. There was blank typing
national players in the main stadium of the facility. This would
paper on the desk. The Ambos Mundos has not touched this
be followed by daily games against the level III players, the
room except to clean it since Mr. Hemingway left the hotel in
level II players, and then the level I players. The team was
the 1950s.
set to play Fidel Castro's personal team, the Reforma Plaza
When we were in Cuba, there were policemen every half
team, at the baseball eld adjacent to Reforma Plaza. Also,
block. The city was not safe. We were counseled to not walk by
since every professional school in Cuba has a baseball team,
ourselves and to take taxis when possible. The only problematic
several games were scheduled against the medical school team
time of the trip came the night we went to the national stadium
from Havana.
228
Volume 29, Number 2
to watch two professional teams play a game. The two teams

were from Havana and a city in eastern Cuba (I do not remember the name of the city). During the game, I was fortunate
to be able to purchase a locally made baseball bat from one of
the players on the visiting team. I cannot recall how much the
purchase price was. The bat was quite heavy. A dollar bill went
a long way in Cuba in 2001.
The ballgame went into extra innings and did not nish
until after midnight. As it was a very good game, we stayed to
watch. When we exited the stadium, there were no taxis to be
seen. The policeman at the stadium entrance spoke pretty good
English and explained that we would need to walk several blocks
to the closest all-night taxi stand. He took a piece of paper and
drew a map for us. As there was no ability to use credit or debit
cards in Cuba in 2001, Mr. Kannerstein had several thousand
dollars in a satchel which he carried everywhere on his person
to pay bills as they materialized.
We were a ways from the stadium when three young men
and two boys started to follow us. They taunted us and then
produced knives and demanded Mr. Kannerstein's satchel. Mr.
Kannerstein told the young men that they would not get his
satchel and they needed to leave. By this time, we could see
the taxi station about a half block away. I told Kannerstein to
make a run for it and I would use my baseball bat to retard these
young thugs. Kannerstein took o running with his satchel, and
I loaded my bat and was ready to swing. A miracle occurred.
The young fellows with the knives ran. I start running to catch
up with Kannerstein. We got our taxi and went back to the
Ambos Mundos.
The next to last day in Cuba, the Haverford baseball team
played the hotel team from the Ambos Mundos. The pitcher for
the Ambos Mundos team was a former National Team player for
Cuba. He was close to 50 years old, I would guess, and was a lefty.
He had a younger brother in the US pitching for the New York
Yankees. Following the game, as the players were visiting, my
oldest son, Laird, observed that he and this pitcher had similar
size feet. The pitcher's shoes were not in good condition and
were patched together. Laird had a spare pair of baseball shoes
in his bag. He took the pair of shoes out of his bag and asked
this gentleman if they would t, and they did. The gentleman
took o his Cuban National jersey and gave it to Laird. I am sure
Laird still has that jersey. One of my favorite pictures is of Laird
pitching in the Cuba jersey during a practice game the Haverford
team had the next day prior to the plane ride home (Figure 2).
There was so much more to this trip than I have recorded,
but I would agree with you that Cuba and the United States of
April 2016
Figure 2. Laird Marynick pitching a game in Cuba.
America will be best served by exchange rather than isolation.

I could discuss politics, philosophy, and economics. To do so
only upsets most people because they have an opinion and
their opinion is correct. They cant comprehend how anyone
with half of a brain could have a dierent point of view. It is
a human failing that we believe individuals who do not agree
with us are always wrong. Sometimes, there is more than one
correct answer for the same question, sometimes not. However,
history shows us that certain policies generally work better than
others over time. Communism has shown that it is a recipe for
economic and cultural failure. From the Pilgrims to Cuba, the
result is the same.
Samuel P. Marynick, MD
Texas Center for Reproductive Health
Dallas, Texas
1.
Roberts WC. A week in Havana, Cuba, in February 2015. Proc (Bayl Univ
Med Cent) 2015;28(4):538540.
Reader comments
229
From the Editor
Facts and ideas from anywhere
COSTS OF DRUGS
IN THE USA VERSUS
OTHER COUNTRIES
Norway, one of the
worlds richest economies, is an expensive
place to live (1). A Big
Mac costs $5.65; a gallon of gasoline, $6.00. In
2015, a vial of the cancer
drug Rituxan, however,
cost Norways taxpayerfunded health system
$1527, while the US
William C. Roberts, MD.
Medicare program paid
$3678; an injection of the asthma drug Xolair cost Norway
$463, 46% less than what Medicare paid for it.
Drug prices in the US usually are shrouded in mystery,
obscured by condential rebates, multiple middlemen, and the
strict guarding of trade secrets. But for certain drugsthose
paid for by Medicare Part Bprices are public. By stacking
these Medicare prices against pricing in three foreign health
systems, The Wall Street Journal was able to determine drug cost
dierences in several countries and what lies behind them. The
US prices were higher for 93% of 40 top-branded drugs available in both Norway and the USA in 2015. Similar patterns
appeared when US prices were compared with those in the UK
and Canada. Throughout the developed world, branded prescription drugs are generally less expensive in non-US countries
than in the USA.
The state-run health systems in Norway and in many other
developed countries drive hard bargains with drug companies:
setting price caps, demanding proof of a new drugs value in
comparison to existing ones, and sometimes refusing to cover
medicines they doubt are worth the cost. The governments
health systems also are the only large drug buyers in most of
these countries, giving them substantial negotiating power. The
US market, by contrast, is highly fragmented, with bill-payers
ranging from employers to insurance companies to federal and
state governments.
Medicare, the largest single US payer for prescription
drugs, is by law prevented from negotiating prices. For Medi230
care Part B, companies report the average price for which they
sell medicines to distributors. By law, Medicare adds 6% to
these prices. Beneciaries are responsible for 20% of the costs.
The arrangement means that Medicare essentially forfeits its
buying power. In the US, few payers, public or private, cite
cost as a reason to deny drug coverage. Medicare Part B typically covers drugs and services deemed reasonable and necessary. If it is a Food and Drug Administration (FDA)-approved
drug and prescribed by a duly licensed physician, Medicare
will usually cover it.
The pharmaceutical industry says controls, such as those
seen in Europe, discourage investment in research and deny
patients access to some drugs. If US pricing fell to European
levels, the industry would almost certainly cut its research
and development spending. The higher US prices also help
drug makers aord hefty marketing budgets that in the US
include consumer advertising, something Europe does not
allow. Pharmaceutical and biotechnology companies in the
US earn an average net prot of 16%, compared with an
average of about 7% for all companies in the Standard &
Poor 1500 Index.
Norway had a gross domestic product per capita of $97,000
in 2015 vs. $55,000 in the USA. In Norway, the state pays for
most prescription drugs, although patients pay for some used
for short periods. The government controls costs in part by
setting maximum prices. To do that, it reviews prices in nine
neighboring countries and takes the average of the three lowest.
The Norwegian Medicines Agency then reviews patient data to
decide whether a new drug is cost-eective. The drug maker
must request a reimbursement price at or under the maximum
that Norway has set and submit a detailed comparison of the
drugs costs and benets vs. existing treatments. Norway recommends that companies describe a drugs cost per quality-adjusted
life year, a gauge used by many government health systems.
Medicare is barred from using this gauge as a threshold in determining coverage. Drug companies know that Norway will
sometimes deny coverage, and this threat is often enough to get
them to oer a discount.
The UK sometimes controls prices by capping the level
of National Health Service spending on drugs each year
and requiring the pharmaceutical industry to reimburse the
National Health Service for any spending over those limits.
Of 40 branded drugs covered by Medicare Part B and also available in the UK in 2015, 98% were more expensive in the USA.
Canada does not have a single large pharmaceutical payer,
but drug prices are substantially lower than in the USA, held in
check by regulation. Its federal agency, the Patented Medicine
Prices Review Board, sets a maximum price for new drugs, based
on their therapeutic benets and the prices in six European
countries and the USA. Once a drugs maximum price is set, the
maker cant raise prices faster than the national ination rate or
above the highest price in the seven other countries.
Countries with national health systems tend to feel they
cannot aord everything for everybody at any price. That is not
the health philosophy in the USA.
FLU SHOTS FOR HOSPITAL WORKERS
Drs. M. Todd Greene and Sanjay Saint of the Veterans Administration Ann Arbor Healthcare System had a piece in The
Wall Street Journal indicating that seasonal u caused as many
as 55,000 deaths in 2014 according to the Centers for Disease
Control and Prevention (CDC) (2). Some of these deaths almost
certainly were the result of health care workers transmitting the
inuenza virus to patients. Some hospitals began requiring their
sta to get vaccinated or wear masks if they could not or would
not get vaccinated. A CDC survey in late 2015 showed that
hospitals, physicians oces, long-term care facilities, and other
clinics with mandatory vaccinations achieved 96% coverage
for their workers compared with 44% coverage in institutions
without mandatory vaccinations. A 2014 CDC study showed
that health care worker vaccinations reduced patients risk of
inuenza-like illness by just over 40%.
The CDC has long recommended annual inuenza vaccinations for all health care personnel. The US Department of
Health and Human Services wants 90% of health care workers
vaccinated by 2020. The US, however, appears to be a long
way from reaching that goal. Now, only about 43% of the 386
responding nonfederal hospitals require health care personnel
to be vaccinated against the u. Only 1% of the 77 Department
of Veterans Aairs hospitals that answered the survey required
health care personnel to get u vaccinations! Mandates that
allow exemptions for religious or health reasons and require
unvaccinated workers to use masks can protect both patients
and workers rights.
In September 2015, Kaiser Permanente, the giant managed care organization, came to an agreement with a coalition
of unions representing 105,000 health care workers, including nurses, medical assistants, custodial maintenance and food
service workers, lab technicians, scientists, and clerical sta, to
either receive the annual u vaccine or wear a surgical mask
while providing patient care during the u season. Other public
unions need to get on board.
The Department of Veterans Aairs is considering a proposal
to mandate inuenza vaccinations for health care workers. It
needs to adopt the proposal now. Veterans Aairs is the largest
health care system in the US and one of the largest in the world.
If it and its unions agree to mandatory vaccinations, that would
send a strong message to the rest of the health care industry.
April 2016
ZIKA VIRUS
The Zika virus, a mosquito-borne infection, has already
spread to numerous countries and territories in the Americas
(3). It poses particular danger to pregnant women. The virus is
linked to an outbreak of birth defects in Brazil. It has spread to
the USA and to every country in the Western Hemisphere where
the Aedes mosquitos are known to live. International travel, of
course, will help the virus spread quickly. Zika does not spread
from person to person, but people infected while traveling can
spread the virus in the USA if they are bitten by local mosquitos
which then may spread the infection here. The CDC has issued
a travel alert warning pregnant women to avoid travel to the
countries where Zika is present. Fortunately, the condition in
nonpregnant adults is usually quite mild.
CONCUSSIONS IN THE NATIONAL FOOTBALL LEAGUE
According to the National Football League, there were 182
reported concussions from the 2015 regular season games, 58%
more than the 115 in 2014, 148 in 2013, and 173 in 2012 (4).
Among the possible explanations for the increase was a doubling
in the number of players screened for possible concussions.
Surely, not all concussions are equal. There must be small ones
that are not noticed by anyone or realized by the player. The
longer one plays in the National Football League, the greater
the acquisition of concussions.
MAJOR ORTHOPEDICS PROCEDURES PERFORMED AT RURAL
CRITICAL-ACCESS HOSPITALS
The Wall Street Journal in December 2015 reported its investigation of major orthopedic surgeries at small rural hospitals
(5). It found that inpatient joint replacement operations covered
by Medicare rose 43% at the critical-access hospitals from 2008
to 2013, far outpacing the 9% growth of those services at general
hospitals. The trend reects nancial incentives built into the
way Medicare pays the nations roughly 1300 critical-access hospitals, generally isolated facilities with 25 or fewer beds. Many
studies show that patients generally get better results when their
procedures are done at hospitals that perform them frequently.
The average critical-access hospital performing inpatient joint
replacements in 2013 did about 26 that year compared with
about 130 at general hospitals. Hospitals doing >100 procedures
a year have the lowest risks. The risk-adjusted rate of 30-day
mortality per 1000 patients was 5.0 at general hospitals but 9.0
at critical-access hospitals. Critical-access hospitals are exempt
from federal rules that require most facilities to report quality
measures, such as rate of surgical complications!
SCHOLARSHIP AND LIFE EXPECTANCY
Scott Burns of The Dallas Morning News was one of the 837
graduates of the Massachusetts Institute of Technology in 1962
(6). He found that only 126 of his classmates were known to
be dead, producing a survival of well over 80%, a rate much
better than that of the broad US population. According to US
life tables, only 62% of all men alive at age 22 survive to age
75. He opined that if the survival rate of his class of 1962 continues on its current path, life expectancy for the class would be
231
92 years. He indicated that the survival of the more educated

is greater than that of the less educated. According to Social
Security actuaries, the top half of the Social Security wage base
can expect to live nearly 5 years longer than the bottom half.
Those in the top 10% of the wage base can expect to live about
10 years longer than the bottom 10%. In 2015, Nobel laureate
Augers Deaton and his wife, Anne Case, published an article
showing that life expectancy for less educated, lower-income
white men and women had actually declined by 5 years. The
life expectancy of white women without a high school diploma
was only 73.5 years; the life expectancy for white men without a
high school diploma was 67.5 years. Study hard and live longer!
UPGRADING PHYSICAL ACTIVITY
Berra and colleagues (7) made the case that physical activity
counseling should be upgraded to the equivalent of vital signs.
The reason of course is that there is overwhelming evidence that
regular physical activity is one of the most powerful healthpromoting practices that people can do. For decades, research
has shown that regular physical activity protects against major
chronic diseases including systemic hypertension, type II diabetes mellitus, obesity, heart disease, stroke, cognitive decline,
select cancers, and depression. No other single intervention or
treatment is associated with such a diverse array of benets.
In a recent call to action for the National Physical Activity Plan of the American Heart Association, a lack of physical
activity was highlighted as a leading cause of death worldwide.
The report emphasized that advice from health professionals
signicantly inuences adoption of healthy lifestyle behaviors,
including regular physical activity, and can increase satisfaction
with medical care.
Given the overwhelming evidence of benets from physical
activity and the vital role of health professionals in motivating
behavior change, the lack of physical activity counseling in the
clinical setting represents a lost opportunity to improve the
health and well-being of patients, and with minimal costs. In
2012, there were >506 million primary care visits in the USA,
most of which were for prevention and treatment of preventable
chronic health conditions. Yet, only 34% of adults reported
being counseled about physical activity at their last physician
visit. Even among adults with prediabetes and other vascular
risk factors, only 40% reported receiving such counseling.
Technology, of course, provides numerous ways to improve
the adoption of health promotion behaviors. The TEXTME
study randomized 810 adults with coronary artery disease to
receive or not receive motivational and informational text
messages related to physical activity, diet, and smoking cessation. At 6 months, the investigators found improvements in
all of the above outcomes as well as blood pressure and body
mass index in the active message group compared with the
control group.
Clinicians can recommend pedometers or other wearable
measurement devices, have resources available at the oce visit
(such as self-monitoring forms and reminders), and provide
patients with a list of selected apps and websites to encourage physical activity. Because physicians and other health care
232
professionals are trusted sources of health information and can

help patients set priorities for improving their health, physical
activity counseling aords a vitally important opportunity to
improve patients health and well-being.
PETER MARK ROGET, MD, AND HIS THESAURUS
Rogets Thesaurus of English Words and Phrases rst appeared
in June 1852 and subsequently has emerged as one of the most
recognizable books in the English language (8). The book
has sold nearly 40 million copies. Although almost everyone
is familiar with his book, few people know anything about
Peter Mark Roget (17791869), the eminent 19th century
polymathphysician, physiologist, mathematician, inventor,
writer, editor, and chess whizand what motivated him to
write this immortal book.
Roget was obsessed with words ever since he began studying Latin as a schoolboy. Roget completed a rst draft of the
Thesaurus (the Latin word for treasure or treasury) in 1805
when he was 26 years old and working as a physician in Manchester, England. It was not until his retirement from medical
practice, however, in 1848 at the age of 69 that Roget set out
to nish the Thesaurus. The still spry Roget worked nonstop
for nearly 4 years to complete the book. He tinkered with his
masterpiece until his death at age 90, having watched over the
publication of 28 editions.
Rogets Thesaurus of English Words and Phrases classied
and arranged ideas so as to facilitate writers. He put both a
book of synonyms and a topical dictionary (a compendium of
thematically arranged concepts) under one cover. Borrowing
the principles of zoological classication, Roget organized all
knowledge, not just words. Just as his hero, the 18th century
naturalist Carl Linnaeus, divided animals into six classes, Roget
divided his 1000 concepts as follows: 1) abstract relations, 2)
space, 3) matter, 4) intellect, 5) volition, and 6) aections. The
1000 headings of the 1852 edition, from which are culled the
epigraphs to each chapter in the book, were arranged not alphabetically but according to where a given idea t within Rogets
classication system. In that edition, the rst entry is existence,
which falls under the rst class abstract relations. The purpose
of the classication was to help readers nd the right word for a
given idea. Shortly before publication, Roget decided to insert
an alphabetical index as an appendix, thus enabling readers to
use the Thesaurus as a conventional book of synonyms.
Scholars immediately began fawning over his prodigious
eorts. One reviewer stated, Roget will rank with Samuel
Johnson as a literary instrument-maker of the rst-class.
Generations of British writers would thereafter look up to
Roget as a kindred soul who could oer both emotional and
intellectual substance.
An American version of the Thesaurus appeared in 1854
and initially appealed mainly to scholars. The crossword puzzle
craze of the 1920s, however, turned Roget into a celebrity in
the US as well as in the UK. In February 1925, The New York
Times magazine described Roget as Saint of Crosswordia. In
the days before every laptop became equipped with a thesaurus,
Roget had a market all to himself and was an icon.
Volume 29, Number 2
Rogets new world of 1000 concepts was not only his monumental gift to posterity, it was, rst and foremost, the primary
means by which he preserved his own sanity. Overwhelmed by
the early death of his father and the emotional instability of
his mother, Roget was constantly burying himself in books to
cope with his sadness, anxiety, and anger. As a boy Roget kept
dreaming up new worlds in the hope of escaping the dreary
one in which he found himself. Commenting on his embrace
of astronomy when he was 12, his mother remarked, Peter
ever eager after new studies, has for this while left this world
and lived wholly in the starry regions. Madness ran in the
immediate family. Rogets maternal grandmother, Margaret
Garnault Romily, who suered from an unidentied mental
disorder thought to be severe depression or schizophrenia, was
in an almost vegetative state for most of her life. In his memoir
published in 1840, Rogets uncle, the distinguished member of
Parliament Sir Samuel Romily, mentioned that she had a nervous collapse when her parents initially objected to her marriage
to his father. Romily also revealed that he and his two siblings,
Thomas and Catherine (Peters mother), were raised jointly by
an aunt, Margaret Facquier, and a nurse, Mary Evans, adding
that as far as my mother, she was incapable, from the bad state
of her health, of taking any part in our education. Romily
himself committed suicide at the age of 61, at which time Rogets mother, until then merely temperamental and emotionally
demanding, lapsed into paranoia. For the last 15 years of her
life, Catherine Romily Roget engaged in increasingly bizarre
behavior. She lived her later years with her sister, Annette, who,
like her mother, suered frequent bouts of depression. Rogets
daughter, Kate, followed a similar trajectory.
Roget himself was not immune, as his uncle once wrote
him, Despondency is, I have always thought, the great defect
of our family, and I do not think that you are more exempt from
it than the rest. Described at 14 by his mother as awkwardly
bashful, the young Roget was slow to make friends and felt
most comfortable in his own company. Unlike his mother or
his uncle, however, Roget managed to stave o madness. As a
boy he stumbled upon a remarkable recoverythat compiling
lists of words could provide solace, no matter what misfortunes
might befall him. He was particularly fond of cataloguing the
objects, both animate and inanimate, in his environment. As
an adult he kept returning to the classication of words and
concepts. Emerging in the nuances of language invariably both
energized him and kept his persistent anxiety at bay.
As he grew older, though he had satisfying relationships
with both his wife, Mary, and the governess, Margaret Spowers,
who became his unocial second wife after Marys early death,
Roget remained more interested in words than in people. After
he had published his Thesaurus, Roget stated, Men are odd
animals; I have never felt as at home around them as around
their words; without these, theyre monkeys. The other day I
was going through my book and it struck me that I have more
words for disapprobation than approbation. Why is this?
Over the course of his scientic career, Roget would specialize in physiology, and in 1834 he published the two-volume
Animal and Vegetable Physiology: Considered with Reference to
April 2016
Figure. Stamp issued by Belgium to commemorate the centenary of the death

of Adolphe Quetelet (17961874), who in 1832 developed the Quetelet Index,
now known as the body mass index.
Natural Theology, also known as his Bridgewater Treatise. This

work, held in highest esteem by 19th century academics, consisted of nothing but a catalog of specic plants and animals.
ADOLPHE QUETELET AND BODY MASS INDEX
The quest for a practical index of relative body weight began shortly after actuaries reported the increased mortality for
their overweight policyholders after World War II, when the
relation between weight and cardiovascular disease became the
subject of epidemiological studies (9). It became evident then
that the best index was the ratio of the body weight in kilograms
divided by the square of the height in meters, or the Quetelet
Index, described in 1832 by Adolphe Quetelet (17961874)
(Figure). He was a Belgium mathematician, astronomer, and
statistician who developed a passionate interest in probability
calculus that he applied to study human physical characteristics
and social aptitudes. His pioneering cross-sectional studies of
human growth led him to conclude that other than the spurts
of growth after birth and during puberty, the weight increases
as the square of the height, known as the Quetelet Index, until it was termed the body mass index in 1972 by Ancil Keys
(19042004). For his application of comparative statistics to
social conditions and moral issues, Quetelet is considered a
founder of the social sciences. His principal work, A Treatise of
Man and the Development of His Facilities, published in 1835,
is considered one of the greatest books of the 19th century. A
tireless promoter of statistical data collection, Quetelet organized in 1853 the rst International Statistical Congress, which
launched the development of a uniform nomenclature of the
causes of death applicable to all countries, the progenitor of the
current International Classication of Diseases.
HEALTH RANKINGS OF TEXAS
In Americas Health Rankings, a composite index of >20
factors, Texas ranked 34th in overall health in 2015 (10). The
report, put out by United Health Foundation, established by
UnitedHealth Group, parent of insurer UnitedHealth Care,
showed that Texas had one of the largest declines among US
233
states for 2015. The ve healthiest states were Hawaii, Vermont,

Massachusetts, Minnesota, and New Hampshire, and the ve
least healthy states were Alabama, West Virginia, Arkansas, Mississippi, and Louisiana. Texas rank among states in smoking was
5th (14.5%); excessive alcohol drinking, 25th (17.4%); obesity
(body mass index >30 kg/m), 40th (32%); physical inactivity,
43rd (28%); childhood immunizations, 48th (64%); and lack of
health insurance, 50th (21%). Texas had the seventh lowest rate
of drug-related deaths (10 per 100,000 population). Of high
school students graduating within 4 years of starting the ninth
grade, Texas had the third highest percentage (88%), trailing
only Iowa and Nebraska. Consumers with more education are
less likely to smoke, drink alcohol heavily, or be overweight or
obese. They are also likely to have higher earning potential and
better employment opportunities, factors generally associated
with access to healthier food, better health insurance, better
medical care, and safer neighborhoods.
INTERRUPTED LONG SLEEP VERSUS CONTINUOUS SHORTER
SLEEP
In a study published in November 2015 in the journal Sleep,
researchers from The Johns Hopkins University School of Medicine found that people forced to awaken multiple times during
the night showed a greater decline in positive mood than those
forced to go to bed later (11). They also had less slow-wave or
deep sleep, the third stage of non-rapid eye movement sleep. A
2013 study from Israel found that a fragmented night of sleep
for a full 8 hours impacted mood and attention as much as
sleeping continuously 4 hours a night. A study from the University of Pittsburgh showed that the cognitive performance of
elderly people was impaired when their sleep was disrupted but
not when they slept a shorter amount of time straight through.
The recent study from Hopkins included healthy people
without any diagnosed sleep problems. The 62 subjects were
brought into the lab and randomized into three groups: a group
whose sleep was repeatedly disrupted; a group whose bedtime
was delayed; and a control group. The subjects were given 8
hours to sleep in the lab for three consecutive nights. Those in
the disrupted group were awakened each hour. Those in the
forced awakening group showed a decline in mood during the 3
days, while those in the delayed bedtime group saw their moods
stabilized over the 3 days. Thus, a good nights sleep is not just
about how long one sleeps; uninterrupted short sleep time may
be better or at least equivalent to long interrupted sleep time.
DIABETES DECLINING
According to researchers at the CDC, the rst decline in
25 years in the rate of new cases of diabetes mellitus was noted
between 2008 and 2014, a 20% decrease (12). There were 1.4
million new cases of diabetes in 2014, down from 1.7 million
in 2008. There is growing evidence that eating habits, after
decades of deterioration, have nally begun to improve. The
amount of soda Americans drink has declined by about 25%
since the late 1990s, and the average number of daily calories
children and adults consume also has fallen. Physical activity
has started to rise and once-surging rates of obesity have at234
tened. Type I diabetes mellitus, usually diagnosed in childhood

and adolescents and usually not associated with excessive body
weight, was included in the data. The portion of Americans
with diabetes is still more than double what it was in the early
1990s! Educated Americans have seen improvements, while the
rates for the less educated have attened but not declined. The
number of new cases is dropping for whites, but the change
has not been statistically signicant for blacks or Hispanics,
although both show a downward trend. Diabetes still aects 1
in every 10 American adults and is the countrys leading cause
of blindness, limb amputations, and kidney dialysis.
SYNAPTIC PRUNING AND SCHIZOPHRENIA
In the January 2016 issue of Nature was a report indicating that researchers had pieced together the steps by which
genes can increase a persons risk of developing schizophrenia, a
condition aecting >2 million Americans and characterized by
delusional thinking and hallucinations (13). The investigators
found that the risk of schizophrenia is tied to a natural process
called synaptic pruning in which the brain sheds weak or redundant connections between neurons as it matures. Their nding
helps explain why this disorder often begins in adolescence or
young adulthood. During this time, synaptic pruning takes
place primarily in the section of the brain where thinking and
planning skills are centered, known as the prefrontal cortex.
People who carry genes that accelerate or intensify that pruning
are at higher risk of developing schizophrenia than those who do
not. Earlier studies with patients with schizophrenia had shown
that the prefrontal areas tended to have fewer neural connections
compared with those of unaected people. The new study not
only strongly supports this earlier belief but also describes how
pruning probably goes wrong and why and identies the genes
responsible. People with schizophrenia have a gene variant that
apparently facilitates aggressive tagging of connections for
pruning, in eect accelerating the process.
THE END OF THE ONE-CHILD POLICY IN CHINA
The Chinese government announced in December 2015
that it has ended its one-child policy and will replace it with a
universal two-child policy (14). The one-child policy profoundly
aected the lives of 20% of the worlds population for 35 years!
The one-child policy introduced in 1979 by Deng Xiao Ping
(who saw population containment as essential to his ambitious
economic reform program) was designed to improve standards
of living after decades of economic stagnation. The decision to
introduce an unpopular population policy was made despite a
substantial reduction in the total fertility rate (TFR, dened
as the average number of children born per woman) from an
estimated 5.9 to 2.9 in the previous decade. This reduction
had been achieved entirely through voluntary measures, and
the TFR was still declining when the policy was introduced.
Thailands fertility trajectory has been almost identical in the
absence of a government mandate.
From the outset, the one-child policy was strictly enforced
for urban residents but not for rural residents. It soon became
clear that a one-child rule was unenforceable because of the
Volume 29, Number 2
importance of labor capital in the family-based agrarian economy, dependence on children in old age, and the tradition of
son preference. From 1984, most of the rural couples were
allowed two children, although, in some provinces, only when
the rst child was a girl. The policy was enforced through a
system of rewards and penalties, such as substantial nes and
loss of employment, especially for public-sector workers, but
with wide variations across the country.
On the positive side, during the one-child policy time period, the TFR fell from 2.9 to around 1.6. The government claims
that this policy prevented 400 million births while helping to lift
300 million people out of poverty. Women have beneted from
fewer pregnancies and births, with consequent lower lifetime
morbidity and mortality risk. The policy accelerated the move
toward gender equality. Under the traditional Chinese system
of patrilineal kinship, parents invested relatively little in their
daughters, but in the absence of brothers, girls no longer competed for household resources. Recent studies have found no
signicant dierences between single girl and single boy families
in education, in terms of access, aspiration, or achievement.
Women now account for 52% of undergraduates and 48%
of postgraduates, as well as 25% of chief executive ocers of
medium and large Chinese companies.
From the negative standpoint, the one-child policy may
be viewed as a violation of the right to reproductive choice. Its
implementation has resulted in well-documented atrocities,
such as forced abortions and sterilizations. The policy has contributed to the highest sex ratio at birth in the world, peaking
in 2005 at 121 male to 100 female births. The sex ratio at birth
started to increase after the onset of the policy, but this trend accelerated after sex-selective technology (ultrasound followed by
abortion of the female fetus) became available, even in the rural
areas, from the late 1980s. The latest estimates show a decline
to 116 male births to 100 female births, still the highest in the
world, and with ratios up to 140 in parts in rural China. The
number of excess men in the reproductive age group is estimated
at around 30 million, with large numbers of unmarriageable
men in high sex-ratio areas. Evidence indicates that these men
have higher levels of depression, are more prone to aggression
than married men, and may be more easily drawn into crime.
The policy has also created the so-called 4:2:1 phenomenon,
with many couples solely responsible for the care of one child
and four grandparents. One-quarter of the worlds population
65 years, or 140 million people, live in China, and the number
is estimated to increase to >200 million by 2030. The pressure
on the health system resulting from the increasing burden of
noncommunicable diseases and degenerative disorders is one of
Chinas most serious challenges. Because out-of-pocket health
costs are high in China and approximately 70% of this age
group lacks adequate pension coverage, they are highly nancially dependent on ospring. This is further compounded by
the fact that approximately 40% of the elderly now live away
from their children and 10% live alone. This is a particular
problem in rural areas because of mass migration of the young
to cities. This occurs in a setting where Confucian tradition still
dictates that care of the elderly is a lial duty. China is probably
April 2016
unique in having laws that make care of the elderly a family

responsibility, and adult children may be compelled to provide
nancial support.
It is ironic that after decades of draconian restrictions on
fertility, the government is now concerned about the economic
consequences of future labor shortages, concomitant with a
high age-dependency ratio, and will now encourage couples to
have two children.
NATURAL FOOD
What is it? About 60% of the US population regularly buys
food labeled natural, yet there is confusion as to what that
word means. The word has never been legally dened. At least
60% of people believe a natural label means packaged and processed foods that have no genetically modied organisms, no
articial ingredients or colors, no chemicals, and no pesticides.
About 45% think that natural is a veried claim. It is not! In
fact, according to a piece in USA Today by Hadley Malcolm
(15), none of these attributes is necessarily true because the use
of the word is not regulated. The FDA apparently is going to
take a closer look sometime this year at how the word is used and
whether it should be dened and how. According to the FDA
website, a long-standing policy interprets natural to mean
nothing articial or synthetic has been added to a food that
would not normally be expected in that food. The FDA does
not intend to address food production, processing, or manufacturing methods. Shoppers unfortunately appear to be on
the lookout for certain words and use them as purchase signals
regardless of whether the claims are regulated or not. If there
is a health claim on the front of the package, that is what we
zero in on apparently. Consumer Reports identied seven products with natural claims that also contain articial ingredients
or chemicals: Del Monte Fruit Naturals, All-Natural Alexia
Sweet Potato Fries, Krakus Polish Sliced Ham, Natural Brew
Draft Root Beer, Tyson Grilled & Ready Frozen Southwestern Chicken Breast Strips, Kraft Natural Cheese, and Wesson
Vegetable Oil. Denitions are wonderful things. Thats why the
dictionary has been around so long.
LIMITED CALORIC DIVERSITY
Simran Sethi discussed our dwindling food variety (16). In
1903, US commercial seed houses oered hundreds of varieties.
The following numbers were oered in 1903, followed by the
numbers (in parentheses) oered in 1983: muskmelon, 338
(227); lettuce, 497 (236); sweet corn, 307 (12); cabbage, 544
(28); beets, 288 (217); peas, 408 (25); radish, 463 (27); squash,
341 (40); tomato, 408 (279); cucumber, 285 (16). There are
now 7500 varieties of apples grown all over the world, <100 of
which are grown commercially in the USA. Bananas, Americas
most popular fruit, have 1000 varieties grown in the world. The
only one on grocery store shelves in the USA is not the one that
has the best texture or taste but the one that transports easily
and is immune to certain diseases. There are 30,000 edible plant
species, and we cultivate about 150. Of the 30 domesticated
mammalian and bird species, 14 provide 90% of the human
food supply. Of the worlds food, 75% comes from 12 plants
235
and 5 animal species. Plants account for over 80% of the human
diet: 30,000 terrestrial plants are known to be edible, but only
7000 are cultivated or collected by humans for food. Thirty
crops feed the world.
DAILY WRITING
Charlie Kempthorne, now 78 years old, began writing in
his My Journal at age 26 in 1964 and has logged about 1000
to 3000 words daily on his computer during each of these past
52 years (17). By his rough calculations, his journal is about
10 million words long. Every month, he prints the last 30 days
of entries (single-spaced, two-sided) and puts it in a three-ring
binder. His collective writings occupy about 15 feet of shelf
space in a storage unit in Manhattan, Kansas, where he lived
before moving last year. No one, including his wife of 41 years,
has read it. Mr. Kempthorne, who quit a university teaching
job in his 30s to run a farm and small housecleaning business,
says his writing helps him understand his life better. It makes
him simply feel better and gets him started on the day in a
better mood.
Psychology professor James Pennebaker at the University of
Texas and author of several books, including Writing to Heal,
says, Taking 15 or 20 minutes to write freely about emotions,
secrets or upheaval can be a powerful tonic. Writing privately
about traumatic experiences, even for as few as 4 consecutive
days, can reduce stress, help people sleep, and improve their
immune system, says Dr. Pennebaker. When you translate an
emotional experience into words, it organizes them in ways not
organized before. It makes them simpler and easier to get past.
When Charlie Kempthorne sits down to write every morning, he often has no idea what he will write until he opens the
folder labeled My Journal on his computer. One day he might
write about going to the Goodwill Store in Olympia, where
he now lives. The next day he might recall ghting with a boy
named Jimmy over whose dad was best and telling Jimmy his
father didnt get anything to eat but vegetables. He will sometimes consult a list of phrases kept in another computer le or
on paper that refers to events in his past that he might want
to write about. Once he starts writing he begins to remember
things, people, and conversations. It reminds him of his farm in
Kansas, which was covered with rocks that needed to be cleared
before he could plow.
He prefers the computer to longhand because typing is
faster. The faster I write the better I write. If I dont write each
day I feel something is missing. His wife, June, says he is out
of sorts if he skips a session.
Charlie Kempthorne has some advice on how to build a
daily writing habit: Write 500 words every day for 28 consecutive days, preferably at the same time and same place to create a
routine. Dont worry about grammar or punctuation. Be willing
to write badly. Authenticity is more important than excellence.
Use prompts to get you going. Make a list of six stories you commonly
tell. Get a photo and tell the story of that picture. Keep it private.
If you show it to others you might worry about what they will
say and never start. If you cant think of what to write, describe
the room you are in, what you are wearing or a room from your
236
childhood home, or what it felt like to brush your teeth. Carry a

notebook to jot down ideas or a recollection, conversation, or image.
KONDOING
Marie Kondo is the author of The Life-Changing Magic of
Tidying Up (2014) and Spark Joy: An Illustrated Master Class on
the Art of Organizing and Tidying Up (2016) (18). Marie Kondo,
who refers to herself as KonMari, is a phenomenon in Japan
and becoming one in the USA. Her view in essence is that a
neat home is a happy home. Kondo oers her tips with a side of
existential advice. She counsels that the best way to choose what
to keep and what to throw away is to take each item in ones
hand and ask: Does this spark joy? If it does, keep it. If not,
dispose of it. Kondo instructs her readers to ask themselves of
each item in their home, Am I having trouble getting rid of this
because of an attachment to the past or because of a fear for the
future? Tidying is the act of conrming yourself. Kondo writes
in her new book, Cleaning is the act of confronting nature.
In the US, women take on more domestic responsibilities
than their male partners. Women in the USA spend an average
of 2 hours more on chores a week than men. In one British
survey, men acknowledged deliberately doing a poor job of
cleaning the toilet, loading the dishwasher, and vacuuming so
that their female partners would be more inclined to tackle those
chores themselves. Even the most equally minded heterosexual
couples can nd themselves defaulting to familiar roles when
it comes to the mundane tasks of homemaking.
GLOBAL WARMING
US agencies released gures in January 2016 showing that
2015 was the warmest year since 1880, when the global record
began (19, 20). The previous record was in 2014. December
2015 was especially remarkable in the US, with virtually every
state east of the Mississippi River having a record warm month
often accompanied by heavy rains. A warmer atmosphere can
hold more water vapor, and intensication of rain storms was
one of the fundamental predictions made by climate scientists
decades ago as a consequence of human-produced emissions.
That prediction has come true with the rains growing more intense in every region of the US, especially in the East. The term
global warming is generally taken to refer to the temperature
trend at the surface of the planet. Some additional measurements of shorter duration are available for the ocean depths
and the atmosphere above the surface, both generally showing
an inexorable long-term warming trend.
The intense warmth of 2015 produced a heat wave in India
that turned out to have been the second worst in that countrys
history, killing an estimated 2500 people. Of the 10 deadliest
heatwaves, eight have occurred since 1997. Although only rough
estimates of heat deaths are available, according to gures from
the Center for Research on the Epidemiology of Disasters in
Brussels, the toll over the last 2 decades is approaching 140,000
people, with most of those deaths occurring during a European
heat wave in 2003 and a Russian heat wave in 2010.
The strong El Nio has continued into 2016, raising the
possibility that this year will yet again set a global temperature
Volume 29, Number 2
record. The El Nio pattern also is disturbing the circulation of

the atmosphere, contributing to worldwide weather extremes
that include a drought in Southern Africa threatening the food
supply of millions. The National Oceanic and Atmospheric Administration calculated the 2015 global temperature at 58.62,
or 1.62 above the 20th century average.
5.
6.
7.
8.
ROGER STAUBACH AND HAIL MARY

It was on December 28, 1975, with only 32 seconds remaining in a National Football Conference playo game (Dallas
Cowboys vs. Minnesota Vikings) when Roger Staubach completed a winning 50-yard touchdown pass to wide receiver Drew
Pearson (21). After the game, Staubach, a lifelong Catholic, said,
I closed my eyes and said a Hail Mary. And now, nearly half
a century later, the phrase is often used. We owe it to Roger
Staubach.
9.
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12.
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14.
15.
16.
William Clifford Roberts, MD

February 9, 2016
1.
2.
3.
4.
Whalen J. US drug prices dwarf other nations. Wall Street Journal,

December 1, 2015.
Greene MT, Saint S. Flu shots for hospital workers save lives. Wall Street
Journal, December 14, 2015.
Szabo L. Zika virus threatens to hit USA. USA Today, January 28, 2016.
AP. NFL briefs: Concussions increase. Dallas Morning News, January 30,
2016.
April 2016
17.
18.
19.
20.
21.
Weaver C, Wilde Mathews C, McGinty T. New risks at rural hospitals.

Wall Street Journal, December 2627, 2015.
Burns S. For a longer life, try being a nerd. Dallas Morning News, January
24, 2016.
Berra K, Rippe J, Manson JE. Making physical activity counseling a priority
in clinical practice: the time for action is now. JAMA 2015;314(24):2617
2618.
Kendall J. The Man Who Made Lists: Love, Death, Madness, and the Creation
of Rogets Thesaurus. New York: Penguin Group, 2008 (297 pp.).
Eknoyan G. Adolphe Quetelet (17961874)the average man and
indices of obesity. Nephrol Dial Transplant 2008;23(1):4751.
Robinson-Jacobs K. Texans bigger but not better in health rankings. Dallas
Morning News, December 10, 2015.
Reddy S. Less sleep can feel better than interruptions. Wall Street Journal,
December 1, 2015.
Tavernise S. New cases of diabetes in US decline. New York Times,
December 1, 2015.
Carey B. Schizophrenias cause explored. New York Times, January 29,
2016.
Hesketh T, Zhou X, Wang Y. The end of the one-child policy: lasting
implications for China. JAMA 2015;314(24):26192620.
Malcolm H. More buying natural food, but its unclear what that is. USA
Today, January 29, 2016.
Sethi S. Your varied diet isnt really so varied. Dallas Morning News, January
24, 2016.
Ansberry C. 52 years and counting: the power of daily writing. Wall Street
Journal, January 27, 2016.
Friedman A. Men miss Magic of Tidying Up. Dallas Morning News,
January 31, 2016.
Wire reports. 2015: hottest year on record. Dallas Morning News, January
21, 2016.
Englis B. Conservatives need to thaw on warming. USA Today, January
22, 2016.
Granberry M. All hail the Hail Mary at 40. Dallas Morning News,
December 29, 2015.
237
2015
publications of the Baylor Scott

& White Health North Division
medical and scientific staff
ANESTHESIOLOGY AND PAIN MANAGEMENT

1. Barker SJ, Shander A, Ramsay MA. Continuous noninvasive hemoglobin
monitoring: a measured response to a critical review. Anesth Analg 2015
Mar 5 [Epub ahead of print].
2. Idris AH, Guey D, Pepe PE, Brown SP, Brooks SC, Callaway CW,
Christenson J, Davis DP, Daya MR, Gray R, Kudenchuk PJ, Larsen J, Lin
S, Menegazzi JJ, Sheehan K, Spoko G, Stiell I, Nichol G, Aufderheide TP;
Resuscitation Outcomes Consortium Investigators [Ramsay M]. Chest
compression rates and survival following out-of-hospital cardiac arrest.
Crit Care Med 2015;43(4):840848.
3. Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfelt M, Stiell
I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk
P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R,
Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S,
Ornato JP; Resuscitation Outcomes Consortium Investigators [Ramsay
M]. Trial of continuous or interrupted chest compressions during CPR.
N Engl J Med 2015 Nov 9 [Epub ahead of print].
4. Ramsay M. Breathing is good. J Clin Monit Comput 2015;29(2):221222.
5. Rauck R, Parikh N, Dillaha L, Barker J, Stearns L. Patient satisfaction with
fentanyl sublingual spray in opioid-tolerant patients with breakthrough
cancer pain. Pain Pract 2015;15(6):554563.
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CARDIOLOGY/CARDIAC, VASCULAR, AND THORACIC SURGERY

6. Abramowitz Y, Jilaihawi H, Chakravarty T, Mack MJ, Makkar RR. Mitral
annulus calcication. J Am Coll Cardiol 2015;66(17):19341941.
7. Abramowitz Y, Jilaihawi H, Chakravarty T, Mack MJ, Makkar RR. Porcelain
aorta: a comprehensive review. Circulation 2015;131(9):827836.
8. Adams R, Adams J, Qin H, Bilbrey T, Schussler JM. Virtual coaching
for the high-intensity training of a powerlifter following coronary artery
bypass grafting. Proc (Bayl Univ Med Cent) 2015;28(1):7577.
9. Afzal AM, Alsahhar J, Podduturi V, Schussler JM. Undierentiated intimal
sarcoma of the inferior vena cava with extension to the right atrium and
renal vasculature. Case Rep Cardiol 2015;2015:812374.
10. Afzal AM, Sarmast SA, Weber NA, Schussler JM. Spontaneous coronary
artery dissection in a 22-year-old man on lisdexamfetamine. Proc (Bayl
Univ Med Cent) 2015;28(3):367368.
11. Alli O, Rihal CS, Suri RM, Greason KL, Waksman R, Minha S, Torguson
R, Pichard AD, Mack M, Svensson LG, Rajeswaran J, Lowry AM,
Ehrlinger J, Tuzcu EM, Thourani VH, Makkar R, Blackstone EH, Leon
MB, Holmes D. Learning curves for transfemoral transcatheter aortic valve
replacement in the PARTNER-I trial: technical performance. Catheter
Cardiovasc Interv 2015 Aug 10 [Epub ahead of print].
12. Anker SD, Kosiborod M, Zannad F, Pia IL, McCullough PA, Filippatos G,
van der Meer P, Ponikowski P, Rasmussen HS, Lavin PT, Singh B, Yang A,
Deedwania P. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail 2015;17(10):10501056.
13. Arko FR, Gable DR. Why build an aortic center? EndoVasc Today
2015;8(S2):510.
14. Armstrong D, Gonzalez-Stawinski GV, Ko JM, Hall SA, Roberts WC. The
two extremes of cardiac sarcoidosis and the eect of prednisone therapy.
Am J Cardiol 2015;115(1):150153.
15. Arnold SV, Spertus JA, Vemulapalli S, Dai D, OBrien SM, Baron SJ,
Kirtane AJ, Mack MJ, Green P, Reynolds MR, Rumsfeld JS, Cohen DJ.
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Association of patient-reported health status with long-term mortality

after transcatheter aortic valve replacement: report from the STS/ACC
TVT registry. Circ Cardiovasc Interv 2015;8(12).
Arsalan M, Mack M. Coronary artery bypass grafting in patients with
diabetes: the weight is on us. J Thorac Cardiovasc Surg 2015;150(2):284285.
Arsalan M, Mack MJ. Durability of devices: long-term results and clinical
outcomes. EuroIntervention 2015;11(Suppl W):W119W122.
Arsalan M, Squiers JJ, DiMaio JM, Mack MJ. Catheter-based or surgical
repair of the highest risk secondary mitral regurgitation patients. Ann
Cardiothorac Surg 2015;4(3):278283.
Arsalan M, Squiers JJ, Walther T. Preimplantation valvuloplasty in
transcatheter aortic valve replacement: to BAV or not to BAV? J Thorac
Cardiovasc Surg 2015;150(5):11181119.
Arsalan M, Walther T, Smith RL 2nd, Grayburn PA. Tricuspid regurgitation diagnosis and treatment. Eur Heart J 2015 Sep 10 [Epub ahead
of print].
Asgar AW, Mack MJ, Stone GW. Secondary mitral regurgitation in heart
failure: pathophysiology, prognosis, and therapeutic considerations. J Am
Coll Cardiol 2015;65(12):12311248.
Asgar AW, Mack MJ, Stone GW. Reply: Secondary mitral regurgitation.
J Am Coll Cardiol 2015;66(17):1947.
Barbin CM, Grayburn PA, Choi JW. Successful MitraClip implantation
after angioplasty of a chronic inferior vena cava lter thrombosis. Catheter
Cardiovasc Interv 2015 Jun 23 [Epub ahead of print].
Barbin CM, Weissenborn MR, Ko JM, Guileyardo JE, Roberts WC.
Computed tomographic and morphologic features of syphilis of the aorta.
Am J Cardiol 2015;116(8):13111314.
Bavaria JE, Brinkman WT, Hughes GC, Khoynezhad A, Szeto WY,
Azizzadeh A, Lee WA, White RA. Outcomes of thoracic endovascular
aortic repair in acute type B aortic dissection: results from the Valiant
United States investigational device exemption study. Ann Thorac Surg
2015;100(3):802808.
Bhak RH, Wininger M, Johnson GR, Lederle FA, Messina LM, Ballard
DJ, Wilson SE; Aneurysm Detection and Management (ADAM)
Study Group. Factors associated with small abdominal aortic aneurysm
expansion rate. JAMA Surg 2015;150(1):4450.
Blackstone EH, Suri RM, Rajeswaran J, Babaliaros V, Douglas PS, Fearon
WF, Miller DC, Hahn RT, Kapadia S, Kirtane AJ, Kodali SK, Mack
M, Szeto WY, Thourani VH, Tuzcu EM, Williams MR, Akin JJ, Leon
MB, Svensson LG. Propensity-matched comparisons of clinical outcomes
after transapical or transfemoral transcatheter aortic valve replacement:
a placement of aortic transcatheter valves (PARTNER)-I trial substudy.
Circulation 2015;131(22):19892000.
Blanke P, Naoum C, Webb J, Dvir D, Hahn RT, Grayburn P, Moss RR,
Reisman M, Piazza N, Leipsic J. Multimodality imaging in the context of
transcatheter mitral valve replacement: establishing consensus among modalities and disciplines. JACC Cardiovasc Imaging 2015;8(10):11911208.
Bourantas CV, Zhang YJ, Garg S, Mack M, Dawkins KD, Kappetein AP,
Mohr FW, Colombo A, Holmes DR, Sthle E, Feldman T, Morice MC, de
Vries T, Morel MA, Serruys PW. Prognostic implications of severe coronary
calcication in patients undergoing coronary artery bypass surgery: an analysis of the SYNTAX study. Catheter Cardiovasc Interv 2015;85(2):199206.
Brinkman WT, Squiers JJ, Covington KR, Wheeler DA, Arsalan M, Smith
RL, Mack MJ, DiMaio J. Mini-extracorporeal circulation and o-pump
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techniques associated with less inammatory gene expression as compared

to on-pump in the 24-hour postoperative window following coronary
artery bypass grafting. J Cardiothorac Surg 2015;10(Suppl 1):A101.
Brinkman WT, Squiers JJ, Filardo G, Arsalan M, Smith RL, Moore D,
Mack MJ, DiMaio JM. Perioperative outcomes, transfusion requirements,
and inammatory response after coronary artery bypass grafting with
o-pump, mini-extracorporeal, and on-pump circulation techniques.
J Investig Med 2015;63(8):916920.
Busken CJ, Grimsley BR, Shutze WP. Iliac artery stenosis complicating
iliac vein stenting in a patient with a history of radiation and cancer:
case report and literature review. Ann Vasc Surg 2015;29(4):843.e715.
Carroll JD, Shuren J, Jensen TS, Hernandez J, Holmes D, Marinac-Dabic
D, Edwards FH, Zuckerman BD, Wood LL, Kuntz RE, Mack MJ. Transcatheter valve therapy registry is a model for medical device innovation
and surveillance. Health A (Millwood) 2015;34(2):328334.
Chan RH, Maron BJ, Olivotto I, Assenza GE, Haas TS, Lesser JR, Gruner
C, Crean AM, Rakowski H, Rowin E, Udelson J, Lombardi M, Tomberli
B, Spirito P, Formisano F, Marra MP, Biagini E, Autore C, Manning WJ,
Appelbaum E, Roberts WC, Basso C, Maron MS. Signicance of late gadolinium enhancement at right ventricular attachment to ventricular septum in patients with hypertrophic cardiomyopathy. Am J Cardiol 2015;116(3):436441.
Charytan DM, Fishbane S, Malyszko J, McCullough PA, Goldsmith D.
Cardiorenal syndrome and the role of the bone-mineral axis and anemia.
Am J Kidney Dis 2015;66(2):196205.
Chen S, Chen J, Huang P, Meng XL, Clayton S, Shen JS, Grayburn
PA. Myocardial regeneration in adriamycin cardiomyopathy by nuclear
expression of GLP1 using ultrasound targeted microbubble destruction.
Biochem Biophys Res Commun 2015;458(4):823829.
Chen J, Chen S, Huang P, Meng XL, Clayton S, Shen JS, Grayburn PA.
In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in
rats. Diabetologia 2015;58(5):10361044.
Coylewright M, Mack MJ, Holmes DR Jr, OGara PT. A call for an
evidence-based approach to the heart team for patients with severe aortic
stenosis. J Am Coll Cardiol 2015;65(14):14721480.
Cumbie TA, Kedora JC, Pearl GJ, Shutze WP. A hybrid repair of a superior
mesenteric artery pseudoaneurysm using open mesenteric bypass and
endovascular exclusion. Proc (Bayl Univ Med Cent) 2015;28(3):355357.
Cutlip DE, Kereiakes DJ, Mauri L, Stoler R, Dauerman HL; EDUCATE Investigators. Thrombotic complications associated with early and
late nonadherence to dual antiplatelet therapy. JACC Cardiovasc Interv
2015;8(3):404410.
Douglas PS, Hahn RT, Pibarot P, Weissman NJ, Stewart WJ, Xu K, Wang
Z, Lerakis S, Siegel R, Thompson C, Gopal D, Keane MG, Svensson LG,
Tuzcu EM, Smith CR, Leon MB. Hemodynamic outcomes of transcatheter aortic valve replacement and medical management in severe, inoperable aortic stenosis: a longitudinal echocardiographic study of cohort B of
the PARTNER trial. J Am Soc Echocardiogr 2015;28(2):210217.e19.
Falcone AM, Varghese JJ, Stoler RC, Choi JW. Eectiveness of balloon
valvuloplasty for stenosis of a bioprosthesis in the tricuspid valve position.
Proc (Bayl Univ Med Cent) 2015;28(4):502503.
Fallahzadeh MK, McCullough PA. Cardiac electromechanical abnormalities in hemodialysis patients: indicators of cardiomyopathy and future
risk. Am J Nephrol 2015;42(3):237238.
Farber A, Tan TW, Hu B, Dember LM, Beck GJ, Dixon BS, Kusek JW,
Feldman HI; Dialysis Access Consortium (DAC) Study Group. The eect
of location and conguration on forearm and upper arm hemodialysis
arteriovenous grafts. J Vasc Surg 2015;62(5):12581264.
Feldman T, Kar S, Elmariah S, Smart SC, Trento A, Siegel RJ, Apruzzese
P, Fail P, Rinaldi MJ, Smalling RW, Hermiller JB, Heimansohn D, Gray
WA, Grayburn PA, Mack MJ, Lim DS, Ailawadi G, Herrmann HC, Acker
MA, Silvestry FE, Foster E, Wang A, Glower DD, Mauri L; EVEREST II
Investigators. Randomized comparison of percutaneous repair and surgery
for mitral regurgitation: 5-year results of EVEREST II. J Am Coll Cardiol
2015;66(25):28442854.
Filardo G, Powell JT, Martinez MA, Ballard DJ. Surgery for small
asymptomatic abdominal aortic aneurysms. Cochrane Database Syst Rev
2015;2:CD001835.
April 2016
47. Flack JM, Bhatt DL, Kandzari DE, Brown D, Brar S, Choi JW, DAgostino
R, East C, Katzen BT, Lee L, Leon MB, Mauri L, ONeill WW, Oparil S,
Rocha-Singh K, Townsend RR, Bakris G; SYMPLICITY HTN-3 Investigators. An analysis of the blood pressure and safety outcomes to renal
denervation in African Americans and non-African Americans in the
SYMPLICITY HTN-3 trial. J Am Soc Hypertens 2015;9(10):769779.
48. Frost PA, Chen S, Mezzles MJ, Voruganti VS, Nava-Gonzalez EJ, ArriagaCazares HE, Freed KA, Comuzzie AG, DeFronzo RA, Kent JW Jr, Grayburn
PA, Bastarrachea RA. Successful pharmaceutical-grade streptozotocin (STZ)induced hyperglycemia in a conscious tethered baboon (Papio hamadryas)
model. J Med Primatol 2015;44(4):202217.
49. Gable DR. Covered stent grafts in the SFA are still the endovascular
champion in long lesions. Vasc Spec 2015;11(4):8.
50. Garcia MJ, Blankstein R, Budo MJ, Dent JM, Drachman DE, Lesser
JR, Grover-McKay M, Schussler JM, Voros S, Wann LS. COCATS 4 Task
Force 7: training in cardiovascular computed tomographic imaging. J Am
Coll Cardiol 2015;65(17):18101812; J Nucl Cardiol 2015;22(4):826839.
51. Gnreux P, Campos CM, Farooq V, Bourantas CV, Mohr FW, Colombo
A, Morel MA, Feldman TE, Holmes DR Jr, Mack MJ, Morice MC, Kappetein AP, Palmerini T, Stone GW, Serruys PW. Validation of the SYNTAX revascularization index to quantify reasonable level of incomplete
revascularization after percutaneous coronary intervention. Am J Cardiol
2015;116(2):174186.
52. Gillinov AM, Gelijns AC, Parides MK, DeRose JJ Jr, Moskowitz AJ,
Voisine P, Ailawadi G, Bouchard D, Smith PK, Mack MJ, Acker MA,
Mullen JC, Rose EA, Chang HL, Puskas JD, Couderc JP, Gardner TJ,
Varghese R, Horvath KA, Bolling SF, Michler RE, Geller NL, Ascheim
DD, Miller MA, Bagiella E, Moquete EG, Williams P, Taddei-Peters WC,
OGara PT, Blackstone EH, Argenziano M; CTSN Investigators. Surgical
ablation of atrial brillation during mitral-valve surgery. N Engl J Med
2015;372(15):13991409.
53. Gopal A, Grayburn PA, Mack M, Chacon I, Kim R, Montenegro D, Phan
T, Rudolph J, Filardo G, Mack MJ, Gopalakrishnan D. Noncontrast 3D
CMR imaging for aortic valve annulus sizing in TAVR. JACC Cardiovasc
Imaging 2015;8(3):375378.
54. Grayburn PA, Carabello B, Hung JW, Gillam LD, Liang D, Mack MJ,
McCarthy PM, Miller DC, Trento A, Siegel RJ. Reply: When to call it
severe mitral regurgitation? J Am Coll Cardiol 2015;65(25):27672768.
55. Grayburn PA, She L, Roberts BJ, Golba KS, Mokrzycki K, Drozdz J,
Cherniavsky A, Przybylski R, Wrobel K, Asch FM, Holly TA, Haddad H,
Yii M, Maurer G, Kron I, Scha H, Velazquez EJ, Oh JK. Comparison
of transesophageal and transthoracic echocardiographic measurements of
mechanism and severity of mitral regurgitation in ischemic cardiomyopathy (from the Surgical Treatment of Ischemic Heart Failure Trial). Am J
Cardiol 2015;116(6):913918.
56. Green P, Arnold SV, Cohen DJ, Kirtane AJ, Kodali SK, Brown DL, Rihal
CS, Xu K, Lei Y, Hawkey MC, Kim RJ, Alu MC, Leon MB, Mack MJ.
Relation of frailty to outcomes after transcatheter aortic valve replacement
(from the PARTNER trial). Am J Cardiol 2015;116(2):264269.
57. Hahn RT, Kodali S, Tuzcu EM, Leon MB, Kapadia S, Gopal D, Lerakis
S, Lindman BR, Wang Z, Webb J, Thourani VH, Douglas PS. Echocardiographic imaging of procedural complications during balloonexpandable transcatheter aortic valve replacement. JACC Cardiovasc
Imaging 2015;8(3):288318.
58. Hamm CW, Arsalan M, Mack MJ. The future of transcatheter aortic valve
implantation. Eur Heart J 2015 Nov 17 [Epub ahead of print].
59. Harrison JK, Hughes GC, Reardon MJ, Stoler RC, Grayburn PA, Hebeler
RF, Popma JJ. Balloon post-dilation of the self-expanding CoreValve transcatheter aortic valve bioprosthesis: procedural results and in hospital outcomes from 3532 patients in the CoreValve US pivotal and continued
access trials. J Am Coll Cardiol 2015;66(15S).
60. Harskamp RE, Alexander JH, Ferguson TB Jr, Hager R, Mack MJ, Englum
B, Wojdyla D, Schulte PJ, Kouchoukos NT, de Winter RJ, Gibson CM,
Peterson ED, Harrington RA, Smith PK, Lopes RD. Frequency and predictors of internal mammary artery graft failure and subsequent clinical
outcomes: insights from the PREVENT IV Trial. Circulation 2015 Dec
8 [Epub ahead of print].
2015 publications of the Baylor Scott & White Health North Division medical and scientic staff
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61. Harskamp RE, Halkos ME, Xian Y, Szerlip MA, Poston RS, Mick SL,
Lopes RD, Tijssen JG, de Winter RJ, Peterson ED. A nationwide survey on
perception, experience, and expectations of hybrid coronary revascularization among top-ranked US hospitals. Am Heart J 2015;169(4):557563.e6.
62. Head SJ, Parasca CA, Mack MJ, Mohr FW, Morice MC, Holmes DR
Jr, Feldman TE, Dawkins KD, Colombo A, Serruys PW, Kappetein AP;
SYNTAX Investigators. Dierences in baseline characteristics, practice
patterns and clinical outcomes in contemporary coronary artery bypass
grafting in the United States and Europe: insights from the SYNTAX randomized trial and registry. Eur J Cardiothorac Surg 2015;47(4):685695.
63. Hess CN, Lopes RD, Gibson CM, Hager R, Wojdyla DM, Englum
BR, Mack MJ, Kouchoukos NT, Peterson ED, Alexander JH. Response
to letters regarding article, Saphenous vein graft failure after coronary artery bypass surgery: insights from PREVENT IV. Circulation
2015;132(4):e29.
64. Hijazi ZM, Ruiz CE, Zahn E, Ringel R, Aldea GS, Bacha EA, Bavaria
J, Bolman RM 3rd, Cameron DE, Dean LS, Feldman T, Fullerton D,
Horlick E, Mack MJ, Miller DC, Moon MR, Mukherjee D, Trento A,
Tommaso CL. SCAI/AATS/ACC/STS operator and institutional requirements for transcatheter valve repair and replacement, part III: pulmonic
valve. J Am Coll Cardiol 2015;65(23):25562563; Ann Thorac Surg
2015;99(5):18571864; J Thorac Cardiovasc Surg 2015;149(5):e71e78;
Catheter Cardiovasc Interv 2015;86(1):8593.
65. Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, OBrien SM, Vemulapalli S, Edwards FH, Carroll J, Shahian D, Grover F, Tuzcu EM,
Peterson ED, Brindis RG, Mack MJ; STS/ACC TVT registry. Clinical
outcomes at 1 year following transcatheter aortic valve replacement. JAMA
2015;313(10):10191028.
66. Holmes DR Jr, Mack MJ. Moores law: apples and oranges. JACC Cardiovasc Interv 2015;8(13):16671669.
67. Holmes DR Jr, Nishimura RA, Grover FL, Brindis RG, Carroll JD,
Edwards FH, Peterson ED, Rumsfeld JS, Shahian DM, Thourani
VH, Tuzcu EM, Vemulapalli S, Hewitt K, Michaels J, Fitzgerald S,
Mack MJ; STS/ACC TVT Registry. Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT registry. J Am Coll Cardiol
2015;66(25):28132823.
68. Husain-Syed F, McCullough PA, Birk HW, Renker M, Brocca A, Seeger
W, Ronco C. Cardio-pulmonary-renal interactions: a multidisciplinary
approach. J Am Coll Cardiol 2015;65(22):24332448.
69. Iqbal J, Zhang YJ, Holmes DR, Morice MC, Mack MJ, Kappetein AP,
Feldman T, Stahle E, Escaned J, Banning AP, Gunn JP, Colombo A,
Steyerberg EW, Mohr FW, Serruys PW. Optimal medical therapy improves clinical outcomes in patients undergoing revascularization with
percutaneous coronary intervention or coronary artery bypass grafting:
insights from the Synergy Between Percutaneous Coronary Intervention
with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year followup. Circulation 2015;131(14):12691277.
70. Jacobs JP, OBrien SM, Pasquali SK, Gaynor JW, Mayer JE Jr, Karamlou
T, Welke KF, Filardo G, Han JM, Kim S, Quintessenza JA, Pizarro C,
Tchervenkov CI, Lacour-Gayet F, Mavroudis C, Backer CL, Austin EH
3rd, Fraser CD, Tweddell JS, Jonas RA, Edwards FH, Grover FL, Prager
RL, Shahian DM, Jacobs ML. The Society of Thoracic Surgeons congenital
heart surgery database mortality risk model: part 2clinical application.
Ann Thorac Surg 2015;100(3):10631068.
71. Kapadia S, Stewart WJ, Anderson WN, Babaliaros V, Feldman T, Cohen
DJ, Douglas PS, Makkar RR, Svensson LG, Webb JG, Wong SC, Brown
DL, Miller DC, Moses JW, Smith CR, Leon MB, Tuzcu EM. Outcomes
of inoperable symptomatic aortic stenosis patients not undergoing aortic
valve replacement: insight into the impact of balloon aortic valvuloplasty
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72. Kapadia SR, Leon MB, Makkar RR, Tuzcu EM, Svensson LG, Kodali S,
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JJ, Miller DC, Smith CR, Leon MB. Response to letter regarding article,
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Mack M. Balancing optimal outcomes with access to care: it can be done!
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Mack M. Can we make stroke during cardiac surgery a never event?
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98. McCullough PA, Jeeries JL. Novel markers and therapies for patients with acute heart failure and renal dysfunction. Am J Med
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101. McCullough PA, Young A, Shutze WP. Acute kidney injury after carotid
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102. Minha S, Waksman R, Satler LP, Torguson R, Alli O, Rihal CS, Mack M,
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106. ONeill BP, Guerrero M, Thourani VH, Kodali S, Heldman A, Williams
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134. Stone GW, Vahanian AS, Adams DH, Abraham WT, Borer JS, Bax JJ,
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137. Suri RM, Gulack BC, Brennan JM, Thourani VH, Dai D, Zajarias A,
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J Thorac Cardiovasc Surg 2015;150(3):557568.e11.
139. Tger T, Schell M, Cebola R, Frhlich H, Dsch A, Franke J, Katus HA,
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152.
(RCV) and minimal important dierence (MID) of inspiratory muscle

strength (PImax) in patients with stable chronic heart failure. Clin Res
Cardiol 2015;104(10):822830.
Tecson KM, Silver MA, Brune SD, Cauthen C, Kwan MD, Schussler
JM, Vasudevan A, Watts JA, McCullough PA. Impact of enhanced external counterpulsation on heart failure rehospitalization in patients
with ischemic cardiomyopathy. Am J Cardiol 2015 Dec 31 [Epub ahead
of print].
Thijs VN, Brachmann J, Morillo CA, Passman RS, Sanna T, Bernstein
RA, Diener HC, Di Lazzaro V, Rymer MM, Hogge L, Rogers TB, Ziegler
PD, Assar MD. Predictors for atrial brillation detection after cryptogenic stroke: Results from CRYSTAL AF. Neurology 2015 Dec 18 [Epub
ahead of print].
Thourani VH, Jensen HA, Babaliaros V, Kodali SK, Rajeswaran J, Ehrlinger J, Blackstone EH, Suri RM, Don CW, Aldea G, Williams MR,
Makkar R, Svensson LG, McCabe JM, Dean LS, Kapadia S, Cohen DJ,
Pichard AD, Szeto WY, Herrmann HC, Devireddy C, Leshnower BG,
Ailawadi G, Maniar HS, Hahn RT, Leon MB, Mack M. Outcomes in
nonagenarians undergoing transcatheter aortic valve replacement in the
PARTNER-I trial. Ann Thorac Surg 2015;100(3):785792.
Thourani VH, Suri RM, Gunter RL, Sheng S, OBrien SM, Ailawadi
G, Szeto WY, Dewey TM, Guyton RA, Bavaria JE, Babaliaros V, Gammie JS, Svensson L, Williams M, Badhwar V, Mack MJ. Contemporary
real-world outcomes of surgical aortic valve replacement in 141,905
low-risk, intermediate-risk, and high-risk patients. Ann Thorac Surg
2015;99(1):5561.
Titze N, Ivanukoff V, Fisher T, Pearl G, Grimsley B, Shutze WP.
Surgical repair of renal artery aneurysms. Proc (Bayl Univ Med Cent)
2015;28(4):499501.
Velazquez EJ, Samad Z, Al-Khalidi HR, Sangli C, Grayburn PA, Massaro
JM, Stevens SR, Feldman TE, Kruco MW. The MitraClip and survival
in patients with mitral regurgitation at high risk for surgery: a propensitymatched comparison. Am Heart J 2015;170(5):10501059.e3.
Verrier ED, Mack MJ. Viewpoint: transitions in cardiac surgery and interventional cardiologyteam mates or rivals? Heart 2015;101(5):346348.
Wang A, Sangli C, Lim S, Ailawadi G, Kar S, Herrmann HC, Grayburn
P, Foster E, Weissman NJ, Glower D, Feldman T. Evaluation of renal
function before and after percutaneous mitral valve repair. Circ Cardiovasc
Interv 2015;8(1).
Webb JG, Doshi D, Mack MJ, Makkar R, Smith CR, Pichard AD,
Kodali S, Kapadia S, Miller DC, Babaliaros V, Thourani V, Herrmann
HC, Bodenhamer M, Whisenant BK, Ramee S, Maniar H Jr, Kereiakes
D, Xu K, Jaber WA, Menon V, Tuzcu EM, Wood D, Svensson LG, Leon
MB. A randomized evaluation of the SAPIEN XT transcatheter heart
valve system in patients with aortic stenosis who are not candidates for
surgery. JACC Cardiovasc Interv 2015;8(14):17971806.
Wrobel K, Stevens SR, Jones RH, Selzman CH, Lamy A, Beaver TM,
Djokovic LT, Wang N, Velazquez EJ, Sopko G, Kron IL, DiMaio JM,
Michler RE, Lee KL, Yii M, Leng CY, Zembala M, Rouleau JL, Daly
RC, Al-Khalidi HR. Inuence of baseline characteristics, operative conduct, and postoperative course on 30-day outcomes of coronary artery
bypass grafting among patients with left ventricular dysfunction: results
from the Surgical Treatment for Ischemic Heart Failure (STICH) trial.
Circulation 2015;132(8):720730.
Yuan C, Lee HJ, Shin HJ, Stampfer MJ, Cho E. Fruit and vegetable
consumption and hypertriglyceridemia: Korean National Health and
Nutrition Examination Surveys (KNHANES) 20072009. Eur J Clin
Nutr 2015;69(11):11931199.
Zhang J, Ko JM, Guileyardo JM, Roberts WC. A review of spontaneous closure of ventricular septal defect. Proc (Bayl Univ Med Cent)
2015;28(4):516520.
Zhang YJ, Iqbal J, van Klaveren D, Campos CM, Holmes DR, Kappetein AP, Morice MC, Banning AP, Grech ED, Bourantas CV, Onuma
Y, Garcia-Garcia HM, Mack MJ, Colombo A, Mohr FW, Steyerberg
EW, Serruys PW. Smoking is associated with adverse clinical outcomes in
patients undergoing revascularization with PCI or CABG: the SYNTAX
trial at 5-year follow-up. J Am Coll Cardiol 2015;65(11):11071115.
Volume 29, Number 2
DERMATOLOGY
153. Aires DJ, Rockwell G, Menter A, Nielson C, Wick J, Sedivy S, Tawk
O, Bowcock A, Sinha AA. Reproducible novel transcriptional dierences between psoriatic lesional and non-lesional skin show increased
inammation and metabolism. J Drugs Dermatol 2015;14(8):794800.
154. Alikhan A, Grin JR, Newman CC. Use of Candida antigen injections
for the treatment of verruca vulgaris: a two-year Mayo Clinic experience.
J Dermatolog Treat 2015:14 [Epub ahead of print].
155. Ammar M, Jordan CT, Cao L, Lim E, Bouchlaka Souissi C, Jrad A,
Omrane I, Kouidhi S, Zaraa I, Anbunathan H, Mokni M, Doss N,
Guttman-Yassky E, El Gaaied B, Menter A, Bowcock AM. CARD14
alterations in Tunisian psoriasis patients and further characterization in
European cohorts. Br J Dermatol 2015 Sep 11 [Epub ahead of print].
156. Blome C, Costanzo A, Dauden E, Ferrandiz C, Girolomoni G, Gniadecki
R, Iversen L, Menter A, Michaelis-Wittern K, Morita A, Nakagawa H,
Reich K, Augustin M. Patient-relevant needs and treatment goals in nail
psoriasis. Qual Life Res 2015 Oct 3 [Epub ahead of print].
157. Campa M, Mansouri B, Warren R, Menter A. A review of biologic
therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque
psoriasis. Dermatol Ther (Heidelb) 2015 Dec 29 [Epub ahead of print].
158. Campa M, Ryan C, Menter A. An overview of developing TNF- targeted therapy for the treatment of psoriasis. Expert Opin Investig Drugs
2015;24(10):13431354.
159. Gottlieb AB, Kalb RE, Langley RG, Krueger GG, de Jong EM, Guenther
L, Goyal K, Fakharzadeh S, Chevrier M, Calabro S, Langhol W, Menter
A. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with iniximab and other systemic and biologic therapies. J Drugs Dermatol 2014;13(12):14411448.
160. Grin JR, Davis MD. Amitriptyline/ketamine as therapy for neuropathic pruritus and pain secondary to herpes zoster. J Drugs Dermatol
2015;14(2):115118.
161. Griths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter
A, Cameron GS, Erickson J, Zhang L, Secrest RJ, Ball S, Braun DK,
Osuntokun OO, Heernan MP, Nickolo BJ, Papp K; UNCOVER-2
and UNCOVER-3 investigators. Comparison of ixekizumab with
etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2
and UNCOVER-3): results from two phase 3 randomised trials. Lancet
2015;386(9993):541551.
162. Gupta AK, Daigle D, Abramovits W. Tavaborole 5% solution for onychomycosis. Skinmed 2015;13(1):5558.
163. Gupta AK, Daigle D, Abramovits W, Vincent KD. Xeljanz (tofacitinib)
for chronic plaque psoriasis. Skinmed 2015;13(3):227229.
164. Horner ME, Kourosh AS, Menter MA. Awareness and engagement in
political advocacy among dermatology residents: a needs assessment.
165. Kieliszak CR, Pollinger TH, Tollefson MM, Grin JR. Umbilical and
periumbilical dermatoses. J Am Acad Dermatol 2015;72(6):10661073.
166. Kimball AB, Rothman KJ, Kricorian G, Pariser D, Yamauchi PS, Menter
A, Teller CF, Aras G, Accortt NA, Hooper M, Rice KC, Gelfand JM.
OBSERVE-5: observational postmarketing safety surveillance registry of
etanercept for the treatment of psoriasis nal 5-year results. J Am Acad
Dermatol 2015;72(1):115122.
167. Kivelevitch DN, Menter A. Use of brodalumab for the treatment of
psoriasis and psoriatic arthritis. Immunotherapy 2015;7(4):323333.
168. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S,
Lalovic B, Aslanyan S, Wang EE, Hall D, Solinger A, Padula S, Scholl
P. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe
psoriasis: safety, ecacy, pharmacokinetics, and biomarker results of a
single-rising-dose, randomized, double-blind, placebo-controlled trial.
J Allergy Clin Immunol 2015 Mar 11.
169. Landells I, Marano C, Hsu MC, Li S, Zhu Y, Eicheneld LF, Hoeger
PH, Menter A, Paller AS, Taieb A, Philipp S, Szapary P, Randazzo B.
Ustekinumab in adolescent patients age 12 to 17 years with moderateto-severe plaque psoriasis: results of the randomized phase 3 CADMUS
study. J Am Acad Dermatol 2015;73(4):594603.
170. Langley RG, Rich P, Menter A, Krueger G, Goldblum O, Dutronc Y,
Zhu B, Wei H, Cameron GS, Heernan MP. Improvement of scalp and
April 2016
171.
172.
173.
174.
175.
176.
177.
178.
179.
180.
181.
182.
183.
184.
185.
186.
187.
188.
189.
190.
191.
192.
nail lesions with ixekizumab in a phase 2 trial in patients with chronic

plaque psoriasis. J Eur Acad Dermatol Venereol 2015;29(9):17631770.
Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp
K, Spelman L, Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB,
Bachelez H, Wu JJ, Crowley J, Langley RG, Blicharski T, Paul C, Lacour
JP, Tyring S, Kircik L, Chimenti S, Callis Dun K, Bagel J, Koo J, Aras
G, Li J, Song W, Milmont CE, Shi Y, Erondu N, Klekotka P, Kotzin B,
Nirula A. Phase 3 studies comparing brodalumab with ustekinumab in
psoriasis. N Engl J Med 2015;373(14):13181328.
Lim HW, Silpa-archa N, Amadi U, Menter A, Van Voorhees AS, Lebwohl
M. Phototherapy in dermatology: a call for action. J Am Acad Dermatol
2015;72(6):10781080.
Lloyd AA, Witheiler D, Menter A. Nodular fasciitis of the lip mucosa: a rare
but clinically important entity. Clin Exp Dermatol 2015;40(4):408412.
Mahmood T, Horner M, Menter A. Polymorphic blistering eruption and
stomatitis in a patient with non-Hodgkin lymphoma. JAMA Dermatol
2015;151(4):439440.
Mahmood T, Mansouri B, Menter A. Successful treatment of generalized granuloma annulare with adalimumab. Clin Exp Dermatol
2015;40(5):537539.
Mahmood T, Menter A. The Laugier-Hunziker syndrome. Proc (Bayl
Univ Med Cent) 2015;28(1):4142.
Mahmood T, Zaghi D, Menter A. Emerging oral drugs for psoriasis.
Expert Opin Emerg Drugs 2015:112.
Mansouri B, Horner ME, Menter A. Tumor necrosis factor- inhibitor
use in psoriasis patients with a rst-degree relative with multiple sclerosis.
J Drugs Dermatol 2015;14(8):876878.
Mansouri B, Kivelevitch D, Campa M, Menter A. Palmoplantar pustular
psoriasis unresponsive to the interleukin-1 antagonist canakinumab.
Clin Exp Dermatol 2015 Sep 7 [Epub ahead of print].
Mansouri B, Kivelevitch D. Re: Complete clinical remission of psoriasis 6
months after renal transplantation. Transplant Proc 2015;47(6):20742075.
Mansouri B, Menter A. Reporting of MABp1 for the treatment of psoriasis. JAMA Dermatol 2015;151(10):11431144.
Mansouri B, Richards L, Menter A. Treatment of two patients with generalized pustular psoriasis with the interleukin-1 inhibitor gevokizumab.
Br J Dermatol 2015;173(1):239241.
Mayer JE, Menter MA. Reply to: Review of drug-related causes of
oculocutaneous disease. J Am Acad Dermatol 2015;72(2):362363.
McFall MJ, Grin JR, Elston DM. A solitary auricular polyp. Indian
Dermatol Online J 2015;6(4):284285.
Menter A. Best practices: an oral treatment for moderate to severe plaque
psoriasis. Dermatology News Best Practices Supplement, October 22, 2015.
Menter A, Thai D, Papp KA, Wu JJ, Bereswill M, Teixeira HD, Rubant
S, Williams DA. Five-year analysis from the ESPRIT 10-year postmarketing surveillance registry of adalimumab treatment for moderate to severe
psoriasis. J Am Acad Dermatol 2015;73(3):410419.e6.
Menter MA, Griffiths CE. Psoriasis: the future. Dermatol Clin
2015;33(1):161166.
Menter MA, Griths CE. The International Psoriasis Council: advancing
knowledge, enhancing care. Dermatol Clin 2015;33(1):ixxii.
Navarrete-Dechent C, Majerson D, Torres M, Armijo D, Patel M, Menter
A, de la Cruz C. Use of tumor necrosis factor alpha (TNF ) antagonists in a patient with psoriasis and Chagas disease. An Bras Dermatol
2015;90(3 Suppl 1):171174.
Papp K, Menter A, Strober B, Kricorian G, Thompson EH, Milmont
CE, Nirula A, Klekotka P. Ecacy and safety of brodalumab in subpopulations of patients with dicult-to-treat moderate-to-severe plaque
psoriasis. J Am Acad Dermatol 2015;72(3):436439.e1.
Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB,
Langley R, Luger T, Thaci D, Buonanno M, Gupta P, Proulx J, Lan S,
Wolk R; OPT Pivotal 1 and OPT Pivotal 2 investigators. Tofacitinib, an
oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis:
results from two randomized, placebo-controlled, phase III trials. Br J
Dermatol 2015;173(4):949961.
Paul C, Bewley A, Girolomoni G, Reich K, Puig L, Lacour JP, Augustin
M, Naldi L, Menter AM, Wade S, Viswanathan HN, Palmer K, Klekotka
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194.
195.
196.
197.
198.
199.
200.
201.
P, Woolley JM. Real world skin clearance rates for biologic treatments in
patients with moderate to severe plaque psoriasis: interim results from
a large prospective, observational study. Value Health 2015;18(7):A429.
Richards LE, Horner ME, Menter A. Resident rounds part III: case
report: a papulo-nodular eruption with systemic signs and symptoms.
J Drugs Dermatol 2015;14(4):422.
Ryan C, Kirby B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol Clin 2015;33(1):4155.
Ryan C, Sadlier M, De Vol E, Patel M, Lloyd AA, Day A, Lally A,
Kirby B, Menter A. Genital psoriasis is associated with signicant impairment in quality of life and sexual functioning. J Am Acad Dermatol
2015;72(6):978983.
Scheinfeld N, Abramovits W, Gupta AK. Apremilast (Otezla). Skinmed
2015;13(5):381384.
Silverberg JI, Becker L, Kwasny M, Menter A, Cordoro KM, Paller AS.
Central obesity and high blood pressure in pediatric patients with atopic
dermatitis. JAMA Dermatol 2015;151(2):144152.
Soza GM, Grin JR. Acral vesicles and bullae in a patient with severe
rheumatoid arthritis. Proc (Bayl Univ Med Cent) 2015;28(4):461462.
Thompson AK, Peters MS, El-Azhary RA, Gibson LE, Chang MB, Grifn JR, Davis MD, McEvoy MT, Camilleri MJ, Bridges AG. Cutaneous
microemboli from hydrophilic polymer after endovascular procedures.
Tran C, Wilder E, Grin JR. Stomatitis, cutaneous bullae, and renal
failure. JAMA 2015;314(21):22962297.
Udovenko OV, Grin JR, Elston DM. Asymptomatic erythematous
plaque. Indian Dermatol Online J 2015;6(6):419421.
ENDOCRINOLOGY
Note: See also Transplantation for articles on islet cell transplantation.
202. Hollander P, King AB, Del Prato S, Sreenan S, Balci MK, MuozTorres M, Rosenstock J, Hansen CT, Niemeyer M, Garber AJ. Insulin degludec improves long-term glycaemic control similarly to insulin
glargine but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy. Diabetes Obes
Metab 2015;17(2):202206.
203. Hollander P, Sugimoto D, Vlajnic A, Kilo C. Combination therapy with
insulin glargine plus metformin but not insulin glargine plus sulfonylurea
provides similar glycemic control to triple oral combination therapy in
patients with type 2 diabetes uncontrolled with dual oral agent therapy.
J Diabetes Complications 2015;29(8):12661271.
204. Roe ED, Chamarthi B, Raskin P. Impact of bromocriptine-QR therapy
on glycemic control and daily insulin requirement in type 2 diabetes
mellitus subjects whose dysglycemia is poorly controlled on high-dose
insulin: a pilot study. J Diabetes Res 2015;2015:834903.
205. Rosenstock J, Hollander P, Bhargava A, Ilag LL, Pollom RK, Zielonka JS,
Huster WJ, Prince MJ. Similar ecacy and safety of LY2963016 insulin
glargine and insulin glargine (Lantus) in patients with type 2 diabetes
who were insulin-nave or previously treated with insulin glargine: a
randomized, double-blind controlled trial (the ELEMENT 2 study).
Diabetes Obes Metab 2015;17(8):734741.
206. Vora J, Seufert J, Solberg H, Kinduryte O, Johansen T, Hollander P.
Insulin degludec does not increase antibody formation versus insulin
glargine: an evaluation of phase 3a trials. Diabetes Obes Metab 2015
GASTROENTEROLOGY
Note: See also Oncology for research on colon cancer.
207. Betesh AL, Santa Ana CA, Cole JA, Fordtran JS. Is achlorhydria a cause
of iron deciency anemia? Am J Clin Nutr 2015;102(1):919.
208. Betesh AL, Santa Ana CA, Cole JA, Fordtran JS. Reply to R Schimann.
Am J Clin Nutr 2015;102(6):16151616.
209. Dassopoulos T, Cohen RD, Scherl EJ, Schwartz RM, Kosinski
L, Regueiro MD. Ulcerative colitis care pathway. Gastroenterology
2015;149(1):238245.
210. Huang C, Haritunians T, Okou DT, Cutler DJ, Zwick ME, Taylor
KD, Datta LW, Maranville JC, Liu Z, Ellis S, Chopra P, Alexander
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JS, Baldassano RN, Cross RK, Dassopoulos T, Dhere TA, Duerr RH,
Hanson JS, Hou JK, Hussain SZ, Isaacs KL, Kachelries KE, Kader H,
Kappelman MD, Katz J, Kellermayer R, Kirschner BS, Kuemmerle JF,
Kumar A, Kwon JH, Lazarev M, Mannon P, Moulton DE, Osuntokun
BO, Patel A, Rioux JD, Rotter JI, Saeed S, Scherl EJ, Silverberg MS,
Silverman A, Targan SR, Valentine JF, Wang MH, Simpson CL, Bridges
SL, Kimberly RP, Rich SS, Cho JH, Di Rienzo A, Kao LW, McGovern
DP, Brant SR, Kugathasan S. Characterization of genetic loci that affect susceptibility to inammatory bowel diseases in African Americans.
Gastroenterology 2015;149(6):15751586.
Kushnir VM, Oh YS, Hollander T, Chen CH, Sayuk GS, Davidson N,
Mullady D, Murad FM, Sharabash NM, Ruettgers E, Dassopoulos T,
Easler JJ, Gyawali CP, Edmundowicz SA, Early DS. Impact of retroexion vs. second forward view examination of the right colon on adenoma
detection: a comparison study. Am J Gastroenterol 2015;110(3):415422.
Lieberman D, Brill J, Canto M, DeMarco D, Fennerty B, Gupta N, Laine
L, Lightdale C, Montgomery E, Odze R, Rex D, Sharma P, Kochman M,
Tokar J. Management of diminutive colon polyps based on endoluminal
imaging. Clin Gastroenterol Hepatol 2015;13(11):18601866.
Moayyedi P, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR,
Soer EE, Spiegel BM, Ford AC. The eect of dietary intervention on
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Polter DE. Risk of colon perforation during colonoscopy at Baylor University Medical Center. Proc (Bayl Univ Med Cent) 2015;28(1):36.
Sharma P, Brill J, Canto M, DeMarco D, Fennerty B, Gupta N, Laine L,
Lieberman D, Lightdale C, Montgomery E, Odze R, Tokar J, Kochman
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Sorrentino D, Marino M, Dassopoulos T, Zari D, Del Bianco T. Low
dose iniximab for prevention of postoperative recurrence of Crohns
disease: long term follow-up and impact of iniximab trough levels and
antibodies to iniximab. PLoS One 2015;10(12):e0144900.
Yu C, Huo X, Agoston AT, Zhang X, Theiss AL, Cheng E, Zhang Q,
Zaika A, Pham TH, Wang DH, Lobie PE, Odze RD, Spechler SJ, Souza
RF. Mitochondrial STAT3 contributes to transformation of Barretts
epithelial cells that express oncogenic Ras in a p53-independent fashion.
Am J Physiol Gastrointest Liver Physiol 2015;309(3):G146G161.
Zhao Q, Mullin GE, Meng MQ, Dassopoulos T, Kumar R. A general
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222. Bennett M, Xiao Y. Relative risk of prolonged operative times from
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223. Couch C. Accountable: The Baylor Scott & White Quality Alliance Accountable Care Journey. Boca Raton, FL: CRC Press, 2015.
224. Couch C. Update on the Baylor Scott & White Quality Alliance. Proc
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225. Du Y, Wang X, Jack Lee J. Simulation study for evaluating the performance of response-adaptive randomization. Contemp Clin Trials
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226. Filardo G, et al. Quantitative systematic review. In Greenberg R, Daniel
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228. Goyal A, de Lemos JA, Peng SA, Thomas L, Amsterdam EA, Hockenberry JM, Peterson ED, Wang TY. Association of patient enrollment in
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229. Hazlehurst BL, Kurtz SE, Masica A, Stevens VJ, McBurnie MA, Puro
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230. Herrin J, da Graca B, Aponte P, Stanek HG, Cowling T, Fullerton C,
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231. Horwitz LI, Grady JN, Cohen DB, Lin Z, Volpe M, Ngo CK, Masica
AL, Long T, Wang J, Keenan M, Montague J, Suter LG, Ross JS, Drye
EE, Krumholz HM, Bernheim SM. Development and validation of an
algorithm to identify planned readmissions from claims data. J Hosp Med
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232. Horwitz LI, Masica AL, Auerbach AD. Introducing Choosing Wisely:
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233. Kennerly D. Learning by SWARMing adverse events. Jt Comm J Qual
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234. Masica AL, Collinsworth AW, Priest EL, Filardo G, Stauer BD, Smith
SH, Leveille MH, Houston S, Fleming NS, Ballard DJ. Health services
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235. Ogola GO, Gale SC, Haider A, Sha S. The nancial burden of emergency general surgery: national estimates 2010 to 2060. J Trauma Acute
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236. Overton TL, Phillips JL, Moore BJ, Campbell-Furtick MB, Gandhi RR,
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237. Savage SA, Klekar CS, Priest EL, Crandall ML, Rodriguez BC, Sha S;
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for emergency general surgery diseases. J Surg Res 2015;196(2):264269.
238. Sha S, Priest EL, Crandall ML, Klekar CS, Nazim A, Aboutanos M,
Agarwal S, Bhattacharya B, Byrge N, Dhillon TS, Eboli DJ, Fielder D,
Guillamondegui O, Gunter O, Inaba K, Mowery NT, Nirula R, Ross
SE, Savage SA, Schuster KM, Schmoker RK, Siboni S, Siparsky N,
Trust MD, Utter GH, Whelan J, Feliciano DV, Rozycki G. Multicenter
validation of American Association for the Surgery of Trauma grading
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Nutr 2015;102(6):1615.
Schimann R. Fabry disease. Handb Clin Neurol 2015;132:231248.
Schimann R. The consequences of genetic and pharmacologic reduction in sphingolipid synthesis. J Inherit Metab Dis 2015;38(1):7784.
Schimann R, Grishchuk Y, Goldin E. Mucolipidosis IV. In Pagon RA,
Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD,
Fong CT, Meord HC, Smith RJH, Stephens K, eds. GeneReviews
[Internet]. Seattle, WA: University of Washington, Seattle, 2015.
Schimann R, Swift C, Wang X, Blankenship D, Ries M. A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease. J Inherit Metab Dis
2015;38(6):11291136.
Shen JS, Busch A, Day TS, Meng XL, Yu CI, Dabrowska-Schlepp P, Fode
B, Niederkrger H, Forni S, Chen S, Schimann R, Frischmuth T, Schaaf
A. Mannose receptor-mediated delivery of moss-made -galactosidase
A eciently corrects enzyme deciency in Fabry mice. J Inherit Metab
Dis 2015 Aug 27 [Epub ahead of print].
Shen JS, Meng XL, Wight-Carter M, Day TS, Goetsch SC, Forni S,
Schneider JW, Liu ZP, Schimann R. Blocking hyperactive androgen
receptor signaling ameliorates cardiac and renal hypertrophy in Fabry
mice. Hum Mol Genet 2015;24(11):31813191.
Singhal NK, Li S, Arning E, Alkhayer K, Clements R, Sarcyk Z, Dassanayake RS, Brasch NE, Freeman EJ, Bottiglieri T, McDonough J.
Changes in methionine metabolism and histone H3 trimethylation
are linked to mitochondrial defects in multiple sclerosis. J Neurosci
2015;35(45):1517015186.
Strauss KA, Ferreira C, Bottiglieri T, Zhao X, Arning E, Zhang S, Zeisel
SH, Escolar ML, Presnick N, Puenberger EG, Vugrek O, Kovacevic L,
Wagner C, Mazariegos GV, Mudd SH, Soltys K. Liver transplantation
for treatment of severe S-adenosylhomocysteine hydrolase deciency.
Mol Genet Metab 2015;116(12):4452.
346. Vanderver A, Prust M, Tonduti D, Mochel F, Hussey HM, Helman G,

Garbern J, Eichler F, Labauge P, Aubourg P, Rodriguez D, Patterson MC,
Van Hove JL, Schmidt J, Wolf NI, Boespug-Tanguy O, Schimann R,
van der Knaap MS; GLIA Consortium. Case denition and classication of leukodystrophies and leukoencephalopathies. Mol Genet Metab
2015;114(4):494500.
347. Vogel KR, Ainslie GR, Phillips B, Arning E, Bottiglieri T, Shen DD,
Gibson KM. Physiological competition of brain phenylalanine accretion: initial pharmacokinetic analyses of aminoisobutyric and methylaminoisobutyric acids in Pahenu2-/- mice. Mol Genet Metab Rep
2015;3:8087.
348. Zigdon H, Savidor A, Levin Y, Meshcheriakova A, Schimann R, Futerman AH. Identication of a biomarker in cerebrospinal uid for neuronopathic forms of Gaucher disease. PLoS One 2015;10(3):e0120194.
NEPHROLOGY
Note: See also Cardiology for articles on the intersection of heart and kidney
function.
349. Akrawinthawong K, Ricci J, Cannon L, Dixon S, Kupfer K, Stivers D,
Alexander P, David S, McCullough PA. Subclinical and clinical contrastinduced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO),
a prospective study. Ren Fail 2015;37(2):187191.
350. Blough B, Moreland A, Mora A Jr. Metformin-induced lactic acidosis with emphasis on the anion gap. Proc (Bayl Univ Med Cent)
2015;28(1):3133.
351. Emmett M, Szerlip H. Approach to the adult with metabolic acidosis. In
Post TW, ed. UpToDate. Waltham, MA: UpToDate, 2015.
352. Emmett M, Szerlip H. Causes of lactic acidosis. In Post TW, ed. UpToDate. Waltham, MA: UpToDate, 2015.
353. Emmett M, Szerlip H. Clinical manifestations and evaluation of metabolic alkalosis. In Post TW, ed. UpToDate. Waltham, MA: UpToDate, 2015.
354. Parker TF 3rd, Arono GR. The medical director in integrated clinical
care models. Clin J Am Soc Nephrol 2015;10(7):12821286.
355. Szerlip HM. Acute renal failure. In Alguire PC, ed. Internal Medicine
Essentials for Clerkship Students, 4th ed. Philadelphia: American College
of Physicians, 2015.
356. Szerlip HM, Edwards ML, Williams BJ, Johnson LA, Vintimilla RM,
OBryant SE. Association between cognitive impairment and chronic kidney
disease in Mexican Americans. J Am Geriatr Soc 2015;63(10):20232028.
NEUROLOGY/NEUROSURGERY/SPINAL SURGERY
357. Afzal S, Recio M, Shamim S. Paraneoplastic cerebellar ataxia and the paraneoplastic syndromes. Proc (Bayl Univ Med Cent) 2015;28(2):217220.
358. Ames CP, Smith JS, Eastlack R, Blaskiewicz DJ, Sharey CI, Schwab
F, Bess S, Kim HJ, Mundis GM Jr, Klineberg E, Gupta M, OBrien
M, Hostin R, Scheer JK, Protopsaltis TS, Fu KM, Hart R, Albert TJ,
Riew KD, Fehlings MG, Deviren V, Lafage V; International Spine Study
Group. Reliability assessment of a novel cervical spine deformity classication system. J Neurosurg Spine 2015;23(6):673683.
359. Bess S, Line B, Fu KM, McCarthy I, Lafage V, Schwab F, Sharey C,
Ames C, Akbarnia B, Jo H, Kelly M, Burton D, Hart R, Klineberg E,
Kebaish K, Hostin R, Mundis G, Mummaneni P, Smith JS; International
Spine Study Group. The health impact of symptomatic adult spinal
deformity: comparison of deformity types to United States population
norms and chronic diseases. Spine (Phila Pa 1976) 2015 Oct 15 [Epub
ahead of print].
360. Fakurnejad S, Scheer JK, Lafage V, Smith JS, Deviren V, Hostin R,
Mundis GM Jr, Burton DC, Klineberg E, Gupta M, Kebaish K, Shaffrey CI, Bess S, Schwab F, Ames CP; International Spine Study Group.
The likelihood of reaching minimum clinically important dierence and
substantial clinical benet at 2 years following a 3-column osteotomy:
analysis of 140 patients. J Neurosurg Spine 2015;23(3):340348.
361. Gold R, Giovannoni G, Phillips JT, Fox RJ, Zhang A, Meltzer L, Kurukulasuriya NC. Ecacy and safety of delayed-release dimethyl fumarate
in patients newly diagnosed with relapsing-remitting multiple sclerosis
(RRMS). Mult Scler 2015;21(1):5766.
Volume 29, Number 2
362. Gold R, Phillips JT, Havrdova E, Bar-Or A, Kappos L, Kim N, Thullen

T, Valencia P, Oliva L, Novas M, Li J, Sweetser MT, Kurukulasuriya N,
Viglietta V, Fox RJ. Delayed-release dimethyl fumarate and pregnancy:
preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience. Neurol Ther 2015;4(2):93104.
363. Gupta MC, Ferrero E, Mundis G, Smith JS, Sharey CI, Schwab F,
Kim HJ, Boachie-Adjei O, Lafage V, Bess S, Hostin R, Burton DC,
Ames CP, Kebaish K, Klineberg E; International Spine Study Group.
Pedicle subtraction osteotomy in the revision versus primary adult spinal
deformity patient: is there a dierence in correction and complications?
Spine (Phila Pa 1976) 2015;40(22):E1169E1175.
364. Kappos L, Giovannoni G, Gold R, Phillips JT, Arnold DL, Hotermans
C, Zhang A, Viglietta V, Fox RJ; DEFINE and CONFIRM study
investigators. Time course of clinical and neuroradiological eects of
delayed-release dimethyl fumarate in multiple sclerosis. Eur J Neurol
2015;22(4):664671.
365. Liu S, Diebo BG, Henry JK, Smith JS, Hostin R, Cunningham ME,
Mundis G, Ames CP, Burton D, Bess S, Akbarnia B, Hart R, Passias
PG, Schwab FJ, Lafage V; International Spine Study Group (ISSG). The
benet of non-operative treatment for adult spinal deformity: identifying
predictors for reaching a minimal clinically important dierence. Spine
J 2015 Oct 31 [Epub ahead of print].
366. Miller DH, Fox RJ, Phillips JT, Hutchinson M, Havrdova E, Kita M,
Wheeler-Kingshott CA, Tozer DJ, MacManus DG, Yousry TA, Goodsell
M, Yang M, Zhang R, Viglietta V, Dawson KT; CONFIRM study investigators. Eects of delayed-release dimethyl fumarate on MRI measures
in the phase 3 CONFIRM study. Neurology 2015;84(11):11451152.
367. Oh T, Scheer JK, Eastlack R, Smith JS, Lafage V, Protopsaltis TS, Klineberg E, Passias PG, Deviren V, Hostin R, Gupta M, Bess S, Schwab
F, Sharey CI, Ames CP; International Spine Study Group. Cervical
compensatory alignment changes following correction of adult thoracic
deformity: a multicenter experience in 57 patients with a 2-year followup. J Neurosurg Spine 2015;22(6):658665.
368. Phillips JT, Selmaj K, Gold R, Fox RJ, Havrdova E, Giovannoni G,
Abourjaily H, Pace A, Novas M, Hotermans C, Viglietta V, Meltzer L.
Clinical signicance of gastrointestinal and ushing events in patients
with multiple sclerosis treated with delayed-release dimethyl fumarate.
Int J MS Care 2015;17(5):236243.
369. Scheer JK, Smith JS, Clark AJ, Lafage V, Kim HJ, Rolston JD, Eastlack
R, Hart RA, Protopsaltis TS, Kelly MP, Kebaish K, Gupta M, Klineberg E, Hostin R, Sharey CI, Schwab F, Ames CP; International Spine
Study Group. Comprehensive study of back and leg pain improvements
after adult spinal deformity surgery: analysis of 421 patients with 2-year
follow-up and of the impact of the surgery on treatment satisfaction.
J Neurosurg Spine 2015;22(5):540553.
370. Smith JS, Lafage V, Sharey CI, Schwab F, Lafage R, Hostin R, OBrien
M, Boachie-Adjei O, Akbarnia BA, Mundis GM, Errico T, Kim HJ,
Protopsaltis TS, Hamilton DK, Scheer JK, Sciubba D, Ailon T, Fu KG,
Kelly MP, Zebala L, Line B, Klineberg E, Gupta M, Deviren V, Hart R,
Burton D, Bess S, Ames CP; International Spine Study Group. Outcomes
of operative and nonoperative treatment for adult spinal deformity: a prospective, multicenter, propensity-matched cohort assessment with minimum 2-year follow-up. Neurosurgery 2015 Nov 16 [Epub ahead of print].
371. Smith JS, Ramchandran S, Lafage V, Sharey CI, Ailon T, Klineberg E,
Protopsaltis T, Schwab FJ, OBrien M, Hostin R, Gupta M, Mundis G,
Hart R, Kim HJ, Passias P, Scheer JK, Deviren V, Burton DC, Eastlack R,
Bess S, Albert TJ, Riew KD, Ames CP; International Spine Study Group.
Prospective multicenter assessment of early complication rates associated
with adult cervical deformity surgery in 78 patients. Neurosurgery 2015
372. Smith JS, Sharey CI, Lafage V, Schwab F, Scheer JK, Protopsaltis T,
Klineberg E, Gupta M, Hostin R, Fu KM, Mundis GM Jr, Kim HJ,
Deviren V, Soroceanu A, Hart RA, Burton DC, Bess S, Ames CP; International Spine Study Group. Comparison of best versus worst clinical
outcomes for adult spinal deformity surgery: a retrospective review of
a prospectively collected, multicenter database with 2-year follow-up.
J Neurosurg Spine 2015;23(3):349359.
April 2016
373. Soroceanu A, Burton DC, Diebo BG, Smith JS, Hostin R, Sharey CI,
Boachie-Adjei O, Mundis GM Jr, Ames C, Errico TJ, Bess S, Gupta MC,
Hart RA, Schwab FJ, Lafage V; International Spine Study Group. Impact
of obesity on complications, infection, and patient-reported outcomes
in adult spinal deformity surgery. J Neurosurg Spine 2015 Jul 31:19
374. Soroceanu A, Diebo BG, Burton D, Smith JS, Deviren V, Sharey
C, Kim HJ, Mundis G, Ames C, Errico T, Bess S, Hostin R, Hart R,
Schwab F, Lafage V; International Spine Study Group. Radiographical
and implant-related complications in adult spinal deformity surgery:
incidence, patient risk factors, and impact on health-related quality of
life. Spine (Phila Pa 1976) 2015;40(18):14141421.
375. Viglietta V, Miller D, Bar-Or A, Phillips JT, Arnold DL, Selmaj K, Kita
M, Hutchinson M, Yang M, Zhang R, Dawson KT, Sheikh SI, Fox
RJ, Gold R. Ecacy of delayed-release dimethyl fumarate in relapsingremitting multiple sclerosis: integrated analysis of the phase 3 trials. Ann
Clin Transl Neurol 2015;2(2):103118.
NURSING/ALLIED HEALTH
376. Dick TB, Moorman KL, MacDonald EA, Raines AA, Cox KD. Dening and implementing a model for pharmacy resident research projects.
Pharm Pract (Granada) 2015;13(3):562.
377. Hasse JM, DiCecco SR. Enteral nutrition in chronic liver disease: translating evidence into practice. Nutr Clin Pract 2015;30(4):474487.
378. Hull BL, Thut MC, Cheng SJ, Kaufhold DM, Brown SR. Changing the
culture of a large multihospital acute care therapy system to value-added
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379. Hussar DA, Jacob J. Edoxaban tosylate monohydrate, secukinumab, and
suvorexant. J Am Pharm Assoc 2015;55(5):563567.
380. Pack AE, Voskuhl GW. Anal cancer prevention in a high-risk population.
J Nurse Practit 2015;11(1):103108.
381. Pilcher J. A modied Delphi study to dene ah ha moments in education
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382. Pilcher J. eLearning and innovative learning options. J Nurs Prof Dev
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383. Pilcher J. Teaching nurses about research. Neonatal Netw 2015;34(1):4145.
384. Pilcher JW. Balancing innovation and evidence. J Nurs Prof Dev
2015;31(2):100105.
385. Reynolds J, Thibodeaux L, Jiang L, Francis K, Hochhalter A. Fit &
Strong! promotes physical activity and well-being in older cancer survivors. Front Public Health 2015;2:171.
386. Rothbauer J, Driver S, Callender L. Describing lymphedema in females
with Turner syndrome. Lymphology 2015;48(3):139152.
387. Sundin CS, Mazac LB. Implementing skin-to-skin care in the operating room after cesarean birth. MCN Am J Matern Child Nurs
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388. Tran HX, Herrington JD. Eect of ceftriaxone and cefepime on highdose methotrexate clearance. J Oncol Pharm Pract 2015 Sep 28 [Epub
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389. Winter M, Tjiong L. Does purposeful leader rounding make a dierence?
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OBSTETRICS/GYNECOLOGY
390. Dew L, Harris S, Yost N, Magee K, dePrisco G. Second trimester placenta percreta presenting as acute abdomen. Proc (Bayl Univ Med Cent)
2015;28(1):3840.
ONCOLOGY/HEMATOLOGY/SURGICAL ONCOLOGY/BONE MARROW
TRANSPLANTATION
391. Aapro M, Moebus V, Nitz U, OShaughnessy J, Pronzato P, Untch M,
Tomita D, Bohac C, Leyland-Jones B. Safety and ecacy outcomes
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meta-analysis. Ann Oncol 2015;26(4):688695.
392. Aapro M, Moebus V, Nitz U, OShaughnessy J, Pronzato P, Untch M,
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393. Adjei AA, Richards D, El-Khoueiry AB, Braiteh F, Becerra C, Stephenson

J, Hezel AF, Sherman M, Garbo LE, Lengwell DP, Iverson C, Miner
JN, Shen Z, Yeh LT, Gunawan S, Wilson DM, Manhard KJ, Rajagopalan
P, Krissel H, Clendeninn NJ. A phase I study of the safety, pharmacokinetics, and pharmacodynamics of combination therapy with refametinib
plus sorafenib in patients with advanced cancer. Clin Cancer Res 2015
394. Agarwal S, Gincherman M, Birnbaum E, Fleshman JW, Mutch M. Comparison of long-term follow up of laparoscopic versus open colectomy for
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395. Antelo M, Milito D, Rhees J, Roca E, Barugel M, Cuatrecasas M, Moreira
L, Leoz ML, Carballal S, Ocana T, Pellise M, Castells A, Boland CR,
Goel A, Balaguer F. Pitfalls in the diagnosis of biallelic PMS2 mutations.
Familial Cancer 2015;14(3):411414.
396. Avis NE, Levine BJ, Case LD, Naftalis EZ, Van Zee KJ. Trajectories of
depressive symptoms following breast cancer diagnosis. Cancer Epidemiol
Biomarkers Prev 2015;24(11):17891795.
397. Aznar N, Midde KK, Dunkel Y, Lopez-Sanchez I, Pavlova Y, Marivin
A, Barbazn J, Murray F, Nitsche U, Janssen KP, Willert K, Goel A,
Abal M, Garcia-Marcos M, Ghosh P. Daple is a novel non-receptor
GEF required for trimeric G protein activation in Wnt signaling. Elife
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398. Bachanova V, Burns LJ, Ahn KW, Laport GG, Akpek G, Kharfan-Dabaja
MA, Nishihori T, Agura E, Armand P, Jaglowski SM, Cairo MS, Cashen
AF, Cohen JB, DSouza A, Freytes CO, Gale RP, Ganguly S, Ghosh
N, Holmberg LA, Inwards DJ, Kanate AS, Lazarus HM, Malone AK,
Munker R, Mussetti A, Norkin M, Prestidge TD, Rowe JM, Satwani
P, Siddiqi T, Sti PJ, William BM, Wirk B, Maloney DG, Smith SM,
Sureda AM, Carreras J, Hamadani M; Center for International Blood
and Marrow Transplant Research Lymphoma Working Committee. Impact of pretransplantation (18)F-uorodeoxy glucose-positron emission
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2015;21(9):16051611.
399. Barve M, Wang Z, Kumar P, Jay CM, Luo X, Bedell C, Mennel RG,
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400. Boland CR. Cancer Family: The Search for the Cause of Hereditary Colorectal Cancer. Bloomington, IN: AuthorHouse Publishers, 2015.
401. Boland BS, Widjaja CE, Banno A, Zhang B, Kim SH, Stoven S, Peterson
MR, Jones MC, Su HI, Crowe SE, Bui JD, Ho SB, Okugawa Y, Goel A,
Marietta EV, Khosroheidari M, Jepsen K, Aramburu J, Lpez-Rodrguez
C, Sandborn WJ, Murray JA, Harismendy O, Chang JT. Immunodeciency and autoimmune enterocolopathy linked to NFAT5 haploinsufciency. J Immunol 2015;194(6):25512560.
402. Boyle FM, Smith IE, OShaughnessy J, Ejlertsen B, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard
KI, Lindquist D, Amonkar M, Huang Y, Rappold E, Williams LS, WangSilvanto J, Kaneko T, Finkelstein DM, Goss PE; TEACH Investigators.
Health related quality of life of women in TEACH, a randomised placebo
controlled adjuvant trial of lapatinib in early stage human epidermal
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403. Buhrmann C, Shayan P, Kraehe P, Popper B, Goel A, Shakibaei M.
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404. Campa-Thompson M, Weir R, Calcetera N, Quirke P, Carmack S. Pathologic processing of the total mesorectal excision. Clin Colon Rectal Surg
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405. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov
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Borgman-Hagey A, Hessel C, Scheold C, Schwab GM, Tannir NM,
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406. Corr BR, Finlay-Schultz J, Rosen RB, Qamar L, Post MD, Behbakht
K, Spillman MA, Sartorius CA. Cytokeratin 5-positive cells represent a
therapy resistant subpopulation in epithelial ovarian cancer. Int J Gynecol
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407. Danhauer SC, Russell G, Case LD, Sohl SJ, Tedeschi RG, Addington
EL, Triplett K, Van Zee KJ, Naftalis EZ, Levine B, Avis NE. Trajectories
of posttraumatic growth and associated characteristics in women with
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408. Divers J, OShaughnessy J. Stomatitis associated with use of mTOR
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409. Early Breast Cancer Trialists Collaborative Group [OShaughnessy J],
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D, Evans V, Pan H, Peto R, Bradley R, Gray R. Adjuvant bisphosphonate
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410. Early Breast Cancer Trialists Collaborative Group [OShaughnessy J],
Dowsett M, Forbes JF, Bradley R, Ingle J, Aihara T, Bliss J, Boccardo
F, Coates A, Coombes RC, Cuzick J, Dubsky P, Gnant M, Kaufmann
M, Kilburn L, Perrone F, Rea D, Thrlimann B, van de Velde C, Pan
H, Peto R, Davies C, Gray R. Aromatase inhibitors versus tamoxifen in
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411. Endicott-Yazdani T, Ghazi A, Armstrong D, Guileyardo J, Schuller D.
Fatal pulmonary tumor thrombotic microangiopathy caused by undiagnosed metastatic gastric adenocarcinoma. Proc (Bayl Univ Med Cent)
2015;28(4):482483.
412. Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M,
Peters WR Jr, Maun D, Chang G, Herline A, Fichera A, Mutch M,
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Marcello P, Posner M, Read T, Monson J, Wren SM, Pisters PW, Nelson
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413. Ghisoli M, Barve M, Schneider R, Mennel R, Lenarsky C, Wallraven G,
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414. Goel A. MicroRNAs as therapeutic targets in colitis and colitisassociated cancer: tiny players with a giant impact. Gastroenterology
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415. Goodenberger ML, Kotsopoulos J, Lubinski J, Gronwald J, Cybulski C,
Demsky R, Neuhausen SL, Kim-Sing C, Tung N, Friedman S, Senter L,
Weitzel J, Karlan B, Moller P, Sun P, Narod SA; the Hereditary Breast
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of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Int J Cancer
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416. Goodenberger ML, Thomas BC, Riegert-Johnson D, Boland CR, Plon
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417. Graham RL, Mardones MA, Krause JR. Primary follicular lymphoma
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418. Grant MD. Cannula-assisted ap elevation (CAFE): a novel technique
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419. Gronwald J, Glass K, Rosen B, Karlan B, Tung N, Neuhausen SL, Moller
P, Ainsworth P, Sun P, Narod SA, Lubinski J, Kotsopoulos J; Hereditary
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420. Guy MS, Qamar L, Behbakht K, Post MD, Sheeder J, Sartorius CA,
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Hakiman H, Pendola M, Fleshman JW. Replacing transanal excision with
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placebo-controlled phase II trial of the Sarah Cannon Research Institute.
Breast Cancer Res Treat 2015;154(1):8997.
Yardley DA, Brufsky A, Coleman RE, Conte PF, Cortes J, Glck S,
Nabholtz JM, OShaughnessy J, Beck RM, Ko A, Renschler MF, Barton D, Harbeck N. Phase II/III weekly nab-paclitaxel plus gemcitabine
or carboplatin versus gemcitabine/carboplatin as rst-line treatment of
253
510.
511.
512.
513.
patients with metastatic triple-negative breast cancer (the tnAcity study):

study protocol for a randomized controlled trial. Trials 2015;16(1):575.
Young CD, Zimmerman LJ, Hoshino D, Formisano L, Hanker AB, Gatza
ML, Morrison MM, Moore PD, Whitwell CA, Dave B, Stricker T, Bhola
NE, Silva GO, Patel P, Brantley-Sieders DM, Levin M, Horiates M, Palma NA, Wang K, Stephens PJ, Perou CM, Weaver AM, OShaughnessy
JA, Chang JC, Park BH, Liebler DC, Cook RS, Arteaga CL. Activating
PIK3CA mutations induce an epidermal growth factor receptor (EGFR)/
extracellular signal-regulated kinase (ERK) paracrine signaling axis in
basal-like breast cancer. Mol Cell Proteomics 2015;14(7):19591976.
Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland
SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner
GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized
multicenter phase II study of avopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica 2015;100(9):11721179.
Zumwalt TJ, Arnold M, Goel A, Boland CR. Active secretion of CXCL10
and CCL5 from colorectal cancer microenvironments associates with
GranzymeB+ CD8+ T-cell inltration. Oncotarget 2015;6(5):29812991.
Zumwalt TJ, Goel A. Immunotherapy of metastatic colorectal cancer:
prevailing challenges and new perspectives. Curr Colorectal Cancer Rep
2015;11(3):125140.
OPHTHALMOLOGY
514. Scholl HP, Moore AT, Koenekoop RK, Wen Y, Fishman GA, van den
Born LI, Bittner A, Bowles K, Fletcher EC, Collison FT, Dagnelie G,
Degli Eposti S, Michaelides M, Saperstein DA, Schuchard RA, Barnes
C, Zein W, Zobor D, Birch DG, Mendola JD, Zrenner E; RET IRD
01 Study Group. Safety and proof-of-concept study of oral QLT091001
in retinitis pigmentosa due to inherited deciencies of retinal pigment
epithelial 65 protein (RPE65) or lecithin:retinol acyltransferase (LRAT).
PLoS One 2015;10(12):e0143846.
515. Starks VS, Gilliland G, Hise J, Thacker I, Layton KL. Eect of resection
of an orbital arteriovenous malformation on central venous pressure. Proc
516. Tullis BE, Ryals RC, Coyner AS, Gale MJ, Nicholson A, Ku C, Regis D,
Sinha W, Datta S, Wen Y, Yang P, Pennesi ME. Sarpogrelate, a 5-HT2A
receptor antagonist, protects the retina from light-induced retinopathy.
Invest Ophthalmol Vis Sci 2015;56(8):45604569.
ORAL AND MAXILLOFACIAL SURGERY
517. Carmichael RA, Kang DR. Frontal sinus mucopyocele presenting as a subcutaneous forehead mass. J Oral Maxillofac Surg 2015;73(11):21552161.
518. Ferreira L, Jham B, Assi R, Readinger A, Kessler HP. Oral melanocytic
nevi: a clinicopathologic study of 100 cases. Oral Surg Oral Med Oral
Pathol Oral Radiol 2015;120(3):358367.
519. Gomes LR, Gomes M, Jung B, Paniagua B, Ruellas AC, Gonalves JR,
Styner MA, Wolford L, Cevidanes L. Diagnostic index of 3D osteoarthritic changes in TMJ condylar morphology. Proc SPIE Int Soc Opt
Eng 2015;9414.
520. Gonalves JR, Cassano DS, Rezende L, Wolford LM. Disc repositioning:
does it really work? Oral Maxillofac Surg Clin North Am 2015;27(1):85107.
521. Kovach TA, Kang DR, Triplett RG. Massive macroglossia secondary to
angioedema: a review and presentation of a case. J Oral Maxillofac Surg
2015;73(5):905917.
522. Movahed R, Wolford LM. Protocol for concomitant temporomandibular
joint custom-tted total joint reconstruction and orthognathic surgery
using computer-assisted surgical simulation. Oral Maxillofac Surg Clin
North Am 2015;27(1):3745.
523. Perez DE, Wolford LM. Contemporary management of temporomandibular joint disorders. Oral Maxillofac Surg Clin North Am 2015;27(1):ix.
524. Rodrigues DB, Wolford LM, Malaquias P, Campos PS. Concomitant
treatment of mandibular ameloblastoma and bilateral temporomandibular joint osteoarthritis with bone graft and total joint prostheses. J Oral
Maxillofac Surg 2015;73(1):6374.
525. Salash JR, Hossameldin RH, Almarza AJ, Chou JC, McCain JP, Mercuri LG, Wolford LM, Detamore MS. Potential indications for tissue
254
526.
527.
528.
529.
engineering in temporomandibular joint surgery. J Oral Maxillofac Surg

2015 Nov 19 [Epub ahead of print].
Wolford LM. Inuence of osteotomy design on bilateral mandibular ramus
sagittal split osteotomy. J Oral Maxillofac Surg 2015;73(10):19942004.
Wolford LM, Gonalves JR. Condylar resorption of the temporomandibular joint: how do we treat it? Oral Maxillofac Surg Clin North Am
2015;27(1):4767.
Wolford LM, Mercuri LG, Schneiderman ED, Movahed R, Allen W.
Twenty-year follow-up study on a patient-tted temporomandibular joint
prosthesis: the Techmedica/TMJ Concepts device. J Oral Maxillofac Surg
2015;73(5):952960.
Wolford LM, Perez DE. Surgical management of congenital deformities
with temporomandibular joint malformation. Oral Maxillofac Surg Clin
North Am 2015;27(1):137154.
ORTHOPEDIC SURGERY
530. Amar E, Warschawski Y, Sharfman ZT, Martin HD, Safran MR, Rath
E. Pathological ndings in patients with low anterior inferior iliac spine
impingement. Surg Radiol Anat 2015 Nov 30 [Epub ahead of print].
531. Bariteau JT, Murillo DM, Tenenbaum SA, Brodsky JW. Joint salvage
after neglected intra-articular physeal fracture of the hallux in high-level
gymnasts. Foot Ankle Spec 2015;8(2):130134.
532. Chao J, Choi JH, Grear BJ, Tenenbaum S, Bariteau JT, Brodsky JW.
Early radiographic and clinical results of Salto total ankle arthroplasty
as a xed-bearing device. Foot Ankle Surg 2015;21(2):9196.
533. Davis JA, Hogan C, Dayton M. Postoperative coronal alignment after
total knee arthroplasty: does tailoring the femoral valgus cut angle really
matter? J Arthroplasty 2015;30(8):14441448.
534. Flanagin BA, Lindskog DM. Intraoperative radiofrequency ablation for
osteoid osteoma. Am J Orthop (Belle Mead NJ) 2015;44(3):127130.
535. Garofalo R, Flanagin B, Castagna A, Lo EY, Krishnan SG. Long stem
reverse shoulder arthroplasty and cerclage for treatment of complex long
segment proximal humeral fractures with diaphyseal extension in patients
more than 65 years old. Injury 2015;46(12):23792383.
536. Garofalo R, Flanagin B, Castagna A, Lo EY, Krishnan SG. Reverse shoulder arthroplasty for proximal humerus fracture using a dedicated stem:
radiological outcomes at a minimum 2 years of follow-up-case series.
J Orthop Surg Res 2015;10:129.
537. Gmez-Hoyos J, Reddy M, Martin HD. Dry endoscopic-assisted miniopen approach with neuromonitoring for chronic hamstring avulsions
and ischial tunnel syndrome. Arthrosc Tech 2015;4(3):e193e199.
538. Gmez-Hoyos J, Schrder RG, Reddy M, Palmer IJ, Khoury A, Martin
HD. The relationship of psoas impingement with increased lesser trochanteric retroversion. J Hip Pres Surg 2015;2(2):164169.
539. Gmez-Hoyos J, Schrder RG, Reddy MP, Khoury A, Palmer IJ, Martin
HD. Iliopsoas tendon insertion footprint with surgical implication in
lesser trochanterplasty for treating ischiofemoral impingement: an anatomic study. J Hip Pres Surg 2015(Nov):17.
540. Gmez-Hoyos J, Schrder RG, Reddy MP, Palmer IJ, Martin HD. Femoral neck anteversion and lesser trochanteric retroversion in patients with
ischiofemoral impingement: a case-control MRI study. Arthroscopy 2015
Sept 7 [Epub ahead of print].
541. Hatem M, Palmer IJ, Martin HD. Diagnosis and 2-year outcomes
of endoscopic treatment for ischiofemoral impingement. Arthroscopy
2015;31(2):239246.
542. Hatem M, Schrder RG, Reddy MP, Toye L, Gmez-Hoyos J, Martin
HD. A MRI study of lesser trochanteric version and its relationship to
proximal femoral osseous anatomy. J Hip Pres Surg 2015 Nov 9 [Epub
ahead of print].
543. Krishnan SG, Garofalo R, Flanagin B, Castagna A. Intramedullary
clavicle xation with single large fragmentary screw. Musculoskelet Surg
2015;99(Suppl 1):S25S30.
544. Mrquez WH, Arias LF, Martin HD, Gmez-Hoyos J. Surgical and histologic conrmation of psoas regeneration after arthroscopic tenotomy.
Arthroscopy 2015;31(7):12211222.
545. Martin H. Endoscopy of the deep gluteal space. In Guanche C, Byrd
JWT, eds. Advanced Hip Arthroscopy. Philadelphia: Elsevier, 2015.
Volume 29, Number 2
546. Martin HD, ed. Mini symposium: evolving concepts in extra-articular

hip pathology. J Hip Pres Surg 2015;2(2):91122.
547. Martin H, Palmer IJ, Hatem MA. Deep gluteal space syndrome. In Nho
S, Leuning M, Kelly B, Bedi A, Larson C, eds., Hip Arthroscopy and Hip
Joint Preservation Surgery. New York: Springer, 2015.
548. Martin H, Palmer IJ, Hatem MA. Physical examination of the hip. In
Nho S, Leuning M, Kelly B, Bedi A, Larson C, eds., Hip Arthroscopy and
Hip Joint Preservation Surgery. New York: Springer, 2015.
549. Martin H, Palmer IJ, Hatem MA. Surgical technique: endoscopic sciatic
nerve release. In Nho S, Leuning M, Kelly B, Bedi A, Larson C, eds., Hip
Arthroscopy and Hip Joint Preservation Surgery. New York: Springer, 2015.
550. Martin HD, Larson CM, Trousdale RT. Orthopedic round table: panel
discusses new types and treatments of hip impingement. Orthopedics
Today, May 2015.
551. Martnez D, Gmez-Hoyos J, Mrquez W, Gallo J. Factors associated
with the failure of arthroscopic surgery treatment in patients with femoroacetabular impingement: a cohort study. Rev Esp Cir Ortop Traumatol
2015;59(2):112121.
552. Tenenbaum S, Stockton KG, Bariteau JT, Brodsky JW. Salvage of avascular necrosis of the talus by combined ankle and hindfoot arthrodesis
without structural bone graft. Foot Ankle Int 2015;36(3):282287.
566.
567.
568.
569.
570.
571.
572.
OTOLARYNGOLOGY
553. Chan D, Ducic Y. A simplied, reliable approach for advancement genioplasty. JAMA Facial Plast Surg 2015 Dec 23 [Epub ahead of print].
554. Ducic Y. Intraoperative free ap monitoring using indocyanine green.
JAMA Facial Plast Surg 2015;17(6):427.
555. Gordin E, Lee TS, Ducic Y, Arnaoutakis D. Facial nerve trauma: evaluation and considerations in management. Craniomaxillofac Trauma Reconstr 2015;8(1):113.
556. Kadakia S, Ducic Y, Marra D, Saman M. The role of elective supercial parotidectomy in the treatment of temporal region squamous cell
carcinoma. Oral Maxillofac Surg 2015 Dec 21 [Epub ahead of print].
557. Kadakia S, Saman M, Gordin E, Marra D, Ducic Y. The role of parotidectomy in the treatment of auricular squamous cell carcinoma. Otolaryngol
Head Neck Surg 2015;152(6):10481052.
558. Mourad M, Saman M, Ducic Y. Internal to external jugular vein bypass
allowing for simultaneous bilateral radical neck dissection. Laryngoscope
2015;125(11):24802484.
559. Mourad M, Saman M, Sawhney R, Ducic Y. Management of the thyroid
gland during total laryngectomy in patients with laryngeal squamous cell
carcinoma. Laryngoscope 2015;125(8):18351838.
560. Mourad M, Saman M, Stroman D, Lee T, Ducic Y. Carotid artery sacrice and reconstruction in the setting of advanced head and neck cancer.
Otolaryngol Head Neck Surg 2015;153(2):225230.
561. Saman M, Kadakia S, Ducic Y. Does the use of an acellular dermal graft
in abdominal closure after rectus ap harvest impact the occurrence of
post-operative hernia? Oral Maxillofac Surg 2015;19(4):347351.
PATHOLOGY
Note: See also Oncology and other departments in which pathologists were rst
authors or coauthors.
562. Armstrong-Briley D, Hozhabri NST, Armstrong K, Puthottile J, Benavides R, Beal S. Comparison of length of stay and outcomes of patients
with positive versus negative blood culture results. Proc (Bayl Univ Med
Cent) 2015;28(1):1013.
563. Atta MG, Estrella MM, Skorecki KL, Kopp JB, Winkler CA, Wasser
WG, Shemer R, Racusen LC, Kuperman M, Foy MC, Lucas GM, Fine
DM. Association of APOL1 genotype with renal histology among black
HIV-positive patients undergoing kidney biopsy. Clin J Am Soc Nephrol
2015 Dec 14 [Epub ahead of print].
564. Beal SG, Thomas C, Dhiman N, Nguyen D, Qin H, Hawkins JM,
Dekmezian M, Benavides R, Njoku J. Antibiotic utilization improvement
with the Nanosphere Verigene Gram-Positive Blood Culture assay. Proc
565. Dekmezian M, Beal SG, Damashek MJ, Benavides R, Dhiman N. The
SUCCESS model for laboratory performance and execution of rapid
April 2016
molecular diagnostics in patients with sepsis. Proc (Bayl Univ Med Cent)
2015;28(2):144150.
Guileyardo JM. Probability and uncertainty in clinical and forensic medicine. Proc (Bayl Univ Med Cent) 2015;28(2):247249.
Kang X, Hu DY, Li CB, Li XH, Fan SL, Liu Y, Tang GY, Ai ZS, Wu T,
Mohan C, Zhou XJ, Liu JY, Peng A. The volume ratio of ground glass
opacity in early lung CT predicts mortality in acute paraquat poisoning.
PLoS One 2015;10(4):e0121691.
Podduturi V, Guileyardo JM. Sickle cell trait as a contributory cause of
death in natural disease. J Forensic Sci 2015;60(3):807811.
Podduturi V, Guileyardo JM, Soto LR, Krause JR. A case series of clinically undiagnosed hematopoietic neoplasms discovered at autopsy. Am
J Clin Pathol 2015;143(6):854860.
Podduturi V, Tran T, Champion KJ, Onur N, Shiller SM. Microcystic
stromal tumor of the ovary: a case report of a newly described ovarian
neoplasm with a -catenin (CTNNB1) G34E mutation. Int J Gynecol
Pathol 2015;34(6):541545.
Rauhauser AA, Ren C, Lu D, Li B, Zhu J, McEnery K, Vadnagara K,
Zepeda-Orozco D, Zhou XJ, Lin F, Jetten AM, Attanasio M. Hedgehog
signaling indirectly aects tubular cell survival after obstructive kidney
injury. Am J Physiol Renal Physiol 2015;309(9):F770F778.
Ye T, Zhen J, Du Y, Zhou JK, Peng A, Vaziri ND, Mohan C, Xu Y,
Zhou XJ. Green tea polyphenol-epigallocatechin-3-gallate restores
Nrf2 activity and ameliorates crescentic glomerulonephritis. PLoS One
2015;10(3):e0119543.
PEDIATRICS/NEONATOLOGY
573. Chiruvolu A, Tolia VN, Qin H, Stone GL, Rich D, Conant RJ, Inzer
RW. Eect of delayed cord clamping on very preterm infants. Am J Obstet
Gynecol 2015;213(5):676.e17.
574. Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies
of NICU deaths. Pediatrics 2015;135(1):e59e65.
575. Patel SD, Pierce L, Ciardiello A, Hutton A, Paskewitz S, Aronowitz
E, Voss HU, Moore H, Vannucci SJ. Therapeutic hypothermia and
hypoxia-ischemia in the term-equivalent neonatal rat: characterization
of a translational preclinical model. Pediatr Res 2015;78(3):264271.
576. Tolia VN, Patrick SW, Bennett MM, Murthy K, Sousa J, Smith PB, Clark
RH, Spitzer AR. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med 2015;372(22):21182126.
577. Tower P, Tolia VN. Another preemie with hypoglycemia? BeckwithWiedemann syndromea case study. Neonatal Netw 2015;34(3):178182.
PULMONOLOGY
578. Modrykamien AM, Gupta P. The acute respiratory distress syndrome.
579. Mora A Jr. The masquerading pulmonary embolism: why a high index of
suspicion remains even today. Proc (Bayl Univ Med Cent) 2015;28(1):71.
580. Mora A Jr, Arroyo M, Gummelt KL, Colbert G, Ursales AL, Van Vrancken MJ, Snipes GJ, Guileyardo JM, Columbus C. West Nile virus and the
2012 outbreak: the Baylor University Medical Center experience. Proc
581. Rokadia HK, Adams JR, McCarthy K, Aboussouan LS, Mireles-Cabodevila E. Cough augmentation in a patient with neuromuscular disease.
Ann Am Thorac Soc 2015;12(12):18881891.
582. Russo R, Coultas D, Ashmore J, Peoples J, Sloan J, Jackson BE, Uhm M,
Singh KP, Blair SN, Bae S. Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment
and baseline patient characteristics. Contemp Clin Trials 2015;41:192201.
583. Schuller D. Lung abscess. In Bope ET, Kellerman RD, eds. Conns Current
Therapy 2015, 67th ed. Philadelphia: Elsevier, 2015:401403.
RADIOLOGY
Note: See also Oncology and other departments in which radiologists were rst
authors or coauthors.
584. Bahador FM, Lati HR, Grossman SJ, Oza UD, Xu H, Grieth LK.
Optimal interpretative strategy for preoperative parathyroid scintigraphy.
Clin Nucl Med 2015;40(2):116122.
255
585. Bell BM Jr, Bruner A, Landaverde C, Rees CR. Prone positioning for transjugular intrahepatic portosystemic shunt revision to prevent exacerbation
of existing radiation dermatitis. J Vasc Interv Radiol 2015;26(5):764765.
586. Bell BM Jr, Cura M, Shaw CJ, Rees CR. Transjugular intrahepatic portosystemic shunt creation using a three-dimensional uoroscopy guidance
system in patients with the Budd-Chiari syndrome. Proc (Bayl Univ Med
Cent) 2015;28(4):484487.
587. dePrisco G. MRI local staging and restaging in rectal cancer. Clin Colon
Rectal Surg 2015;28(3):194200.
588. Evans AJ, Kip KE, Brinjikji W, Layton KF, Jensen ML, Gaughen JR,
Kallmes DF. Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures. J Neurointerv
Surg 2015 Jun 24 [Epub ahead of print].
589. Mason C, Yokubaitis K, Howard E, Shah Z, Wang J. Impact of Hendas
law on the utilization of screening breast magnetic resonance imaging.
590. Weir VJ, Zhang J, Bruner AP. Dosimetric characterization and image
quality evaluation of the AIRO mobile CT scanner. J Xray Sci Technol
2015;23(3):373381.
591. West JA, Louis TH. Radiographic ndings in the nail-patella syndrome.
RHEUMATOLOGY
592. Bykerk VP, Cush J, Winthrop K, Calabrese L, Lortholary O, de
Longueville M, van Vollenhoven R, Mariette X. Update on the safety
prole of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials. Ann Rheum Dis 2015;74(1):96103.
593. Clowse ME, Wolf DC, Frger F, Cush JJ, Golembesky A, Shaughnessy
L, De Cuyper D, Mahadevan U. Pregnancy outcomes in subjects exposed
to certolizumab pegol. J Rheumatol 2015;42(12):22702278.
594. Dalal DS, Lin YC, Brennan DM, Borkar N, Korman N, Husni ME.
Quantifying harmful eects of psoriatic diseases on quality of life: cardiometabolic outcomes in psoriatic arthritis study (COMPASS). Semin
Arthritis Rheum 2015;44(6):641645.
595. Kavanaugh A, Cush JJ. Pregnancy: data, outcomes, and treatment paradigms in rheumatology. J Rheumatol 2015;42(8):13571358.
596. Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, Clowse M, Curtis JR, Dao K, Hankins GD, Koren G, Kim
SC, Lapteva L, Mahadevan U, Moore T, Nolan M, Ren Z, Sammaritano LR, Seymour S, Weisman MH. Proceedings from the American
College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inammatory diseases. Arthritis Care Res (Hoboken)
2015;67(3):313325.
SURGERY
Note: Most surgery articles are subclassied by specialty, even if general surgeons were
rst authors or coauthors. Surgery articles related to cancer appear under Oncology.
597. Argun OB, Chrouser K, Chauhan S, Monga M, Knudsen B, Box GN,
Lee DI, Gettman MT, Poniatowski LH, Wang Q, Reihsen TE, Sweet
RM. Multi-institutional validation of an OSATS for the assessment of
cystoscopic and ureteroscopic skills. J Urol 2015;194(4):10981105.
598. Gardner AK, Willis RE, Dunkin BJ, Van Sickle KR, Brown KM, Truitt
MS, Uecker JM, Gentry L, Scott DJ. What do residents need to be
competent laparoscopic and endoscopic surgeons? Surg Endosc 2015 Oct
20 [Epub ahead of print].
599. Graziano K, Islam S, Dasgupta R, Lopez ME, Austin M, Chen LE,
Goldin A, Downard CD, Renaud E, Abdullah F. Asymptomatic malrotation: diagnosis and surgical management: an American Pediatric
Surgical Association Outcomes and Evidence Based Practice Committee
systematic review. J Pediatr Surg 2015;50(10):17831790.
600. King DR, Li W, Squiers JJ, Mohan R, Sellke E, Mo W, Zhang X, Fan
W, DiMaio JM, Thatcher JE. Surgical wound debridement sequentially
characterized in a porcine burn model with multispectral imaging. Burns
2015;41(7):14781487.
601. Perez M, Xu S, Chauhan S, Tanaka A, Simpson K, Abdul-Muhsin H,
Smith R. Impact of delay on telesurgical performance: study on the ro-
256
botic simulator dV-Trainer. Int J Comput Assist Radiol Surg 2015 Oct 8
602. Smallwood NR, Fleshman JW, Leeds SG, Burdick JS. The use of endoluminal vacuum (E-Vac) therapy in the management of upper gastrointestinal
leaks and perforations. Surg Endosc 2015 Sep 30 [Epub ahead of print].
603. Steele SR, Varma MG, Prichard D, Bharucha AE, Vogler SA, Erdogan A,
Rao SS, Lowry AC, Lange EO, Hall GM, Bleier JI, Senagore AJ, Maykel
J, Chan SY, Paquette IM, Audett MC, Bastawrous A, Umamaheswaran
P, Fleshman JW, Caton G, OBrien BS, Nelson JM, Steiner A, Garely A,
Noor N, Desrosiers L, Kelley R, Jacobson NS. The evolution of evaluation and management of urinary or fecal incontinence and pelvic organ
prolapse. Curr Probl Surg 2015;52(2):1775; 52(3):92136.
604. Williams SB, Matin SF, Matin S, Subbarao CD. Implementation of a
very low calorie diet in patients undergoing urologic surgery: room for
improvement? Clin Genitourin Cancer 2015;13(4):e203e204.
TRANSPLANTATION (ORGAN AND PANCREATIC CELLS)
605. Asrani SK, Kamath PS. Model for end-stage liver disease score and
MELD exceptions: 15 years later. Hepatol Int 2015;9(3):346354.
606. Asrani SK, OLeary JG. Can one pill a day keep rejection away? Am J
Transplant 2015;15(5):11351136.
607. Asrani SK, OLeary JG. The changing liver transplant waitlist: an emerging liver purgatory? Gastroenterology 2015;148(3):493496.
608. Bellin MD, Gelrud A, Arreaza-Rubin G, Dunn TB, Humar A, Morgan
KA, Naziruddin B, Rastellini C, Rickels MR, Schwarzenberg SJ, Andersen DK. Total pancreatectomy with islet autotransplantation: summary
of an NIDDK workshop. Ann Surg 2015;261(1):2129.
609. Campos-Varela I, Lai JC, Verna EC, OLeary JG, Todd Stravitz R, Forman LM, Trotter JF, Brown RS, Terrault NA; Consortium to Study
Health Outcomes in HCV Liver Transplant Recipients (CRUSH-C).
Hepatitis C genotype inuences post-liver transplant outcomes. Transplantation 2015;99(4):835840.
610. Chapman WC, Klintmalm G, Hemming A, Vachharajani N, Majella
Doyle MB, DeMatteo R, Zaydfudim V, Chung H, Cavaness K, Goldstein R, Zendajas I, Melstrom LG, Nagorney D, Jarnagin W. Surgical
treatment of hepatocellular carcinoma in North America: can hepatic
resection still be justied? J Am Coll Surg 2015;220(4):628637.
611. Chinnakotla S, Klintmalm GB. Induction and maintenance of immunosuppression. In Busuttil RW, Klintmalm GB. Transplantation of the
Liver, 3rd ed. Philadelphia: Elsevier Saunders, 2015.
612. Curry MP, Forns X, Chung RT, Terrault NA, Brown R Jr, Fenkel JM,
Gordon F, OLeary J, Kuo A, Schiano T, Everson G, Schi E, Befeler
A, Gane E, Saab S, McHutchison JG, Subramanian GM, Symonds
WT, Denning J, McNair L, Arterburn S, Svarovskaia E, Moonka D,
Afdhal N. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology
2015;148(1):100107.e1.
613. Demetris AJ, Zeevi A, OLeary JG. ABO-compatible liver allograft
antibody-mediated rejection: an update. Curr Opin Organ Transplant
2015;20(3):314324.
614. Elgharably H, Shai AE, Mason DP. Expanding the donor pool: donation
after cardiac death. Thorac Surg Clin 2015;25(1):3546.
615. Engels EA, Jennings L, Kemp TJ, Chaturvedi AK, Pinto LA, Pfeier RM,
Trotter JF, Acker M, Onaca N, Klintmalm GB. Circulating TGF-1 and
VEGF and risk of cancer among liver transplant recipients. Cancer Med
2015;4(8):12521257.
616. Fernandez H, Weber J, Barnes K, Wright L, Levy M. Financial impact
of liver sharing and organ procurement organizations experience with
Share 35: implications for national broader sharing. Am J Transplant
2015 Sep 15 [EPub ahead of print].
617. Fernandez HT, Kim PT, Anthony TL, Hamman BL, Goldstein RM,
Testa G. Inferior vena cava reconstruction for leiomyosarcoma of Zone
I-III requiring complete hepatectomy and bilateral nephrectomy with
autotransplantation. J Surg Oncol 2015;112(5):481485.
618. Ghobrial RM, Klintmalm GB. Outcome predictors in liver transplantation. In Busuttil RW, Klintmalm GB. Transplantation of the Liver, 3rd ed.
Philadelphia: Elsevier Saunders, 2015.
Volume 29, Number 2
619. Hasse JM. Nutritional aspects of transplantation in adults. In Busuttil

RW, Klintmalm GB, eds. Transplantation of the Liver, 3rd ed. Philadelphia: WB Saunders, 2015:494509.
620. Hasse JM, Chinnakotla S. Solid organ transplantation. In Cresci GA,
ed. Nutrition Support for the Critically Ill: A Guide to Practice, 2nd ed.
Boca Raton, FL: CRC Press, 2015:433454.
621. International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). Design and implementation of the International
Genetics and Translational Research in Transplantation Network. Transplantation 2015;99(11):24012412.
622. Kanak MA, Takita M, Shahbazov R, Lawrence MC, Chung WY, Dennison AR, Levy MF, Naziruddin B. Evaluation of microRNA375 as a
novel biomarker for graft damage in clinical islet transplantation. Transplantation 2015;99(8):15681573.
623. Kappel DF, Chapman WC, Conrad S, Reed A, Linderer R, Dunn S,
Niles P, Levy MF, Cawiezell T. Organ procurement organization liver
acquisition costs could more than double with proposed redistricts. Am
J Transplant 2015;15(8):22692270.
624. Kim PT, Marquez M, Jung J, Cavallucci D, Renner EL, Cattral M, Greig
PD, McGilvray ID, Selzner M, Ghanekar A, Grant DR. Long-term
follow-up of biliary complications after adult right-lobe living donor
liver transplantation. Clin Transplant 2015;29(5):465474.
625. Klein J, Kuperman M, Haley C, Barri Y, Chandrakantan A, Fischbach B,
Melton L, Rice K, Saim M, Yango A, Klintmalm G, Rajagopal A. Late
presentation of adenovirus-induced hemorrhagic cystitis and ureteral
obstruction in a kidney-pancreas transplant recipient. Proc (Bayl Univ
Med Cent) 2015;28(4):488491.
626. Klintmalm GB. Antibody-mediated rejection: immunology phenomenon
looking for a clinical phenotype. Liver Transpl 2015;21(Suppl 1):S24.
627. Klintmalm GB, Busuttil RW. The recipient hepatectomy and grafting.
In Busuttil RW, Klintmalm GB. Transplantation of the Liver, 3rd ed.
628. Lawrence MC, Borenstein-Auerbach N, McGlynn K, Kunnathodi F,
Shahbazov R, Syed I, Kanak M, Takita M, Levy MF, Naziruddin B.
NFAT targets signaling molecules to gene promoters in pancreatic -cells.
Mol Endocrinol 2015;29(2):274288.
629. Levy MF, Cowling T, Klintmalm GB. Long-term functional recovery
and quality of life: childhood, adulthood, employment, pregnancy, and
family planning. In Busuttil RW, Klintmalm GB. Transplantation of the
Liver, 3rd ed. Philadelphia: Elsevier Saunders, 2015.
630. Lima B, Chamogeorgakis T, MacHannaford JC, Gonzalez-Stawinski GV.
Hypothermic circulatory arrest in cardiac transplantation. Transplant Proc
2015;47(9):27192721.
631. Lloyd A, Klintmalm G, Qin H, Menter A. Skin cancer evaluation in
transplant patients: a physician opinion survey with recommendations.
Clin Transplant 2015;29(2):110117.
632. McKenna GJ. Making the extraordinary, ordinary: renoportal bypass
for complete portal vein thrombosis. Liver Transpl 2015;21(3):275276.
633. Mehrotra S, Kilambi V, Gilroy R, Ladner DP, Klintmalm GB, Kaplan
B. Modeling the allocation system: principles for robust design before
restructuring. Transplantation 2015;99(2):278281.
634. Mehrotra S, Kilambi V, Gilroy R, Ladner DP, Klintmalm GB, Kaplan B.
The authors reply. Transplantation 2015;99(9):e160e161.
635. OLeary JG. Donor-specic alloantibodies in liver transplantation: how should
we dene and improve long-term success? Transpl Int 2015;28(12):13591361.
636. OLeary JG, Kaneku H, Banuelos N, Jennings LW, Klintmalm GB,
Terasaki PI. Impact of IgG3 subclass and C1q-xing donor-specic HLA
alloantibodies on rejection and survival in liver transplantation. Am J
Transplant 2015;15(4):10031013.
637. OLeary JG, Orlo SL, Levitsky J, Martin P, Foley DP. Keeping high
model for end-stage liver disease score liver transplantation candidates
alive. Liver Transpl 2015;21(11):14281437.
638. Rahimi RS, OLeary JG. Post-liver transplant hepatitis C therapy. Curr
Treat Options Gastroenterol 2015;13(2):249258.
639. Rahimi RS, OLeary JG. Transfusing common sense instead of blood
products into coagulation testing in patients with cirrhosis: overtreatment safety. Hepatology 2015 Oct 16 [Epub ahead of print].
April 2016
640. Rahimi RS, Trotter JF. Liver transplantation for hepatocellular carcinoma: outcomes and treatment options for recurrence. Ann Gastroenterol
2015;28(3):323330.
641. Randell HB, Klintmalm GB. Postoperative intensive care unit management: adult liver transplant recipients. In Busuttil RW, Klintmalm GB.
Transplantation of the Liver, 3rd ed. Philadelphia: Elsevier Saunders, 2015.
642. Reddy KR, OLeary JG, Kamath PS, Fallon MB, Biggins SW, Wong F,
Patton HM, Garcia-Tsao G, Subramanian RM, Thacker LR, Bajaj JS;
North American Consortium for the Study of End-Stage Liver Disease.
High risk of delisting or death in liver transplant candidates following
infections: Results from the North American Consortium for the Study
of End-Stage Liver Disease. Liver Transpl 2015;21(7):881888.
643. Reed A, Chapman WC, Knechtle S, Chavin K, Gilroy R, Klintmalm
GB. Equalizing MELD scores over broad geographies is not the most
ecacious way to allocate a scarce resource in a value-based environment.
Ann Surg 2015;262(2):220223.
644. Reinhold SM, Lima B, Khalid A, Gonzalez-Stawinski GV, Stoler RC,
Hall SA, Chamogeorgakis T. Heart transplantation in the Ehlers-Danlos
syndrome. Proc (Bayl Univ Med Cent) 2015;28(4):492493.
645. Sanchez EQ, Klintmalm GB. Combined liver-kidney transplantation.
In Busuttil RW, Klintmalm GB. Transplantation of the Liver, 3rd ed.
646. Sanchez EQ, Klintmalm GB. Postoperative management beyond the intensive care unit: adults. In Busuttil RW, Klintmalm GB. Transplantation
of the Liver, 3rd ed. Philadelphia: Elsevier Saunders, 2015.
647. Serrano PE, Cleary SP, Dhani N, Kim PT, Greig PD, Leung K, Moulton
CA, Gallinger S, Wei AC. Improved long-term outcomes after resection
of pancreatic adenocarcinoma: a comparison between two time periods.
Ann Surg Oncol 2015;22(4):11601167.
648. Shahbazov R, Kanak MA, Takita M, Kunnathodi F, Khan O, Borenstein
N, Lawrence MC, Levy MF, Naziruddin B. Essential phospholipids
prevent islet damage induced by proinammatory cytokines and hypoxic
conditions. Diabetes Metab Res Rev 2015 Sep 17 [Epub ahead of print].
649. Singh N, Sifri CD, Silveira FP, Miller R, Gregg KS, Huprikar S, Lease
ED, Zimmer A, Dummer JS, Spak CW, Koval C, Banach DB, Shro M,
Le J, Ostrander D, Avery R, Eid A, Razonable RR, Montero J, Blumberg
E, Alynbiawi A, Morris MI, Randall HB, Alangaden G, Tessier J, Wagener MM, Sun HY. Cryptococcosis in patients with cirrhosis of the liver
and posttransplant outcomes. Transplantation 2015;99(10):21322141.
650. SoRelle JA, Kanak MA, Itoh T, Horton JM, Naziruddin B, Kane RR.
Comparison of surface modication chemistries in mouse, porcine, and
human islets. J Biomed Mater Res A 2015;103(3):869877.
651. Stone MJ, Fuller JM, Klintmalm GB. Transplantation for Budd-Chiari
syndrome. In Busuttil RW, Klintmalm GB. Transplantation of the Liver,
3rd ed. Philadelphia: Elsevier Saunders, 2015.
652. Takita M, Lara LF, Naziruddin B, Shahbazov R, Lawrence MC, Kim
PT, Onaca N, Burdick JS, Levy MF. Eect of the duration of chronic
pancreatitis on pancreas islet yield and metabolic outcome following
islet autotransplantation. J Gastrointest Surg 2015;19(7):12361246.
653. Trotter JF, Levy G. Sotrastaurin in liver transplantation: has it had a fair
trial? Am J Transplant 2015;15(5):11371138.
654. Verna EC, OLeary JG. Hepatitis C treatment in patients on the liver
transplant waiting list. Curr Opin Organ Transplant 2015;20(3):242250.
655. Verna EC, Saxena V, Burton JR Jr, OLeary JG, Dodge JL, Stravitz RT,
Levitsky J, Trotter JF, Everson GT, Brown RS Jr, Terrault NA; CRUSH-C
Consortium. Telaprevir- and boceprevir-based triple therapy for hepatitis
C in liver transplant recipients with advanced recurrent disease: a multicenter study. Transplantation 2015;99(8):16441651.
656. Woods T, Jennings NB, Fernandez HT, Onaca N, Carlile BK, Levy MF,
Gould DL, Ruiz R. Renal autotransplantation in Lynch syndrome: a viable option in a patient with contralateral metachronous ureteral cancer.
Am J Transplant 2015;15(9):25072510.
TRAUMA/PHYSICAL MEDICINE AND REHABILITATION/EMERGENCY MEDICINE
657. Cleveland S, Driver S, Swank C, Macklin S. Classifying physical activity
research following stroke using the behavioral epidemiologic framework.
Top Stroke Rehabil 2015;22(4):289298.
257
658. Cochran G, Field C, Foreman M, Ylioja T, Brown CV. Eects of brief

intervention on subgroups of injured patients who drink at risk levels.
Inj Prev 2015 Jun 29 [Epub ahead of print].
659. Dodd Z, Driver S, Warren AM, Riggs S, Clark M. Eects of adult
romantic attachment and social support on resilience and depression
in individuals with spinal cord injuries. Top Spinal Cord Inj Rehabil
2015;21(2):156165.
660. Driver S, Rachal L, Swank C, Dubiel R. Objective assessment of activity
in inpatients with traumatic brain injury: initial ndings. Brain Impairment 2015. Available at http://dx.doi.org/10.1017/BrImp.2015.20
661. Driver SJ, Warren AM, Agatrap S, Reynolds M, Trost Z, Monden
K, Hamilton R. Identifying predictors of resilience at inpatient and
three months post spinal cord injury. J Spinal Cord Med 2015. DOI:
10.1179/2045772314Y.0000000270
662. Ewing M, Funk GA, Warren AM, Rapier N, Reynolds M, Bennett M,
Mastropieri C, Foreman ML. Improving National Trauma Data Bank
coding data reliability for traumatic injury using a prospective systems
approach. Health Informatics J 2015 Oct 29 [Epub ahead of print].
663. Fann JR, Bombardier CH, Richards JS, Wilson CS, Heinemann AW,
Warren AM, Brooks L, McCullumsmith CB, Temkin NR, Warms C, Tate
DG; PRISMS Investigators. Venlafaxine extended-release for depression
following spinal cord injury: a randomized clinical trial. JAMA Psychiatry
2015;72(3):247258.
664. Fox N, Schwartz D, Salazar JH, Haut ER, Dahm P, Black JH, Brakenridge SC, Como JJ, Hendershot K, King DR, Maung AA, Moorman ML, Nagy K, Petrey LB, Tesoriero R, Scalea TM, Fabian TC.
Evaluation and management of blunt traumatic aortic injury: a practice
management guideline from the Eastern Association for the Surgery of
Trauma. J Trauma Nurs 2015;22(2):99110; J Trauma Acute Care Surg
2015;78(1):136146.
665. Fromm NM, Salisbury DB, Driver SJ, Dahdah MN, Monden KR. Functional recovery from neuroinvasive West Nile virus: a tale of two courses.
Rehabil Psychol 2015;60(4):383390.
666. Hamm J, Driver S. Strategies to increase physical activity participation
of young adults with Asperger syndrome in the community. Strategies
2015;28(3):38.
667. Klakeel M, Thompson J, Srinivasan R, McDonald F. Anterior spinal cord syndrome of unknown etiology. Proc (Bayl Univ Med Cent)
2015;28(1):8587.
668. Le D, Sha S, Gwirtz P, Bennett M, Reeves R, Callender L, Dunklin C, Cleveland S. Eect of obesity on motor functional outcome of
rehabilitating traumatic brain injury patients. Am J Phys Med Rehabil
2015;94(8):627632.
669. Petrey LB, Weddle RJ, Richardson B, Gilder R, Reynolds M, Bennett M,
Cook A, Foreman M, Warren AM. Trauma patient readmissions: why do
they come back for more? J Trauma Acute Care Surg 2015;79(5):717724.
670. Roden-Foreman JW, Warren AM, Reynolds M, Foreman ML. Recurrent hospitalization for self-injuries and suicide attempts: case study of a
super-utilizer. Proc (Bayl Univ Med Cent) 2015;28(3):331333.
671. Salisbury DB, Driver S, Parsons TD. Brain-computer interface targeting
non-motor functions after spinal cord injury: a case report. Spinal Cord
2015;53(Suppl 1):S25S26.
672. Stiers W, Barisa M, Stucky K, Pawlowski C, Van Tubbergen M, Turner
AP, Hibbard M, Caplan B. Guidelines for competency development and
measurement in rehabilitation psychology postdoctoral training. Rehabil
Psychol 2015;60(2):111122.
673. Trost Z, Agtarap S, Scott W, Driver S, Guck A, Roden-Foreman K, Reynolds M, Foreman ML, Warren AM. Perceived injustice after traumatic
258
injury: associations with pain, psychological distress, and quality of life

outcomes 12 months after injury. Rehabil Psychol 2015;60(3):213221.
674. Wang H, Robinson RD, Garrett JS, Bunch K, Huggins CA, Watson K,
Daniels J, Banks B, DEtienne JP, Zenarosa NR. Use of the SONET score
to evaluate high volume emergency department overcrowding: a prospective derivation and validation study. Emerg Med Int 2015;2015:401757.
675. Warren AM, Boals A, Elliott TR, Reynolds M, Weddle RJ, Holtz P,
Trost Z, Foreman ML. Mild traumatic brain injury increases risk for
the development of posttraumatic stress disorder. J Trauma Acute Care
Surg 2015;79(6):10621066.
EDITORIALS AND MISCELLANEOUS
676. Davis M. Directions to a lost place: a parable for modern times. Proc
677. Ellis PR III, Roberts WC. Paul Roscoe Ellis III, MD: a conversation with
the editor. Proc (Bayl Univ Med Cent) 2015;28(1):97107.
678. Frost SM, Roberts WC. Steven Marshall Frost, MD: a conversation with
the editor. Proc (Bayl Univ Med Cent) 2015;28(1):108117.
679. Gentry L. Teaching with questions. Proc (Bayl Univ Med Cent)
2015;28(1):118119.
680. Hellmann DB, Roberts WC. David Bruce Hellmann, MD: a conversation with the editor. Proc (Bayl Univ Med Cent) 2015;28(3):409419.
681. Lister ED, Ledbetter TG, Warren AM. The engaged physician. Mayo
Clin Proc 2015;90(4):425427.
682. Marcus PB. Feroze Novroji Ghadially, 19202014: a personal remembrance. Proc (Bayl Univ Med Cent) 2015;28(4):531537.
683. Miller AM, Roberts WC. Alan Marshall Miller, MD, PhD: a conversation with the editor. Proc (Bayl Univ Med Cent) 2015;28(2):237246.
684. Roberts WC. Good books in cardiovascular disease received in 2014 and
in early 2015. Am J Cardiol 2015;115:16231625.
685. Roberts WC. Proceedings of the editorial board meeting of The
American Journal of Cardiology in March 15, 2015. Am J Cardiol
2015;115:16261629.
686. Roberts WC. A week in Havana, Cuba, in February 2015. Proc (Bayl
Univ Med Cent) 2015;28(4):538540.
687. Roberts WC. Facts and ideas from anywhere. Proc (Bayl Univ Med Cent)
2015;28(1):126133.
2015;28(2):258265.
2015;28(3):421432.
2015;28(4):541552.
691. Roberts WC. Proliferation of online medical journals. Am J Cardiol
2015 Nov 11 [Epub ahead of print].
692. Stefanos S, Paul A, Thakur R, Bass K, East C. The gender of authors in
the Baylor Proceedings: a reection of both current sta composition and
lesser number of publications by female physicians. Proc (Bayl Univ Med
Cent) 2015;28(4):457460.
693. Warren B. Book review: Users Guides to the Medical Literature. Proc (Bayl
Univ Med Cent) 2015;28(2):256257.
Note: This list (nalized on February 11, 2016) was based on submissions
from medical and allied health sta and on PubMed searches. Although the
list is representative of the years publications, some articles and book chapters
were undoubtedly missed. Sta are encouraged to submit their publications
each year. For more information or to submit publications for this list, please
contact Cynthia.Orticio@BSWHealth.org.
Volume 29, Number 2
Instructions for authors
aylor University Medical Center Proceedings welcomes research articles, review articles, case studies, and editorials
from Baylor and non-Baylor authors. Manuscripts containing Baylor data are particularly desired. Send all manuscripts
and editorial correspondence to William C. Roberts, MD, Editor in
Chief, Baylor Scientic Publications Oce, 3500 Gaston Avenue, Dallas, Texas 75246; phone: 214-820-9996; fax: 214-820-4064; e-mail:
cynthiao@BaylorHealth.edu.
MANUSCRIPT SUBMISSION
Submit the word processing document by e-mail to cynthiao@
BaylorHealth.edu. Large les may be sent using YouSendIt or SendNow.
Cover letter and attachments: According to journal policies outlined below, list suggested reviewers and discuss potential conicts
of interest in your cover letter and provide as attachments copies of
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Schedule: The journal operates on a rolling schedule, but in general
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issue, March 1; and October issue, June 1. The editorial oce cannot
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In addition to multipatient studies (original research articles),
Proceedings publishes several other article types.
Case studies: Include an abstract, a single-paragraph introduction,
a case description of 0.5 to 2 double-spaced pages, and a discussion
of 1 to 5 double-spaced pages. Up to 25 references are acceptable
(although many case reports have 5 to 10). The maximum number of
gures and tables (combined) is 6.
Historical studies: Abstracts are recommended. There is no word
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Editorials: There is no word limit, but most editorials are 800
to 1600 words.
Book reviews: See past issues for format. There is no word limit,
but most book reviews are 800 to 1600 words.
Avocations: Submit an image le for your painting or photograph
or a discussion of your hobby for a maximum of 300 words.
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MANUSCRIPT PREPARATION
Format: Type manuscripts double spaced, leaving 1-inch margins.
Number all pages, including the title page. Indent paragraphs. Start the
rst paragraph of the text and the beginning of the reference section
on a new page and place gures on separate pages.
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Journal article: OShaughnessy J, Osborne C, Pippen JE, Yoe
M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib
plus chemotherapy in metastatic triple-negative breast cancer. N
Engl J Med 2011;364(3):205214.
Book chapter: Ramsay M. Liver transplantation and portopulmonary hypertension. In Milan Z, ed. Cardiovascular Diseases
and Liver Transplantation. New York: Nova Biomedical Books,
2011:8397.
Book: Gulati G, Filicko-OHara J, Krause JR. Case Studies in
Hematology and Coagulation. Chicago, IL: American Society for
Clinical Pathology Press, 2012.
Authors using Endnote can access Proceedings reference style
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ManuscriptPreparation.aspx. Personal communications and unpublished data should not be used as references; they should be
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Tables and gures: Number tables and gures in the order in which
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259
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If a manuscript was previously reviewed by another journal, authors
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Duplicate publication: When submitting the manuscript, provide a copy of any published or submitted article that is similar to
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whether the manuscript in question would be a duplicate publication.
Once manuscripts are accepted, authors transfer copyright to Baylor
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must review the nal text and be prepared to take public responsibility
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Conict of interest: Grant support for a particular study must be
indicated on the title page. In addition, authors must communicate to
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potential conicts of interest. Examples include honoraria, educational
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260
Use of protected health information: Authors should not refer

to patients by name or initials or provide other specic identifying
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Permissions: Permission is required for reproduction of any material, including gures and tables, that has been published elsewhere.
When submitting manuscripts, provide written documentation that
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photographs in which the subject can be recognized, submit release
authorizations at the time of manuscript submission.
For additional information, please contact Cynthia Orticio, managing editor, at 214-820-9996 or cynthiao@BaylorHealth.edu.
1.
2.
Chippereld L, Citroma L, Clark J, David FS, Neck R, Evangelista

M, Gonzalez J, Groves T, Magan J, Mansa B, Miller C, Mooney LA,
Murphy A, Shelton J, Wilson PD, Weigl A. Authors submission toolkit:
a practical guide to getting your research published. Cur Med Res Open
2010;26(8):19671982.
Roberts WC. Formulating an answerable question, displaying data, illustrating, writing, reviewing, and editing manuscripts for publication
in medical journals. Am J Cardiol 2012;110(2):290306.
MANUSCRIPT SUBMISSION CHECKLIST

The entire manuscript is double-spaced and in one Word le, in
the following order: title page, abstract, text, references, tables,
gures (either gure legends only or gures embedded plus
legends). Page numbers appear on the bottom of each page.
The title page has required elements: title, authors (with full
names and degrees), aliations, and address for corresponding author.
A single-paragraph abstract of 150 to 250 words is included.
For case studies: After the abstract, the manuscript includes
a single-paragraph introduction, a case discussion of 0.5 to
2 double-spaced pages, and a discussion of 0.5 to 5 doublespaced pages. The manuscript does not exceed the limit of
25 references or 6 gures and tables.
Figures are high-resolution. Photographs are 350-ppi ti or
jpeg les.
References include all authors, the full article title, the journal
abbreviation from Index Medicus, the volume and issue number,
and inclusive page numbers. References in the text appear in
parentheses, rather than in superscript or footnotes or endnotes.
All authors have approved the version to be submitted.
Manuscripts that do not meet these requirements may be returned to
authors before peer review is initiated.
Volume 29, Number 2
Volume 29
Number 2
April 2016
Scott & White Medical Center Temple
Baylor Scott & White Medical Center - Marble Falls
Baylor All Saints Medical Center at Fort Worth
Baylor Medical Center at McKinney
Baylor Scott & White Hospital - Hillcrest
Baylor Scott & White Medical Center - Round Rock

Pages 117260
www.BaylorScottandWhite.com
Review Articles
131 Review of behavioral health integration in primary care at Baylor
Scott and White Healthcare, Central Region by J. B. Jolly et al
137 Invited commentary by C. Couch
Historical Article
138 Medical and surgical care during the American Civil War, 1861
1865 by R. F. Reilly
Baylor Regional Medical Center at Grapevine
The largest not-for-prot health care system in Texas,

and one of the largest in the United States, Baylor Scott
& White Health was born from the 2013 combination of
Baylor Health Care System and Scott & White Healthcare.
For more information on our 43 hospitals and more than
500 patient care sites, please visit www.BaylorHealth.com
and www.sw.org.
Original Research
119 The characteristics of Mohs surgery performed by
preceptorships by H. K. Steinman et al
124 Virtual reality and brain computer interface in
neurorehabilitation by D. B. Salisbury et al
128 Safety and efcacy of packed red blood cell transfusions at
different doses in very low birth weight infants by L. H. Mallett et al
Case Studies
143 Exercise-induced acute compartment syndrome in a young man,
occurring after a short race by B. Basnet et al
145 Table tipping and a near-miss fall after unlocking a surgical
table holding a morbidly obese patient by R. T. Booth et al
147 Use of ultrasound guidance to remove entrapped stimulating
popliteal catheters by R. K. McAllister et al
150 Baclofen-responsive hiccups after esophageal stenting for
malignancy-related dysphagia by V. Sharma et al
151 Specicity of testing in a cardiac rehabilitation setting resulting
in a patients return to high-intensity outdoor activity following
aortic dissection repair by S. Bartee et al
154 Invited commentary: Simulated performance testing to
determine the aortic dissection patients potential for vigorous
physical activity by B. A. Franklin
157 Cardiovascular autonomic neuropathy by N. McCarty and B. Silverman
160 Cardiac arrest refractory to standard intervention in atypical
Timothy syndrome (LQT8 type 2) by L. R. Phillipp and F. H.
Rodriguez III
163 Holter monitor recordings in a man who snores by D. L. Glancy
and P. Vijitbenjaronk
165 An interesting electrocardiogram by H. H. McClure Jr.
166 Takotsubo cardiomyopathy after administration of
norepinephrine by K. Sherif et al
168 Acute myocardial infarction with isolated congenitally corrected
transposition of the great arteries by J. Zimmerman et al
171 Isolated congenitally corrected transposition of the great arteries
with dextroversion discovered incidentally in a patient with
cocaine-induced acute myocardial infarction by A. Tandon et al
174 Invited commentary: The specialty of adult congenital heart
disease by A. Cedars
176 Surgical considerations for the explantation of the Parachute

left ventricular partitioning device and the implantation of the
HeartMate II left ventricular assist device by Y. Ravi et al
178 Intracranial aneurysm and sildenal by A. Adiga et al
181 Infective endocarditis caused by Klebsiella oxytoca in an
intravenous drug user with cancer by A. Mohamed et al
183 Rapidly enlarging neck mass in a neonate causing airway
compromise by K. Schmidt et al
185 Serendipitous discovery of peritoneal mesothelioma by A. Jaster
and J. Wachsmann
188 Pneumomediastinum, pneumorrhachis, and subcutaneous emphysema
in Pneumocystis jiroveci pneumonia in AIDS by N. Saleem et al
191 Multiple dural-based hemangiopericytomas by E. Stroberg et al
194 Colorectal cancer implant in an external hemorrhoidal skin
tag by L. Liasis and H. T. Papaconstantinou
196 Bilateral synchronous plasmacytoma of the testis by G. Narayanan et al
198 Presentation of epidermolytic acanthomas as multiple tan
papules on the vulva by J. W. Fletcher et al
200 Rumpel-Leede phenomenon presenting as a hypertensive
urgency by D. Varela et al
202 Arm pain and erythema by B. M. Barth and A. L. Juergens
204 Rheumatoid meningitis associated with iniximab by S. Seago et al
207 Cryptococcal meningitis in a patient with sarcoidosis by T. N.
Adams and M. Gibson
209 Thyroid hormone resistance and its management by A. M. Rivas et al
212 The price of a 15-year delay in diagnosis of Sheehans
syndrome by R. Parikh et al
214 Linezolid-induced serotonin toxicity in a patient not taking monoamine
oxidase inhibitors or serotonin receptor antagonists by J. Sutton et al
Editorial and Book Review
220 On John Keats and Blue Zones by J. D. Cantwell
224 Book review: In Vitro Fertilization Comes to America by S. P. Marynick
From the Editor
230 Facts and ideas from anywhere by W. C. Roberts
Miscellany
118 Clinical research studies enrolling patients
164 In memoriam
187 Avocations: Photograph by R. Solis
216 Baylor news
226 Reader comments: Hearts considered for transplantation and
takotsubo syndrome by J. E. Madias, S. Y-Hassan, author reply
by Y. Ravi; Electronic medical records by L. Hughes; Facts and
ideas by T. Gore, J. Woods; Cuba by S. P. Marynick
238 2015 publications of the Baylor Scott & White Health North
Division medical and scientic staff
259 Instructions for authors
www.BaylorHealth.edu/Proceedings
Indexed in PubMed, with full text available through PubMed Central

April 2016 BUMC Proceedings - Blue Zones - Pag 220

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Volume 29

The peer-reviewed journal of Baylor Scott & White Health

Scott & White Medical Center Temple

Baylor Scott & White Medical Center - Marble Falls

Baylor All Saints Medical Center at Fort Worth

Baylor Medical Center at McKinney

Baylor Scott & White Hospital - Hillcrest

Baylor Scott & White Medical Center - Round Rock

Baylor University Medical Center Proceedings

Baylor University Medical Center at Dallas

Volume 29, Number 2 April 2016

Baylor Regional Medical Center at Grapevine

The largest not-for-prot health care system in Texas,

176 Surgical considerations for the explantation of the Parachute

Baylor University Medical Center

Design and Production

Subscriptions are oered free to libraries, physicians aliated with Baylor,

Clinical research studies enrolling patients through

Contact information (name, phone number, and e-mail address)

Chronic obstructive pulmonary disease, asthma (adult)

Jana Holloway, RRT, CRC

Breast, ovarian, endometrial, prostate, brain, lung, bladder, colorectal,

Type 1 and type 2 diabetes, cardiovascular events

Type 2; cardiac events

Diabetes (Fort Worth)

Heart and vascular

Inflammatory bowel disease

Dr. Themistocles Dassopoulos

Aortic aneurysms, coronary artery disease, hypertension, poor leg

Heart and lung transplant, mechanical assist device such as LVAD

Elizabeth Owens, BA, CCRP

Heart and vascular disease

Atrial fibrillation, atrial fibrillation post PCI

Heart and vascular disease

At risk for heart attack/stroke; previous heart attack/stroke/PAD; cholesterol

Heart and vascular

Aortic aneurysm; coronary artery disease; renal stent for uncontrolled

Bryan King, LVN

Type 2 diabetes with chronic kidney disease

Quynh Lan Doan

Multiple sclerosis, stroke

Interventional stroke therapy

Rheumatoid arthritis, psoriatic arthritis, lupus, gout,

Bone marrow, blood stem cells

Proc (Bayl Univ Med Cent) 2016;29(2):118

The characteristics of Mohs surgery performed by

Proc (Bayl Univ Med Cent) 2016;29(2):119123

in residency, postresidency courses followed by observational

Dermatology group (11%)

Multispecialty group (11%)

Solo practice (67%)

Career case experience

*CP indicates course followed by preceptorship; C, Course; R, Residency.

a porcine xenograft. A total of 72 cases (3.9%) were referred to

Baylor University Medical Center Proceedings

Volume 29, Number 2

Table 2. Tumors treated with Mohs surgery: study data versus

Table 4. Number of Mohs surgery stages to obtain clear margins:

Number of Mohs surgery stages

First author, year (ref)

7.6% 2.7% 0.9%

Cook, 1998 (20)

4.0% 3.5% 3.0%