637 PDF

Clifford D.
Packer
Gabrielle N. Berger
Somnath Mookherjee
Writing Case Reports

A Practical Guide
from Conception
through Publication
123
Clifford D. Packer
Gabrielle N. Berger
Somnath Mookherjee

A Practical Guide from Conception
through Publication
Clifford D. Packer, MD Somnath Mookherjee, MD
Case Western Reserve University Division of General Internal
School of Medicine Medicine
Cleveland, Ohio Department of Medicine
USA University of Washington
School of Medicine
Gabrielle N. Berger, MD Seattle, Washington
Division of General Internal USA
Medicine
Department of Medicine
University of Washington
School of Medicine
Seattle, Washington
USA
ISBN 978-3-319-41898-8 ISBN 978-3-319-41899-5 (eBook)

DOI 10.1007/978-3-319-41899-5
Library of Congress Control Number: 2016955956
Springer International Publishing Switzerland 2017

This work is subject to copyright. All rights are reserved by the Publisher,
whether the whole or part of the material is concerned, specifically the rights of
translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduc-
tion on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or
dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service
marks, etc. in this publication does not imply, even in the absence of a specific
statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and
information in this book are believed to be true and accurate at the date of pub-
lication. Neither the publisher nor the authors or the editors give a warranty,
express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made.
Printed on acid-free paper
This Springer imprint is published by Springer Nature

The registered company is Springer International Publishing AG Switzerland
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
CDP dedicates this book to his wife, Marie
Sullivan.
CDP acknowledges his medical students,

colleagues, and patients at the Louis Stokes
Cleveland VA Medical Center, all of whom helped
to make this book possible.
GB dedicates this book to all the students and

residents who inspire her to just write it up!
GB wishes to thank her colleagues at the University

of Washington School of Medicine and the
University of Washington Medical Center for their
camaraderie and support.
SM dedicates this book to his best friend,

Leah Smith.
SM wishes to acknowledge the University of

Washington School of Medicine, Department
of Medicine, and Division of General Internal
Medicine for supporting this work.
Preface
Why write a book about writing case reports? One very prac-
tical reason is to bridge the gap between aspiration (we
ought to write this up) and publication. Despite the increas-
ing numbers of case reports published each year, we suspect
that this gap remains wide, especially for medical trainees and
physicians practicing in the community. Consequently, inter-
esting and potentially important cases that ought to be in
circulation are going unpublished. Second, although there are
many fine articles on how to write case reports, and one
excellent book Milos Jeniceks Clinical Case Reporting in
Evidence-Based Medicine we think that prospective case
report authors need a practical, single-source guide to the
whole process, from case selection through publication. In the
twenty-first century, this guide must go beyond the tradi-
tional case report to instruct potential authors on its many
modern variants: clinical vignette abstracts, case series, clini-
cal images, clinical quizzes, adverse drug reaction case reports,
n-of-1 trials, and clinical problem-solving cases. Todays case
report author needs to be versatile; that classic case of Mirizzi
syndrome may not work as a straight case report, but it could
be a superb clinical image or clinical reasoning case. Our aim
is to help authors navigate these many options, select the
form and venue that works best for their case, and then write
it up in a concise, informative, and publishable style.
But perhaps the best reason for writing this book is sim-
ply that case reports are fun to write, fun to read, great for
teaching, and useful in our clinical practices. I am extremely
lucky to have found two co-authors, Gabrielle N. Berger and
vii
viii Preface
Somnath Mookherjee, who not only feel the same way about
case reports but have been willing to devote considerable
time and energy to writing about them.
Over the course of our collaboration, what started out as a
simple case reporting handbook has evolved into something
more a handbook with supplemental essays on the history,
educational value, career enhancements, scholarly opportuni-
ties, social media aspects, and future prospects of the case
report. A major goal of any case report is to put the case in
context; our parallel goal is to put the art and science of case
reporting in context for our readers. Case report authors
should understand that they are part of a great historical tra-
dition, that case reports can be powerful educational tools,
and that writing case reports can lead to exciting scholarly
opportunities, new collaborations, and useful clinical insights.
Writing case reports, in other words, can help to make us bet-
ter teachers and physicians.
If even a few medical students, residents, and practicing
physicians publish their first case reports with the help of this
book, it will have served its purpose.
Cleveland, OH, USA Clifford D. Packer, MD

May 8, 2016
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Clifford D. Packer
2 The Historical Tradition of Case Reporting . . . . . . . 9

Clifford D. Packer
3 The Educational Value of Case Reports . . . . . . . . . . 23

Clifford D. Packer
4 Practical Benefits of Case Reporting . . . . . . . . . . . . . 33

Gabrielle N. Berger
5 Is My Case Good Enough? . . . . . . . . . . . . . . . . . . . . 43

Somnath Mookherjee and Gabrielle N. Berger
6 How to Get Started . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

7 How to Write a Traditional Case Report. . . . . . . . . . 65

Clifford D. Packer
8 Special Considerations . . . . . . . . . . . . . . . . . . . . . . . . . 97
Clifford D. Packer
9 How to Write a Clinical Vignette Abstract . . . . . . . . 121

Jeffrey Wiese and Somnath Mookherjee
ix
x Contents
10 How to Write a Clinical Problem

Solving Manuscript . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Gurpreet Dhaliwal and Gabrielle N. Berger
11 Submitting a Case Report Manuscript . . . . . . . . . . . . 151

Gabrielle N. Berger and Somnath Mookherjee
12 The View from the Journal . . . . . . . . . . . . . . . . . . . . . 157

Somnath Mookherjee and Brian J. Harte
13 Its Published! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

Clifford D. Packer
14 The Future of the Case Report . . . . . . . . . . . . . . . . . . 185

Clifford D. Packer
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Contributors
Gabrielle N. Berger, MD Division of General Internal

Medicine, Department of Medicine, University of Washington
School of Medicine, Seattle, WA, USA
Gurpreet Dhaliwal, MD Department of Medicine, University

of California San Francisco, San Francisco, CA, USA
Brian J. Harte, MD Department of Medicine, Cleveland

Clinic Lerner College of Medicine at Case Western Reserve
University, Cleveland, OH, USA
Somnath Mookherjee, MD Division of General Internal

Medicine, Department of Medicine, University of Washington
School of Medicine, Seattle, WA, USA
Clifford D. Packer, MD Case Western Reserve University

School of Medicine, Cleveland, OH, USA
Jeffrey Wiese, MD Department of Internal Medicine, Tulane

University School of Medicine, New Orleans, LA, USA
xi
Chapter 1
Introduction
Clifford D. Packer
There are many good reasons to write case reports: to edu-

cate other trainees and physicians; to contribute evidence
that could be useful to others for patient care; to learn (and
teach) scholarly writing skills; to be the first to describe a new
syndrome or a serious adverse drug reaction; to analyze clini-
cal reasoning and decision-making; to propose new hypothe-
ses on mechanisms of disease; to participate in innovative
research in personalized medicine; to gain academic recogni-
tion and career advancement; and to take part in the histori-
cal tradition of case reporting that goes back almost 4000
years.
This book has two purposes. First, it can be used as a com-
prehensive handbook or guide for anyone interested in writ-
ing a medical case report. Chapters 5, 6, 7, 8, 9, 10, 11, and 12
cover every practical step from conception and case selection
(Is my case good enough?) to obtaining consent, collecting
images and other data, assembling a team of authors, defining
a target audience, selecting a journal, and responding to peer
review. Chapters 7, 8, 9, and 10 give detailed, step-by-step
instructions on how to write traditional case reports, adverse
drug reaction case reports, case series, n-of-1 case studies,
clinical image or clinical quiz articles, clinical vignettes, and
Springer International Publishing Switzerland 2017 1

C.D. Packer et al., Writing Case Reports,
DOI 10.1007/978-3-319-41899-5_1
2 Chapter 1. Introduction
clinical problem-solving cases. These chapters have numerous

figures, tables, images, and excerpts of published case reports
(including many written by the authors) to illustrate and rein-
force the strategies that lead to publication.
The second purpose of this book is to give the interested
reader some perspective on the historical, educational,
social, and cultural aspects of case reporting. Chapter 2
traces the history of case reporting from ancient Egypt to
the present day, focusing on the effects of culture and tech-
nology on the evolving form and structure of the case
report. Chapter 3 discusses the educational benefits of
reading and writing case reports, both for trainees and
experienced physicians. Chapter 4 covers the practical
benefits of case reporting, including contributing to the
medical literature, career development, and better patient
care. Chapter 13 explores postpublication issues: press
releases and media exposure, peer review and editorial
writing opportunities, indexing, citations, and use of social
media to track article views and comments. Finally, Chap.
14 speculates on the uncertain future of the case report.
We hope that readers who want to write case reports will
go beyond the handbook and take the time to learn
more about this ancient yet still vibrant form of medical
communication.
The Violinist Who Lost His Vibrato

Case reports can arise in unexpected places. One of my
first published case reports began with a conversation I
had with a violinist at a chamber music party. On hearing
that I was a physician, he began complaining to me about
the side effects of one of his blood pressure medicines.
Normally, this would elicit a polite nod or two, followed by
a quick move to the opposite side of the room. However,
something about his story intrigued me. When he was pre-
scribed daily atenolol for hypertension, he began to have
difficulty with initiating and controlling his vibrato, which
The Violinist Who Lost His Vibrato 3
is produced by quick oscillations of the violinists hand to

create a pleasantly pulsating tone. The problem worsened,
and finally came to a head when he began rehearsing the
famous solo in Massenets Meditation from Thais, a slow
piece that requires varied and dramatic vibrato effects.
Despite hours of practice, the vibrato was too slow, too
wide, and difficult to control. In desperation, he turned
to a physician with experience in music medicine, who
weaned him off the atenolol and started him on an
angiotensin-converting enzyme inhibitor for hypertension.
His vibrato quickly recovered, and his subsequent perfor-
mance of the Meditation was completely successful. This
conversation led eventually to a case report and review of
the literature on beta-blockers, stage fright, and the para-
doxical effects of atenolol on the controlled tremor of
vibrato [1].
Another case report was born when a patient with unex-
plained hypokalemia rolled into my office with a 2 l bottle of
cola in the front basket of his electric scooter. His potassium
had been low and almost impossible to replete for 2 years; an
extensive work-up had revealed nothing. As I looked at him,
I suddenly realized that the big cola bottle was the
MacGuffin in the case. When I asked him about it, he
admitted to drinking 4 l per day. This led to a diagnosis of
cola-induced hypokalemia, which was confirmed when his
potassium normalized after he reduced his cola intake [2].
What did these two cases have in common? An unex-
pected association, a mystery solved, but also the excite-
ment of discovery. Vladimir Nabokov, in his Lectures on
Literature, wrote that a wise reader reads the book of
genius not with his heart, not so much with his brain, but
with his spine.[3] In a very similar way, experienced phy-
sicians detect reportable cases with their spines, by the
telltale tingle they feel when confronted with true nov-
elty. The purpose of this book is to help physicians and
students to sustain and preserve that initial frisson of
excitement by learning to write up their cases for
publication.
Evidence Value of Case Reports: What

Actually Happened
Case reports may remain the lowest or weakest level of

evidence with respect to causality, writes Riaz Agha, but
they remain the first line of evidence of what actually hap-
pened [4]. Case reports derive their value as evidence from
the real-world authenticity of the cases they describe. As
Milos Jenicek reminds us, Everything begins with the per-
sonal experience of the physician and his patient, at the office
or hospital [5]. Randomized trials deal with populations of
patients, under carefully controlled conditions; case reports
deal with individual patients in the randomness of everyday
life. Randomized trials are mainly confirmatory; they bring
a final quantification of the evidence, Jan Vandenbroucke
notes, but offer little scientific novelty in themselves [6].
Case reports are all about novelty, serendipity, new ideas,
fresh hypotheses, and therapeutic surprises. Rather than pro-
viding confirmation, they provide inspiration. Case reports
and case series supply most of the ideas and hypotheses that
are tested and confirmed in randomized trials. Case reports
are the lone prospectors who pan for gold and chip away at
rocks with their hammers; randomized trials are the orga-
nized mining operations that rush in with their feeders and
crushers and leaching tanks when the prospector finds a
promising nugget.
Case reports are traditionally regarded as the base of the
evidence pyramid, with randomized controlled trials at the
top (see Fig. 4.1). Evidence-based medicine tells us to use
these high-quality randomized trials to guide our decision-
making. This is all very well when patients present with text-
book illnesses, and do not have multiple comorbid conditions.
However, if your practice involves patients with complex
medical histories who present with confusing and atypical
symptoms, you will soon discover that randomized trials do
not have all the answers. Fortunately, there are more than 1.7
million case reports indexed in PubMed, and a literature
Impact of Case Reports 5
search will usually yield a handful of similar cases that may

give some guidance on diagnosis and management. Thus, we
turn the evidence pyramid on its head when randomized tri-
als are lacking, and case reports and case series what actu-
ally happened become the best available evidence.
Impact of Case Reports

Those who consider writing case reports a quaint, outmoded,
and marginal pursuit should consider the dramatic and con-
tinuing impact of case reports in the twenty-first century.
Whereas randomized trials often take years to plan and exe-
cute, case reports can function as reports from the frontline
with rapid publication and wide dissemination of critical
information on the natural history, prognosis, and treatment
of emerging diseases. For example, a recent case report, Zika
Virus Associated with Microcephaly [7], describes the
autopsy findings of the 29-week fetus of a woman with symp-
toms of Zika virus infection. The autopsy revealed micro-
cephaly, almost complete agyria, hydrocephalus, and other
major brain abnormalities. Zika virus was found in the fetal
brain tissue on reverse transcriptasepolymerase chain reac-
tion (RT-PCR) assay, and the complete Zika virus genome
was recovered from the fetal brain. This report provided the
best evidence to date that Zika virus infection in pregnant
women causes fetal microcephaly. Case reports played a simi-
lar frontline role in the recent Ebola virus epidemic in Africa,
with critical information on natural history, virology, common
complications (including Gram-negative septicemia and
encephalopathy), and optimal ICU treatment for survival [8].
Similarly, case reports and case series have made critical con-
tributions in outbreaks of SARS [9], MERS [10], AIDS [11],
toxic shock syndrome [12], West Nile Virus [13], and many
others.
In addition to recognition and description of new diseases,
case reports continue to play important roles in pharmacovigi-
lance (see Chap. 8), hypothesis-generation and study of
mechanisms of disease (Chap. 7), medical education (Chaps. 3, 8,

9, and 10), researching rare disorders and outliers (Chap. 8),
personalized medicine (Chap. 8), study of the history of medi-
cine (Chap. 2), quality assurance, and solving ethical dilemmas
[6, 14, 15].
Case Reports: Form and Function

in the Twenty First Century
Over the centuries, case reports have evolved to fit the socio-
cultural and technological contexts of their times. The twenty-
first century has seen an expanding variety of roles for case
reports (Fig. 1.1), probably arising from the rapid growth in
computer technology, with increasingly powerful applications
in research, education, imaging, and bioinformatics.
For example, the study of individual outlier cancer survi-
vors has become one of the hottest areas in cancer research
with the advent of rapid and inexpensive genomic sequenc-
ing; we can now sequence hundreds of these individuals to
find the ones with mutations that predict response to a
Traditional case report

Adverse drug reaction
Exceptional responder case report
trial
N-of-1 trial Pharmacogenomic

case study
Study of disease Case series
Educational case
mechanisms report
Quality assurance
case series
Clinical image
Clinical vignette
Cohort study
Clinical quiz
Clinical problem-solving case
Clinical reasoning case
Figure 1.1 Taxonomy of the twenty first century case report

References 7
specific treatment. Similarly, n-of-1 trials of patients with

chronic conditions such as hypertension, sleep apnea, and
Parkinsons disease have benefitted from the development of
advanced phenotypic monitoring devices to assess treat-
ment response. In medical education, the traditional case
report has morphed into a variety of forms, including clinical
images, videos, quizzes, poster vignettes, and clinical problem-
solving cases, all widely available via electronic media. Case
series can now be electronically combined and analyzed for
purposes of outcome studies, case definition, quality assur-
ance, and multi-institutional registries.
Clearly, we have come a long way from the traditional
print journal case reports of 30 years ago. In fact, it can be
argued that case reports have changed more in form and
function over the past 30 years than in the 2000 years between
Hippocrates Epidemics and the first modern case reports.
How long can case reports continue to grow and reshape
themselves and reach ever-increasing numbers of readers?
Will the traditional case report stay relevant, or will it wither
away and become a forgotten relic in 30 years? We hope that
readers of this book especially medical students, residents,
and early-career physicians will take these questions to
heart and preserve the best that case reports have to offer.
References
1. Packer CD, Packer DM. Beta-blockers, stage fright, and vibrato:
a case report. Med Probl Perform Art. 2005;20(3):12630.
2. Packer CD. Chronic hypokalemia due to excessive cola con-
sumption: a case report. Cases J. 2008;1:32.
3. Nabokov V. Lectures on literature. New York: Harcourt Brace
Jovanovich; 1982. p. 6.
4. Agha R. Time for a new approach to case reports. Int J Surg
Case Rep. 2010;1(1):13.
5. Jenicek M. Clinical case reporting in evidence-based medicine.
Oxford: Butterworth-Heinemann; 1999. p. 5.
6. Vandenbroucke JP. Case reports in an evidence-based world. J R
Soc Med. 1999;92(4):15963.
7. Mlakar J, Korva M, Tul N, Popovi M, Poljak-Prijatelj M, Mraz

J, et al. Zika virus associated with microcephaly. N Engl J Med.
2016;374:9518.
8. Kreuels B, Wichmann D, Emmerich P, Schmidt-Chanasit J, de
Heer G, Kluge S, et al. A case of severe Ebola virus infection
complicated by gram-negative septicemia. N Engl J Med.
2014;371:2394401.
9. Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M,
et al. A cluster of cases of Severe Acute Respiratory Syndrome
in Hong Kong. N Engl J Med. 2003;348:197785.
10. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME,
Fouchier RAM. Isolation of a novel coronavirus from a man
with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:
181420.
11. Hymes KB, Greene JB, Marcus A, William DC, Cheung T, Prose
NS, et al. Kaposis sarcoma in homosexual men a report of
eight cases. Lancet. 1981;2(8247):598600.
12. Todd J, Fishaut M, Kapral F. Toxic-shock syndrome associated
with phage-group-I Staphylococci. Lancet. 1978;2(8100):11168.
13. Asnis DS, Conetta R, Texeira AA, Waldman G, Sampson
BA. The West Nile Virus outbreak of 1999 in New York: the
Flushing Hospital experience. Clin Infect Dis. 2000;30(3):4138.
14. Vandenbroucke JP. In defense of case reports and case series.
Ann Intern Med. 2001;134:3304.
15. Nissen T, Wynn R. The clinical case report: a review of its merits
and limitations. BMC Res Notes. 2014;7:264.
Chapter 2
The Historical Tradition
of Case Reporting
Clifford D. Packer
The Case Report in Ancient

and Medieval Times
The medical case report as we know it today is not a static

form of medical communication. It has evolved over almost
4000 years, and the format, content, and uses of case reports
have undergone remarkable changes according to the shift-
ing historical, technological, and cultural contexts. While the
tradition of case reporting is ancient, our current way of writ-
ing a case report is a relatively recent development.
The first known medical case reports, circa 1600 BC, were
written and preserved on an Egyptian papyrus. They comprise
a series of 48 cases which discuss injuries and disorders of the
head and upper torso, and include an accurate description of
a maneuver to reduce a jaw dislocation [1]. Another ancient
Egyptian medical treatise, the Ebers papyrus (1552 BC), is a
110-page scroll which contains folk remedies, magical potions,
and descriptions of a wide variety of diseases, including a dis-
order of frequent urination that is probably the first report of
diabetes mellitus (although an ancient Hindu text from the
same period noted that ants were attracted to the urine of
people with a mysterious wasting disease) [2]. Egyptian medi-
cine was practiced by physician-priests, and treatment, though
often practical and occasionally useful, was inextricably

DOI 10.1007/978-3-319-41899-5_2
10 Chapter 2. The Historical Tradition of Case Reporting
entwined with magic [3]. In contrast, the Hippocratic case

histories from the Greek classical era (ca. 400 BC) show no
belief in supernatural origins of disease, and are characterized
by objective and detailed descriptions of the findings and
courses of various illnesses [1]. The physician-narrator was
generally an observer, and did not intervene or otherwise par-
ticipate in the case [4]. This case history from the Epidemics,
of a patient with what sounds like a foot infection complicated
by cellulitis and overwhelming sepsis, is typical:
Criton, in Thasus, while still on foot, and going about, was seized
with a violent pain in the great toe; he took to bed the same day,
had rigors and nausea, recovered his heat slightly, at night was
delirious. On the second, swelling of the whole foot, and about the
ankle erythema, with distention, and small bullae (phlyctaenae);
acute fever; he became furiously deranged; alvine discharges bil-
ious, unmixed, and rather frequent. He died on the second day
from the commencement. [5]
Hippocrates crowning achievement was the Aphorisms, a

collection of 412 short, pithy maxims which conveyed the col-
lected teaching points of his case histories. Aphorisms lend
themselves to oral transmission they live in speech, not on
the page and the best and most memorable of them are like
poetry, the haiku of medicine. It is the oral-poetic nature of
a good aphorism, writes Quentin Shaw, that flash-welds it
into the memory [6]. The aphorism has persisted as a teach-
ing tool; consider three Hippocratic aphorisms [7], followed
by three that I memorized from my own medical training:
Dysentery, if it commence with black bile, is mortal.
In dropsical persons, ulcers forming on the body are not easily
healed.
In acute diseases, coldness of the extremities is bad.
The pain of biliary colic radiates to a point just below the right
scapula.
The sun should never set on an empyema.
Chest pain that is substernal, exertional, and relieved by nitroglyc-
erine is angina pectoris.
In the modern case report, it is still customary to conclude

the discussion with an aphoristic teaching point. As we sum
up the case, we invoke the authority of Hippocrates.
The Case Report in Ancient and Medieval Times 11
Galen (129ca.200 AD), the eminent Greek physician and

philosopher, took a very different approach to the case his-
tory. In contrast to the objective and detached case descrip-
tions of Hippocrates, Galen used the first person to place
himself at the center of his cases. His subjects were frequently
celebrities senators, philosophers, even the emperor and
he did not hesitate to describe his brilliance as a diagnosti-
cian, the gratitude of his patients, and the shortcomings of
other physicians. Regarding Galens first work, On the
Affected Parts, Cristina Alvarez Millan comments:
we have in these accounts mainly strange conditions and spec-
tacular cures, and more importantly, we also find the literary
device of increasing suspense throughout the nosological descrip-
tion, together with a remarkable amount of theatrical rhetoric.
Thus, a typical clinical account would be in the following
sequence: Galen's fear for the patient, Galen questioning the
patient, Galen puzzling over the disease, Galen coming to a con-
clusion (diagnosis or prognosis), Galen warning the patient,
Galen preventing his colleagues from administering a certain
treatment, Galen amazing everybody on the scene, Galen explain-
ing the real nature of the matter, and so on. [8]
Galen made many brilliant observations, and his medical

teachings were revered for more than a thousand years after
his death, until Vesalius and others began to disprove his
anatomical and physiological theories.
In the middle ages, European medical progress was ham-
pered by rampant scholasticism and religious proscriptions
against dissection and experimentation. As the Dark Ages
continued in Europe, Islamic medicine took the lead, most
impressively in the work and writings of Rhazes (865
925 AD) and Avicenna (9801037 AD). The case histories of
Rhazes stand out in particular for their accurate and insight-
ful descriptions of disease. Rhazes was the first to differenti-
ate smallpox from measles, and his explanation of why
survivors of smallpox are not infected a second time stands
as the first theory of acquired immunity [9]. In another case,
of a man who had fallen from a horse and sustained a neck
injury with loss of sensation in his third, fourth, and fifth
fingers, Rhazes was able to localize the lesion to the nerve
located after the seventh vertebra (i.e., C-8) [1]. Rhazes had
many students, and clearly used his case reports as didactic
tools; in many instances, he went beyond description to
include his own comparisons and generalizations from previ-
ous cases [10].
There was an interesting parallel rise of the case report in
both Europe and China in the late fifteenth century. The first
European collection of cases came from the Portuguese
Jewish physician Amatus Lusitanus, who published 700 cases
from 1551 to 1556. In China, the Stone Mountain Medical
Case Histories of Wang Ji, written up and published in 1531
by his disciple Chen Hue, comprised about 100 case histories
collected over 15 years. The early Chinese and European case
reports had similar formats, and served both to teach a wide
audience and to promote the doctors practices. An important
difference was that the Chinese case reports tended to put
respect for authority above experience, while the European
case reports emphasized experience and valued debate and
argument. Also, the Chinese physicians thought that case
reports were for patients as well as physicians, and functioned
as part of the treatment; European physicians saw them
chiefly as a way to communicate with each other about dis-
eases and treatments [11].
Origins of the Modern Case Report

The historian Gianna Pomata has traced the roots of the
modern case report to the Observationes (collections of case
histories), which originated in the second half of the sixteenth
century, and grew to become a primary form of medical writ-
ing by the eighteenth century [12]. The Observationes began
as a form of self-promotion for town and court physicians, but
eventually came to be viewed as a source of medical
knowledge. The original emphasis on therapeutic success,
writes Pomata, gave way to a new focus on the descriptive
knowledge of disease through detailed observation.
Origins of the Modern Case Report 13
As the Enlightenment eased religious restrictions, autopsy

findings began to be included in case reports, which improved
diagnostic accuracy and led to major advances in the study of
anatomy and physiology [13]. Pomata links the rise of the
case report with the new epistemological value of observa-
tion in the age of the Scientific Revolution [12]. From the
eighteenth century to the mid-twentieth century, even as it
continued to change and develop, the case report played a
critical role in teaching and discovery as well as in shaping the
day-to-day practices of physicians. This is not to say that the
case reports of 200 years ago were much like the objective
and detached reports of today; eighteenth and early nine-
teenth century authors still favored the conversational tone
of Galen, placed more emphasis on the patients subjective
experiences, and often employed dramatic devices to delay
the moment of diagnosis or heighten the narrative tension
[4]. Consider Dr. John Warrens description of a case in his
Remarks on Angina Pectoris (1812):
I had too soon an opportunity of confirming my suspicions; for on
the following Sunday, whilst attending public worship in Brattle
Street, Mr. Neal was seized with a most violent paroxysm, under
circumstances peculiarly affecting. In the midst of a discourse
highly interesting in its nature, and delivered with a great degree
of fervor, whilst the eyes of all were fixed upon the preacher, he
was observed to raise his hand, and forcibly rub his breast; his
voice faltered, and his countenance changed; and, after one or two
efforts to proceed, he sallied back on his seat, and became insen-
sible. [14]
In his Essay on the Shaking Palsy (1817), James Parkinson

brilliantly linked the disorders of trembling, posture, and gait
as a single disease entity. Here he describes the terminal
stages of the disease:
As the debility increases and the influence of the will over the
muscles fades away, the tremulous agitation becomes more vehe-
ment. It now seldom leaves him for a moment; but even when
exhausted nature seizes a small portion of sleep, the motion
becomes so violent as not only to shake the bed-hangings, but
even the floor and sashes of the room. The chin is now almost
immoveably bent down upon the sternum. The slops with which
he is attempted to be fed, with the saliva, are continually trickling
from the mouth. The power of articulation is lost. The urine and
fces are passed involuntarily; and at the last, constant sleepiness,
with slight delirium, and other marks of extreme exhaustion,
announce the wished-for release. [15]
Note the personification (exhausted nature) and the

sentimental wished-for release which further dramatize
Parkinsons compelling clinical observations. In a similar
vein, several eminent Victorian cardiologists used sensational
and sentimental language in their case reports as they
described the distressing effects of heart disease on their
patients and themselves [16].
But change was coming: the twentieth century saw the
depersonalization of case reports and the standardization of
their structure, with the rise of the now-familiar introduc-
tion/case report/discussion format and the gradual disap-
pearance of the author from the narrative [1]. Oslers 1902
report of two cases of intermittent claudication [17] is charac-
teristic of this modern transition point in the case report. He
begins with a recollection of a horse autopsy he had viewed
with some members of the Montreal Veterinary College
more than 20 years before. The horse had been afflicted with
a peculiar form of intermittent lameness, and the autopsy
showed verminous aneurysmsof the iliac arteries. He
cites the case of another horse that had to stop and rest after
being driven for fifteen or twenty minutes; autopsy showed
clots obstructing the arteries in both hind legs. He then gives
a thorough review of the literature, including a case reported
by Charcot in 1856 of a soldier with classic intermittent clau-
dication, who was found at autopsy to have a bullet encysted
near the iliac artery, which had caused an aneurysm with
obliteration of the lower part of the artery. Collateral blood
flow had allowed a modest level of activity, but more vigorous
activity caused ischemic pain that was relieved only with rest.
Osler then describes his own case of a young man with a
Origins of the Modern Case Report 15
syphilitic abdominal aortic aneurysm who developed leg

claudication symptoms after the aneurysm was successfully
treated with wiring and electrolysis:
After walking for a certain distance his legs would, as he
expressed it, give out completely; so that he could not move
another step, and had to sit down. After resting a few minutes he
could then go on again. This was more particularly noticeable
when he walked on the street. He had to go very slowly and could
not go for any distance. There was no paralysis accompanying the
loss of ability to walk. He could move his legs, but there was an
uncontrollable feeling that he could not take another step.
Accompanying this there was a sensation of dead, heavy weight
in the legs, but no cramps. Walking about in the house (and in the
yard) did not bring on the condition, but he had had it very fre-
quently in the past few months and he had learned to ward it off
by walking very cautiously and slowly and resting at intervals. The
femoral artery and the dorsal arteries of the feet were distinctly
sclerotic.
Osler concludes with an important teaching point:

As shown in the horse and in the first case which I here report,
the affection is not always due to simple arterio-sclerosis, but may
be due to aneurism, as in Charcots case and as is the rule in the
horse. [17]
In this terrifically interesting and entertaining interspecies

case report, Osler writes in the first person, and brings in his
odd (though very apt) experience in veterinary medicine. Yet,
this case report is distinctly modern in that it contains an intro-
duction, review of the literature, concise description of two
cases, and a strong teaching point. At the end, Osler cannot
resist adding a word as to the name, and indicates his prefer-
ence for the term intermittent claudication as opposed to
angiosclerotic intermittent dysbasia, intermittent muscle paresis,
or angiosclerotic paroxysmal myasthenia, as proposed by
Charcot, Erb, and Higier. This is the literary Osler expressing a
preference, which any reader of Aequanimitas will surely
respect. (Oslers paper brings to mind another interspecies case
report, recently published in the New England Journal of
Medicine, of an HIV-infected man who developed a nonhuman

malignancy that arose from proliferating, genetically altered
tapeworm cells. This was the first case of human disease caused
by transmissible clones of parasite-derived cancer cells [18]).
The Rise, Decline, and (Electronic) Rebirth

of the Case Report
Over the past 100 years, the popularity of the case report has
risen, fallen, and risen again. The twentieth century saw a
tremendous surge in the publication of case reports focusing
on new diseases, drug side effects, etiology and mechanisms
of disease, therapy, prognosis, and education [19]. New dis-
eases first described in case reports include shell shock
(1915), Cushings syndrome (1932), erythroblastosis fetalis
(1932), Ebola virus infection (1977), toxic shock syndrome
(1978), AIDS (1981), and thrombophilia due to Factor V
Leiden (1993). Significant drug side effects first described in
case reports include thalidomide-related birth defects (1961),
venous thrombosis due to oral contraceptives (1961),
chlorpropamide-induced SIADH (1970), valvulopathy asso-
ciated with weight-loss drugs (1996), and troglitazone-induced
liver failure (1998). Other landmark twentieth century case
reports include the first surgical ligation of a patent ductus
arteriosus (1939), the first use of lithium to treat mania
(1949), and the first heart transplant (1967). Physicians
looked to case reports for practical guidance, education, and
inspiration. Furthermore, they were frequently able to pub-
lish their own interesting cases; over the 30-year period, from
1946 to 1976, case reports comprised up to 38 % of all articles
published in general medicine journals [20].
The 1980s, however, marked the beginning of a steep
decline in the publication of case reports in many leading
journals. This decline correlated with a rise in the publication
of research articles (articles which included original,
The Rise, Decline, and (Electronic) Rebirth 17
firsthand data with a clearly delineated research methodol-

ogy), which increased from 50 % of all psychiatry journal
articles in 19691970 to 82.4 % by 19891990 [21]. Another
factor was the popularization and broad acceptance of evi-
dence-based medicine, which raised randomized controlled
trials to the pinnacle of the evidence pyramid, and vilified case
reports and case series as the lowest forms of intellectual life,
even lower than the case-control study [19]. In their excellent
article on the recent history of the clinical case report, Nissen
and Wynn [22] describe how the case report was marginalized
by editors, whether relegated to the Letters to the Editor
section, limited by stringent selection criteria, or, in many
cases, barred entirely from publication. Case reports are gen-
erally cited less often than clinical research studies, and the
increasing importance of the impact factor gave editors
another reason to avoid publishing them. In addition, the dra-
matic rise in government and pharmaceutical company fund-
ing of randomized controlled trials made the largely unfunded
case report a less desirable venue for both authors and jour-
nals [22]. All of these factors contributed to the flat overall
growth in case report publication from the 1980s through the
mid-1990s.
And then, in the late 1990s, the case report began to rise
again. A number of prestigious journals The Lancet, the
American Journal of Psychiatry, BMJ, the Journal of Clinical
Oncology, and others began to publish case reports again in
a variety of formats. Around the same time, some skeptics
began to criticize evidence-based medicine as a hierarchy of
clinical epidemiology that favors large-n quantitative stud-
ies to evaluate medical interventions with wide applicability,
but fails at the level of the individual patient [22]. In the
backlash against evidence-based medicine, interest began to
grow in the narrative of the individual patient, which could be
studied with qualitative research methods and applied to
other patients with similar patterns of illness. Between 2000
and 2013, the rate of PubMed-indexed case report publica-
tion increased by 36 %, from 42,000 to 58,000 per year.
Perhaps the most important factor in the case reports

revival has been the rise of the electronic case report journal.
This trend began in 2007, with the Journal of Medical Case
Reports, Cases Journal, and BMJ Case Reports; since then,
there has been exponential growth with more than 30 online
case report journals as of November, 2015. Increasingly, both
the advantages and problems of these online journals are
becoming more clear [23]. On the one hand, the case report
journal can be a gateway to publication and career advance-
ment for both busy clinicians and novices who lack experience
in medical writing. In areas of the world with limited resources,
where research funding is scarce, open-access case report jour-
nals can be a way to post important clinical findings and circu-
late medical information in the community. Another potential
benefit is the creation of a large database of cases, which in
theory could be useful in the diagnosis and treatment of indi-
viduals with complex and unusual problems not addressed by
clinical trials. On the other hand, the quality of both peer
review and writing has been inconsistent in some of these jour-
nals, with critical information missing, inadequate explanation
of events, and unsupported conclusions. Authorship fees can be
a hindrance to publication, especially for authors lacking insti-
tutional support, and the combination of high fees and sub-
standard peer review raises the specter of vanity publication
for those willing to pay. Finally, the large database of margin-
ally significant cases in online journals might drown key sen-
tinel events in a sea of careless publishing [23].
Several authors have proposed case report guidelines as a
solution to these problems [2325]. They suggest that guide-
lines could improve both the evidence value of individual
case reports and the quality of the database as a whole. The
authors of the CARE guidelines, a consensus-based case
report guideline and 13-point checklist first published in
2013, assert that the systematic aggregation of information
from case reports will inform clinical study design, provide
early signals of effectiveness and harms, and improve health-
care delivery [22]. This is an exciting development, but one
References 19
could argue that, with 1.77 million case reports already

indexed in PubMed, the guideline ship has already sailed.
Another approach might be to disseminate the CARE guide-
lines to all physicians in training and teach them to assess the
evidence value of each case report at the time it is accessed
for patient care.
But before we embrace strict guidelines, we should con-
sider what we have learned from the long history of the
medical case report. Case reports reflect the cultures, values,
and technologies of their times. Therefore, the form and
function of the case report must continue to change over
time. Who can imagine what medical case reports will look
like in 500 years? And why would these future case reports
adhere to twenty first century guidelines, any more than we
look to the sixteenth century for instruction? The other dis-
tinctive thing about case reports is that they are at their best
highly creative endeavors, bursting with enthusiasms, intu-
itions, and hypotheses that are barely restrained by the tra-
ditional form. Is there a place within the guidelines for
Oslers stiff-legged horses, or for Rhazes intuitive hypothe-
sis on immunity, which was correct but remained unverifi-
able for centuries? Whatever guidelines we choose, we must
not stifle speculation, which is essential not only in case
reporting but in all medical writing.
References
1. Nissen T, Wynn R. The history of the case report: a selective
review. JRSM Open. 2014;5(4):2054270414523410.
2. Frank LL. Diabetes mellitus in the texts of old Hindu medicine
(Charaka, Susruta, Vagbhata). Am J Gastroenterol. 1957;27(1):
7695.
3. Allen JP. The art of medicine in ancient Egypt. The Metropolitan
Museum of Art, New York. New Haven/London: Yale University
Press; 2005.
4. Hurwitz B. Form and representation in clinical case reports. Lit
Med. 2006;24:21640.
5. The Internet Classics Archive. Hippocrates: of the epidemics

(trans. Francis Adams). 1994. http://classics.mit.edu/Hippocrates/
epidemics.html. Accessed 29 Oct 2015.
6. Shaw Q. On aphorisms. Br J Gen Pract. 2009;59(569):9545.
7. The Internet Classics Archive. Hippocrates: aphorisms (trans.
Francis Adams). 1994. http://classics.mit.edu/Hippocrates/apho-
risms.html. Accessed 13 Nov 2015.
8. Alvarez MC. Graeco-Roman case histories and their influence on
Medieval Islamic clinical accounts. Soc Hist Med. 1999;12:1943.
9. Ashtiyani SC, Amoozandeh A. Rhazes diagnostic differentiation
of smallpox and measles. Iranian Red Crescent Med J. 2010;
12(4):4803.
10. Alvarez MC. The case history in Medieval Islamic medical litera-
ture: Tajarib and Mujarrabat as source. Med Hist.
2010;45(2):195214.
11. BMJ Blogs. Richard Smith: case reports in 16th century Europe
and China. Blogs.bmj.com/2013/07/09/richard-smith-case-
reports-in-16th-century-europe-and-china/. Accessed 29 Oct
2015.
12. Pomata G. Sharing cases: the observations in early modern medi-
cine. Early Sci Med. 2010;15(3):193236.
13. King LS, Meehan MC. A history of autopsy. A review. Am
J Pathol. 1973;73:51444.
14. Warren J. Remarks on angina pectoris. N Engl J Med.
1812;1(1):111.
15. Parkinson J. Project Gutenbergs An Essay on the Shaking Palsy.
www.gutenberg.org/files/23777/23777-h/23777-h.htm. Accessed 3
Nov 2015.
16. Class M. Introduction. Medical case histories as genre: new
approaches. Lit Med. 2014;32(1):viixvi.
17. William Osler: Original Papers 18981906. Intermittent claudi-
cation, 1902. digitalcommons. library.tmc.edu/osler/2/. Accessed
3 Nov 2015.
18. Muehlenbachs A, Bhatnagar J, Agudelo CA, et al. Malignant
transformation of Hymenolepsis nana in a human host. N Engl
J Med. 2015;373(19):184552.
19. Vandenbroucke JP. Case reports in an evidence-based world. J R
Soc Med. 1999;92(4):15963.
20. Fletcher RH, Fletcher SW. Clinical research in general medicine
journals. A 30-year perspective. N Engl J Med. 1979;301:1803.
References 21
21. Pincus HA, Henderson B, Blackwood D, Dial T. Trends in

research in two general psychiatric journals 19691990: research
on research. Am J Psychiatry. 1993;150:13542.
22. Nissen T, Wynn R. The recent history of the clinical case report:
a narrative review. J R Soc Med Sh Rep. 2012;3:87.
23. Sun GH, Oluseyi A, Hayward RA. Open access electronic case
report journals: the rationale for case report guidelines. J Clin
Epidemiol. 2013;66(10):106570.
24. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines:
consensus-based clinical case reporting guideline development.
J Med Case Rep. 2013;7:223.
25. Rison RA. A guide to writing case reports for the Journal of
Medical Case Reports and Biomed Central Research Notes.
Chapter 3
The Educational Value
of Case Reports
Clifford D. Packer
Educational Benefits of Reading

Case Reports
A case report is a clear, concise, and digestible account of a

case that can easily be read in one sitting. It offers much more
than a description of a unique or unusual patient encounter.
A well-prepared case report gives a focused review of the
pertinent literature, places the case in context compared with
other similar cases, proposes a hypothesis to explain what
occurred, and makes a clear teaching point. The attentive
reader will gain both deeper understanding of the topic area
and insight into specific points of diagnosis and management.
Consider, for example, a case report written by one of my
former medical students describing an unusual case of airway
compromise in infectious mononucleosis [1]. We learn that
infectious mononucleosis can, in rare cases, cause life-
threatening airway obstruction due to severe tonsillar hyper-
trophy, with the key findings of hot potato voice and
kissing tonsils on CT imaging of the neck (Fig. 3.1). In
addition, we learn that the differential diagnosis for pharyn-
geal airway obstruction also includes peritonsillar abscess,
epiglottitis, Ludwigs angina, angioedema, foreign body, neo-
plasm, and local trauma. A literature review reveals that only
5 of 467 mononucleosis patients in one series had airway

DOI 10.1007/978-3-319-41899-5_3
24 Chapter 3. The Educational Value of Case Reports
Figure 3.1 CT image of kissing tonsils [1]
compromise, that most patients with it respond well to

corticosteroids, and that very few require tonsillectomy.
Finally, the author clearly delineates the clinical reasoning
that led to the diagnosis:
While this patient already carried a diagnosis of infectious mono-
nucleosis, we could rule out diphtheria as there were no signifi-
cant pharyngeal exudates and he had been previously vaccinated.
Direct visualization of the pharynx with laryngoscopy revealed
no foreign bodies, neoplasms, abscesses, and revealed only tonsil-
lar swelling. Cultures for superimposed streptococcus infection
were negative. Taken together, these diagnostic findings further
confirmed that this patients symptoms were due only to infec-
tious mononucleosis without exacerbating processes. [1]
Educational Benefits of Reading Case Reports 25
Thus, in a three-page case report that can be read in less

than 10 minutes, the reader learns key points on the differen-
tial diagnosis, etiology, epidemiology, diagnostic work-up,
imaging findings, and management of pharyngeal obstruction
from mononucleosis.
Consider also a 2014 case report by Kreuels et al., A case
of severe Ebola virus infection complicated by gram-negative
septicemia [2]. This report meticulously describes the care of
a patient with Ebola infection complicated by septicemia,
respiratory failure, paralytic ileus, and encephalopathy, who
was successfully treated with general intensive care measures.
The patient put out 48 l of diarrhea per day over the first 72
h, and required 10 l of IV fluid per day along with aggressive
potassium repletion. A table gives the 27-day record of vital
signs, oxygenation, IV and PO fluid intake, fluid losses from
diarrhea and vomiting, urine output, fluid balance, and labo-
ratory test results. There are two figures: a timeline with
plasma viral RNA levels, white blood cell count, CRP levels,
and antimicrobial treatment (Fig. 3.2); and a second timeline
with antibody titers in plasma, and viral RNA load in plasma,
sweat, and urine. The practical educational value of this case
report is tremendous. First, it documents the natural history
of Ebola virus infection. Second, it gives a comprehensive
description of a successful treatment regimen, including
details of critical infection control measures, which serves as
a blueprint for the treatment of other patients. Third, based
on the case and their review of the literature, the authors
propose certain basic principles in the care of Ebola patients:
the vital importance of aggressive IV hydration, the use of
serial ultrasonography and other tests to document the ade-
quacy of hydration, and the need to monitor patients for signs
of superimposed bacterial infection by means of laboratory
tests, such as C-reactive protein. Practical management points
and discussion of the clinical decision-making are defining
features of case reports [3, 4]. In this case, in the absence of
randomized controlled trials, we are given some of the best
available evidence on optimal treatment of Ebola virus
infection.
8 30
Plasma
viral RNA
25
7
20
Log10 viral RNA (copies/ml)
White cells (x103/mm3)

6 Blood
culture
taken
15
White cells
5
10
4 Meropenem and vancomycin

5
Ceftriaxone
3 0
13 43 123 65 60 37 33 30 37
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
Day of illness
Figure 3.2 Timeline of plasma viral RNA load, septicemia, and

antimicrobial therapy in a patient with severe Ebola virus disease
[2] (Copyright 2014 Massachusetts Medical Society. Reprinted
with permission from Massachusetts Medical Society)
Case reports also create recognition patterns that can

help clinicians to identify and treat rare and unexpected con-
ditions in their own practices [5], and can be invaluable to
physicians confronted with cases that defy the usual diagnos-
tic and treatment algorithms. I once admitted an elderly man
to the hospital with weight loss and failure to thrive; his PSA
was 200, and a biopsy confirmed prostate cancer. His meta-
static work-up revealed multiple pulmonary nodules but no
bone or liver metastases. I consulted a pulmonologist who
recommended a bronchoscopic biopsy. However, a literature
search turned up several cases of men with prostate cancer
metastatic only to the lungs, all of whom had complete
regression of their lung nodules with hormonal therapy.
Based on this evidence, we decided to cancel the bronchos-
copy and proceed with treatment [6]. This case illustrates the
Educational Benefits of Writing Case Reports 27
practical educational value of reading case reports, especially

for the evaluation and treatment of patients who do not pres-
ent with the usual textbook symptoms.
Educational Benefits of Writing Case Reports

for Medical Students and Residents
A few authors have discussed the educational benefits of

publishing case reports for medical students and residents. In
their article The case report in context, Carleton and Webb
comment that the experience of writing a case report can
sharpen authors writing skills, lend critical experience in the
peer review process, and prepare medical professionals for
careers as scholarly clinicians [5]. Petrusa and Weiss explore
the benefits of collaborative writing of case reports with
residents: extending patient care activities to a more scholarly
product, improving residents writing and critical thinking
skills, facilitating fellowship and academic career plans, and
documenting faculty teaching efforts, with the published case
report as tangible evidence of teaching [7]. McNeill et al.
developed a series of tutorials to teach junior doctors the
principles of medical publishing and academic writing, which
included editorial comments on structure and content, per-
fection of drafts via e-mail correspondence, and advice on
journal selection. Their aim was to combine formal teaching
on medical publishing with the experiential learning of writ-
ing a case report in order to develop the skills required to
produce publications and thus enhance career prospects [8].
As an internal medicine clerkship director, I have become
increasingly aware of the many educational benefits of case
reporting; consequently, I have required all of my students to
write a case report over the past 7 years. Early in the clerkship,
we meet for a 1-hour session to discuss the evidence value of
case reports, how to select a case, and how to structure and
present the report, which must be at least 400 words with two
to three references. In the sixth week, we meet again and the
students present their case reports to the group, respond to

questions, and receive feedback. All students have completed
the assignment, and most are able to select a suitable case and
write a well-reasoned discussion without my assistance. To
date, this project has produced more than 250 case reports, 35
ACP and SGIM abstracts, and 15 published case reports in
peer-reviewed general medicine, pharmacology, and psychia-
try journals. Student case report topics [9] have included:
Transient transcortical motor aphasia caused by lithium
toxicity
Sphingomonas paucimobilis bacteremia in a patient with
alcoholic cirrhosis
MSSA-associated metastatic endophthalmitis
Left atrial invasion of squamous cell lung cancer
Diclofenac-associated neutropenia
Pylephlebitis associated with necrotizing pancreatitis and
prostatic abscesses
Pantoea agglomerans bacteremia from a rose thorn injury
Prostate cancer metastatic to the clivus, presenting as epi-
sodic diplopia
Elephantiasis nostras verrucosa in a 62-year-old man with
chronic lymphedema
Occult Citrobacter freundii bacteremia in a man with
cirrhosis
Ipilimumab-induced pan-colitis
Type B lactic acidosis caused by metastatic gastric
carcinoma
Cannabinoid hyperemesis syndrome
Cushings syndrome due to an interaction between oral
budesonide and ritonavir
Concurrent reactive arthritis, Graves disease, and warm
autoimmune hemolytic anemia
Xanthogranulomatous pyelonephritis presenting as fever
of unknown origin
MERS (mild encephalitis with a reversible splenial lesion)
in the setting of Legionella pneumonia and B12
deficiency
Educational Benefits of Writing Case Reports 29
Of note, 14 of the 15 students who published their case

reports required the help of faculty mentors as co-authors;
only one student was able to publish as a single author [1].
Since case reports often require multiple revisions before
publication, co-authoring with students typically involves
several months of mentoring, with much back-and-forth dis-
cussion. In almost all cases, the learning is bidirectional, the
mentoring is deeply appreciated, and the door is left open for
new collaborations after the case report is published.
Over time, it has become increasingly clear that my stu-
dents are learning many useful skills as they select, research,
and write up their case reports. Case selection is a complex
process that involves advanced observation and pattern-
recognition skills. Generation of a hypothesis to explain
unusual events requires thorough research, clear understand-
ing of pathophysiology, and a dash of creativity. Writing a
case report demands rhetorical versatility an ability to
combine the narrative and descriptive elements of the case
description with the synthetic and argumentative elements of
the discussion. In addition, case reports are patient-centered
because they tell patients stories even as they seek to com-
prehend and explain their illnesses; students can be taught to
consider (and connect) both the scientific and humanistic
aspects of their patients through case reports [10].
My students have shown impressive creativity and
resourcefulness in developing their hypotheses. One student,
for example, had a patient with an atypical presentation of
Behcets syndrome with renal infarcts and orogenital ulcers.
The patient also had a chart history of Ebsteins anomaly, but
had been healthy enough to serve as an active duty soldier,
which made the student wonder if he had been misdiagnosed.
A literature search revealed that Behcets-associated endo-
myocardial fibrosis can mimic Ebsteins anomaly, and the
student hypothesized that Behcets explained the right atrial
and tricuspid valve abnormalities seen on echocardiogram.
This surmise was confirmed when old surgical records were
reviewed.
Educational Benefits of Writing Case Reports

for Practicing Physicians
Sir William Osler, the famed Canadian physician, founded

the modern teaching service at Johns Hopkins University,
wrote the last single-author medical textbook, and became
Regius Professor of Medicine at Oxford. Dr. Osler published
more than 180 case reports, and had this advice for his fellow
physicians: Always note and record the unusualPublish it.
Place it on permanent record as a short, concise note. Such
communications are always of value [11]. Regarding medical
writing and publication, he added:
The difficulty is that the young write too much, the mature write
too little. There is too much green fruit sent to market, and the
fruit of too many of the fine trees is never plucked at all [12]
Osler felt that mature physicians have an obligation to

publish, in order to share their important clinical observa-
tions and insights with others. The problem, of course, is that
practicing physicians are usually far too busy (or feel they are
too busy) to write case reports on their patients. Also, com-
munity physicians, although they generally see more patients,
may be less confident than academic physicians in their abil-
ity to publish. It is our contention that any physician with a
sufficiently novel case can and should be able to publish it.
The benefits of publication include the expertise gained from
thoroughly researching a rare case, the opportunity to dis-
seminate ones observations or innovations to a wider audi-
ence, and the scholarly connection with all physicians, past
and present, who have written case reports. The knowledge
that one has placed a brick or two at the base of the evidence
pyramid (or added an apple to the bushel, to complete
Oslers metaphor) can be profoundly satisfying, especially as
the citations begin to roll in. Our chief aim with this book is
to help all physicians to comply with Oslers archival impera-
tive: Always note and record the unusualPublish it.
References 31
References
1. Kakani S. Airway compromise in infectious mononucleosis: a
case report. Cases J. 2009;2:6736.
2. Kreuels B, Wichmann D, Emmerich P, et al. A case of severe
Ebola virus infection complicated by gram-negative septicemia.
N Engl J Med. 2014;371:2394401.
3. Aitken LM, Marshall AP. Writing a case study: ensuring a mean-
ingful contribution to the literature. Aust Crit Care.
2007;20(4):1326.
5. Carleton HA, Webb ML. The case report in context. Yale J Biol
Med. 2012;85(1):936.
6. Packer CD. The MEDLINE search as a diagnostic maneuver.
Arch Intern Med. 2005;165(6):7037.
7. Petrusa ER, Weiss GB. Writing case reports: an educationally
valuable experience for house officers. J Med Educ.
1982;57(5):4157.
8. McNeill A, Parkin CK, Rubab U. Using a case report to teach
junior doctors about medical publishing. Med Teach.
2007;29(5):511.
9. Packer CD. Case reports: good evidence, good for teaching.
SGIM Forum. 2014;37(8):10, 14.
10. Packer CD, Katz RB, Krimmel JD, Iacopetti CL, Singh MK. A case
suspended in time: the educational value of case reports. Acad
Med. 2016. PMID:27097050. doi:10.1097/ACM.0000000000001199.
[Epub ahead of print].
11. Thayer WS. Osler, The Teacher Sir William Osler, Bart. Baltimore:
Johns Hopkins Press; 1920. p. 512.
12. Osler WD. Johnston as physician. Washington Med Ann.
1902;1:15861.
Chapter 4
Practical Benefits of Case
Reporting
Gabrielle N. Berger
Introduction
Case reports represent an important avenue for clinicians

aiming to disseminate novel observations to a broad audi-
ence. The value of case reports has been contested in recent
decades, in part due to an increased focus on publishing sci-
entific papers that bolster a journals impact factor [1].
Despite this trend, case reports remain an accessible and
achievable mechanism for many practitioners to publish. This
is particularly true for trainees and junior faculty seeking
publications for career advancement but who lack the
research skills to execute a sophisticated research study [2, 3].
This chapter will address the practical benefits of case report-
ing with a particular focus on the role of case reports in
enhancing the medical literature, patient care, and career
development.
Contribution to the Medical Literature

For centuries, case reports occupied a highly respected place in
the medical literature [4] (see Chap. 2). With its roots planted
in the Greek classical era, the modern case report evolved
as a critical mode of communication to help practitioners

DOI 10.1007/978-3-319-41899-5_4
34 Chapter 4. Practical Benefits of Case Reporting
exchange knowledge about pathophysiology and disease.

Fundamentally, case reports are based on observations: they
allow medical practitioners to catalog their experiences with
unusual presentations of disease, innovative surgical and pro-
cedural techniques, and the effects of new drugs [5].
While medical case reporting gained relevance for centu-
ries, the emergence of evidence-based medicine ushered in a
new era focused on large-scale research to inform clinical
care. Within this context, levels of evidence are stratified
according to strength and rigor, with systematic reviews and
randomized controlled trials occupying the apex of the
evidence-based pyramid, while expert opinion, case reports,
and case series form the base [6] (see Fig. 4.1). This paradigm
shift, with its move away from observational data to guide
clinical decision-making, led many to reconsider the merit of
case reports. Indeed, the number of case reports published in
high-impact journals declined dramatically over the last sev-
eral decades [1]. Case reports are less likely to be cited as
frequently as large research studies, which can adversely
affect a journals impact factor [7]. Because journals gener-
ally strive for the highest possible impact factor, editors are
often reluctant to publish case reports fearing a decline in
ratings.
Systematic
Reviews
Randomized
Trials
Cohort Studies
Case Control Studies
Case Series, Case Reports
Animal Research/Expert Opinion
Figure 4.1 The hierarchy of evidence

The Case For Guidelines 35
Although observational and even anecdotal in nature

case reports and case series remain a critical plank in the
platform of evidence-based medicine. Publication of novel
disease presentations and treatment effects spur additional
research and may highlight the emergence of new trends or
patterns of disease [8]. Consider the report of five gay men
with Pneumocystis pneumonia in a 1981 Morbidity and
Mortality Weekly Report (MMWR) published by the Centers
for Disease Control (CDC) [9]. This publication was among
the first to describe the new disease that came to be known as
the acquired immune deficiency syndrome (AIDS). Further,
the association between specific opportunistic infections and
HIV was first described in case reports, including HIV-related
Kaposis sarcoma [10] and retinitis due to cytomegalovirus
[11]. Even today, highly respected journals publish case
reports or series when new diseases are identified. Examples
include the emergence of zoonotic Onchocerca lupi infection
in the United States [12], or when a previously known disease
entity poses a new public health risk, as in the case of variant
Creutzfeldt-Jakob disease transmission by blood transfusion
[13]. These examples highlight the contributions of case
reporting to the medical literature: without the ability to rap-
idly disseminate new medical observations through case
reports and series, there is limited evidence to inform larger,
more rigorous studies (see Fig. 4.2, adapted from Pierson [7]).
The Case For Guidelines

Case reporting as a mechanism for launching future paths of
scientific inquiry has been well described [7, 14]. However,
there is general agreement that case reports must be suffi-
ciently rigorous in methodology and reporting standards to
influence advanced research studies. Reporting guidelines
exist for other study designs, including randomized controlled
trials (CONSORT) [15], systematic reviews and meta-
analyses (PRISMA) [16], and adverse event case reports [17].
Recent evidence suggests that journals employing the
CONSORT guidelines receive randomized controlled trial
submissions that are more complete [18].
b Physiologic Clinical Trail c

Studies
Clinical Trail
Clinical Trail
Observation
a Documentation
Hypothesis Generation
Interpretation in
Clincal Context d
Incorporation into
Clinical Practice
Fig. 4.2 How the observation and documentation of an individual

case can lead ultimately to changes in practice. Although it is possi-
ble to speculate about mechanisms and the potential for broader
application of what happened in a single case, justification for
changing the future care of patients requires many more steps and
substantially higher levels of evidence than can be derived from one
experience
Until recently, there was no similar set of guidelines for

case reports. However, the emergence of online outlets for
publishing case reports and an interest in increasing the qual-
ity of case report submissions led an interdisciplinary team of
clinicians and researchers to publish the CARE (CAse
REport) guidelines in 2013 [14]. The CARE guidelines pro-
vide a checklist for authors to capture key clinical data and
translate that data into a concise, evidence-driven case report.
Consisting of 13 discrete items, the checklist aims to help
authors structure the case report writing process. Adoption of
the CARE guidelines or another standardized framework is
likely to improve the completeness of case reports and may
help reestablish case reporting as a more respected compo-
nent of the medical literature.
Contribution to Patient Care 37
Contribution to Patient Care
Case reports benefit patients directly by allowing clinicians

to share clinical experiences that diverge from the standard
of care. While most practicing physicians aspire to apply
evidence-based medicine in their daily practice, there will
always be patients who fall into the gray zone of medi-
cine. For example, a patient may present with a confusing
constellation of symptoms that does not fit with a known
syndrome. In these scenarios, there is often a lack of evi-
dence to guide clinical decision-making. The physicians
ability to compare the patients presentation to previous
case reports can mean the difference between making a
diagnosis and leaving a patient searching for additional
answers.
The limitations of evidence-based medicine often emerge
when patients face decisions about pursuing aggressive treat-
ment, some of which may have significant side effects [5].
Depending on individual goals regarding quality of life,
patients may decline a recommended treatment plan despite
counseling from their physician about the benefits. In this
situation, physicians should use the literature to identify addi-
tional treatment options for the patient. Case reports docu-
menting how a physician chose an alternative therapy and
the outcome of that therapy can help align their recommen-
dations with the patients preferences [19].
In the absence of clear guidelines for managing a particu-
lar disease, case reports can help illustrate the complex
decision-making process undertaken by other clinicians in
similar scenarios. Gaining insight into how colleagues grapple
with challenging clinical questions can validate a physicians
own internal struggle over how best to advise a patient. This
holds particular relevance for physicians who operate in iso-
lated areas and may not have access to consultation from
colleagues or subspecialists.
Despite the growing reliance on evidence-based medi-
cine to inform daily practice, many patients do not follow
the textbook in either their presentation or treatment
preferences. Knowing where to turn for advice in these

situations is essential for physicians aiming to improve care
for their patients. Accessing additional clinical experience
through case reports remains an invaluable resource for
clinicians seeking guidance outside the traditional evidence
base.
Career Enhancement
Case reports provide a practical, achievable avenue for schol-
arship for physicians at various stages of training. Many
learners and junior faculty aspire to publish in the medical
literature to demonstrate academic productivity. Yet medical
writing is a skill that must be practiced and honed over time:
learning to construct a well-written research manuscript is an
iterative process that requires mentorship and tenacity. It
also requires a significant amount of time and commitment.
Additionally, the likelihood that a manuscript will be accepted
for publication often correlates with an authors level of
experience publishing in the medical literature. Authoring
case reports is an effective way of gaining experience with
medical writing and can influence the success of publishing
future research projects.
Publishing case reports can be of particular benefit for
medical students and residents (see Chap. 3). Case reports
are brief; they do not require a background in research meth-
odology or primary data analysis skills. Although it takes
preparation and forethought to effectively organize a case
report project, writing a case report is a much more attain-
able goal than trying to spearhead a rigorous research manu-
script. In a survey of internal medicine residents who
presented work at a national meeting, the median time spent
preparing a case report was 50 hours, compared with 200 hours
for research abstracts [20].
Medical students just embarking on their careers typically
bring a high level of energy and enthusiasm to patient care.
Career Enhancement 39
They are often highly motivated to participate in a case

report project that validates this excitement. Case reports are
an ideal project for a medical student to lead: the scope of the
project is limited but provides an opportunity to develop a
range of important research skills, including [21]:
Conducting a literature search;
Constructing an abstract;
Writing a manuscript that adheres to journal expectations;
Engaging in multiple rounds of editing with a mentor;
Navigating the submission and review process.
Publishing in the medical literature as a student or resident
demonstrates intellectual curiosity, a commitment to scientific
inquiry, and the ability to follow-through on scholarly projects.
Committing to a case report project may be more pragmatic
than trying to submit a research manuscript, particularly
because it is easier to complete a case report on a limited
timeline. The likelihood of project completion is important
since a track record of successful publications makes learners
more attractive candidates for residency and fellowship.
Scholarship is also required for academic promotion. For
faculty pursuing a clinician-educator track (or similar path-
way) within an academic institution, publishing case reports
can help fulfill promotion and advancement criteria. With the
exception of pure research tracks at academic medical cen-
ters, many promotion committees recognize publication of a
case report as a valuable contribution to the literature. Case
reports should be listed as a published work on the curricu-
lum vitae, particularly if the report appears in a peer-reviewed
journal. Serving as the first or last author on a case report can
be particularly beneficial. As first author, the faculty member
is viewed as the project lead the person responsible for
most of the writing and moving the project toward completion.
In contrast, as last author, the faculty member fulfills the role
of project mentor. In this position, the faculty member pro-
vides leadership, oversight, vision, and mentorship for junior
colleagues.
Finally, publishing a case report allows a faculty member

to develop expertise in a particular condition or disease pre-
sentation [2]. The corresponding author may receive inquiries
from all over the world regarding similar presentations that
other clinicians have struggled with. This correspondence
may offer opportunities for collaboration with colleagues at
other institutions. Thus, a project that began as a single case
report may turn into a case series, which could then form the
foundation for larger research studies. This trajectory is just
one example of how a case report can serve as a springboard
for future scientific inquiry.
Conclusion
Case reports remain a critical component of the medical lit-
erature, offering many practical benefits for clinicians,
patients, and those eager to gain experience with medical
writing. Case reports form the foundation of the evidence-
based pyramid; they shed light on new disease entities,
emerging patterns of disease, potential side effects of drugs,
and alternative treatment options for patients whose goals
may differ from the standard of care. Case reports also repre-
sent an accessible pathway for learners and junior faculty to
publish in the medical literature, which is a key component of
academic advancement and promotion. While the role of
scientific research in informing medical practice cannot be
understated, case reports should be similarly valued as an
essential component of the medical literature.
References
1. Warner JO. Case reportswhat is their value? Pediatr Allergy
Immunol. 2005;16(2):934. doi:10.1111/j.1399-3038.2005.00266.x.
2. Bhattacharrya S, Miller J, Ropper AH. The case for case reports.
Ann Neurol. 2014;76(4):4846. doi:10.1002/ana.24267.
References 41
3. Stephens J, Wardrop R. Scholarship improved by case report

curriculum. Clin Teach. 2016. doi:10.1111/tct.12460.
4. McCarthy LH, Reilly KEH. How to write a case report. Fam
Med. 2000. doi:10.1136/bmj.327.7424.s153-a.
5. Nissen T, Wynn R. The clinical case report: a review of its merits
and limitations. BMC Res Notes. 2014;7:264.
6. Honeybul S, Ho KM. The role of evidence based medicine in
neurotrauma. J Clin Neurosci. 2015;22(4):6116.
7. Pierson DJ. How to read a case report (or teaching case of the
month). Respir Care. 2009;54(10):13728. http://www.ncbi.nlm.
nih.gov/pubmed/19796418. Accessed 16 Mar 2016.
8. Albrecht J, Meves A, Bigby M. Case reports and case series from
Lancet had significant impact on medical literature. J Clin
Epidemiol. 2005;58(12):122732. doi:10.1016/j.jclinepi.2005.
04.003.
9. Centers for Disease Control (CDC). Pneumocystis pneumonia
Los Angeles. MMWR Morb Mortal Wkly Rep. 1981;30(21):
2502. http://www.ncbi.nlm.nih.gov/pubmed/6265753. Accessed
25 Mar 2016.
10. Dotz WI, Berman B. Kaposis sarcoma, chronic ulcerative herpes
simplex, and acquired immunodeficiency. Arch Dermatol.
1983;119(1):934. http://www.ncbi.nlm.nih.gov/pubmed/6849574.
Accessed 22 Mar 2016.
11. Bachman DM, Rodrigues MM, Chu FC, Straus SE, Cogan DG,
Macher AM. Culture-proven cytomegalovirus retinitis in a
homosexual man with the acquired immunodeficiency syn-
drome. Ophthalmology. 1982;89(7):797804. http://www.ncbi.
nlm.nih.gov/pubmed/6289217. Accessed 22 Mar 2016.
12. Cantey PT, Weeks J, Edwards M, et al. The emergence of zoo-
notic onchocerca lupi infection in the United States a case-
series. Clin Infect Dis. 2015:civ983. doi:10.1093/cid/civ983.
13. Wroe SJ, Pal S, Siddique D, et al. Clinical presentation and pre-
mortem diagnosis of variant Creutzfeldt-Jakob disease associated
with blood transfusion: a case report. Lancet (London, England).
2006;368(9552):20617. doi:10.1016/S0140-6736(06)69835-8.
14. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D.
The CARE guidelines: consensus-based clinical case report
guideline development. J Clin Epidemiol. 2014. doi:10.1016/j.
jclinepi.2013.08.003.
15. Schulz KF. CONSORT 2010 statement: updated guidelines for
Reporting Parallel Group randomized trials. Ann Intern Med.
2010;152(11):726. doi:10.7326/0003-4819-152-11-201006010-00232.
16. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting

items for systematic reviews and meta-analyses: the PRISMA
statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.
pmed.1000097.
17. Kelly WN, Arellano FM, Barnes J, et al. Guidelines for submit-
ting adverse event reports for publication. Drug Saf.
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18. Turner L, Shamseer L, Altman DG, Schulz KF, Moher D. Does
use of the CONSORT Statement impact the completeness of
reporting of randomised controlled trials published in medical
journals? A Cochrane review a. Syst Rev. 2012;1. doi:10.1186/
2046-4053-1-60.
19. Browman GP. Essence of evidence-based medicine: a case
report. J Clin Oncol. 1999;17:196973.
20. Rivera JA, Levine RB, Wright SM. Brief report: completing a
scholarly project during residency training perspectives of
residents who have been successful. doi:10.1111/j.1525-1497.
2005.04157.x.
21. Pierson DJ. Case reports in respiratory care. Respir Care.
2004;49(10):118694.
Chapter 5
Is My Case Good Enough?
Introduction
A common barrier in writing a case report is the authors lack

of confidence that the case is novel enough to warrant publi-
cation. The reality is that most cases will be of interest to
someone, somewhere (see Chap. 11 for details on finding a
journal for your report). Even with this knowledge, it is
tempting to forgo the effort required to write and submit a
case report manuscript when there is uncertainty regarding
its value. This chapter reviews commonly held criteria regard-
ing the suitability of a case for publication and provides a
stepwise process to assess your case.
What Makes a Good Case?

Many physicians and journal editors have opined on what
criteria should be met for a case to be a published as a case
report. A helpful summary comes from an article entitled
Two cheers for case reports [1]. In this 2014 article, the
Scientific Editor of the Canadian Family Physician suggests
six types of cases that the journal would consider publishing:
Unusual or unexpected presentations of commonly seen
illnesses

DOI 10.1007/978-3-319-41899-5_5
44 Chapter 5. Is My Case Good Enough?
New associations or variations in disease processes

Presentations, diagnoses, or management of new or emerg-
ing diseases
An unexpected event in the course of treating or observ-
ing a patient
Unreported or unusual adverse effects or interactions of
medications
Novel or useful approach to managing patients with com-
plex chronic conditions
This is an exceedingly helpful list for authors considering

the suitability of a case for publication. Several important
points are highlighted: first, the disease process itself need
not be rare uncommon manifestations or complications of
common conditions can be very interesting and have great
educational merit. Second, regardless of the rarity of a dis-
ease, there is additional value in sharing observations about
caring for the patient, particularly when unexpected events
occur or novel approaches are taken.
Another article presenting tips on How to write a case
report details the characteristics that may make cases more
likely to be published [2]:
Cases that contribute to a change in the course of medical
science
Cases that illustrate a new principle or support or refute a
current theory and thus may stimulate research
Cases that present a therapeutic or diagnostic observation
that elucidates a previously misunderstood clinical condi-
tion or response
Cases that demonstrate an adverse response to drug thera-
pies or presumed cause-and-effect presentations that have
not been detected or reported
An unusual combination of conditions, cascading events,
or presenting complaints that confused the decision-
making process or created treatment dilemmas
A new observation of the impact of one disease process
or condition on another, or of a treatment regime for
one condition that results in an unexpected outcome of
a different condition
What Makes a Good Case? 45
Reports that describe the personal influence a particular

event had on the patient, the physician, or both
While some of these criteria may seem unattainable at first

glance, consider that it was a 1981 report on five patients with
Pneumocystis pneumonia published in the Centers for Disease
Controls Morbidity and Mortality Weekly Report [3] that
helped precipitate the recognition of the emerging syndrome
of acquired immunodeficiency syndrome (AIDS). An essay
on the shaking palsy by Dr. James Parkinson led to defining
the disease that now bears his name [4]. All clinicians are
faced with atypical presentations and clinical conundrums
during their career; it is not unrealistic to imagine that your
unusual case might someday contribute to a change in the
course of medical science.
Several themes begin to emerge when considering these
two sets of criteria. First, adverse events are of particular
interest to journal editors and other clinicians. From the per-
spective of patient care, learning about adverse events is criti-
cal to improving practice and preventing future occurrences.
Second, interesting or novel processes of care whether or
not they are accompanied by unexpected outcomes are
often excellent case reports. Looking beyond the disease to
consider how a physician arrived at a particular diagnostic or
treatment decision can inform colleagues facing similar clini-
cal scenarios. Finally, case reports that specifically consider
management questions can be similarly useful. Novel thera-
peutic strategies fall into this category, for example, the
approach detailed in the recent article entitled I cannot
stand this anymore! Chronic cortical stimulation for intrac-
table focal reflex epilepsy in the Neurological Picture series
in the Journal of Neurology, Neurosurgery and Psychiatry [5].
Finally, these lists allude to the concept of physician reflec-
tion, specifically, how medical events may shape personal or
professional trajectories. There is growing interest in publish-
ing reflection or perspective pieces, which are now com-
monly featured in some of the most high-impact medical
journals including the New England Journal of Medicine
(NEJM), the Journal of the American Medical Association
(JAMA), and The Lancet. If a case seems important but

remains challenging to fit it into a traditional case report for-
mat, it may be appropriate for a reflections piece. Many gen-
eralist and specialty journals, in addition to those noted
above, provide a venue for reflective pieces based on impor-
tant interactions with patients, although these are not strictly
considered case reports for the purposes of this book.
A useful article Writing and publishing case reports the
road to success provides ten categories of case reports [6]:
Totally original condition/new disease
Rare and previously sparsely reported condition
Unusual presentation of a common disease
Unexpected association between two relatively uncom-
mon symptoms/signs
Impact of one disease process on another
Unexpected event in the course of observing or treating a
patient
Impact of a treatment regime of one condition on another
disease
Unexpected complication of treatment or procedure
New and unique treatment
Honest mistakes in management
These criteria are helpful to look through when consider-
ing the suitability of a case for publication. A new theme from
this list is the concept of reporting mistakes (in contrast to
simply adverse events). Of course, before submitting such a
manuscript, the author should discuss the situation with insti-
tutional risk management representatives.
Another method to assess your case is to consider whether
its publication would make a positive contribution to medical
science. Five potential contributions of case reports include [7]:
Recognition and description of a new disease
Recognition of rare manifestations of a known disease
Elucidation of the mechanisms of a disease
Detection of adverse or beneficial side effects of drugs
(and other treatments)
Medical education and audit
A Process to Assess Your Case 47
While the lists outlined above can serve as a useful frame-

work for approaching a case report project, using a strictly
mechanistic approach may result in many important cases
not being submitted for publication. A review of ten recent
issues of the Journal of General Internal Medicine (JGIM) is
informative in this regard. Six clinical vignettes were pub-
lished in these ten issues, including a novel manifestation of a
rare disease (Campylobacter-Associated Hemolytic Uremic
Syndrome Associated with Pulmonary-Renal Syndrome [8]),
an unusual manifestation of a relatively uncommon problem
(Elevated Lactate Secondary to Gastrointestinal Beriberi
[9]), a somewhat novel treatment for a common problem
(Oral Rehydration Therapy and Feeding Replaces Total
Parenteral Nutrition: A Clinical Vignette [10]), a rare syn-
drome (An Unusual Case of Statin-Induced Myopathy: Anti-
HMGCoA Necrotizing Autoimmune Myopathy [11]), and
two more common diagnoses (Narcolepsy with Cataplexy in
an Elderly Woman [12] and A Case of Subacute Ataxia in the
Summertime: Tick Paralysis [13]). Strictly adhering to any of
the case-suitability guidance above may have resulted in
these well-written and very educational articles not being
published.
A Process to Assess Your Case

Building from the lists and criteria described above, we sug-
gest that aspiring authors ask themselves a series of questions
about their case to determine suitability for publication [14].
After giving many talks on this topic to faculty and house
staff, we have developed a modified five-question algorithm
to assess the suitability of a case for publication, which we
offer here:
1. Is there a diagnosis?
We previously believed that having a diagnosis was manda-
tory for a case report to be published. But, keep in mind
that there are over a million published case reports [15] and
over 60,000 are added every year [16]. There is very little
that is mandatory for publication, and even the axiom

there must be a diagnosis, is flexible. For example, a recent
case report entitled A possible new multiple endocrine
neoplasia mutation described a patient with concurrent
primary hyperparathyroidism, papillary thyroid cancer,
acromegaly, and renal cell carcinoma who tested negative
for MEN-1 and MEN-4 mutations. Despite the title, a new
mutation was not in fact identified: the lack of a diagnosis in
essence became the diagnosis. The authors accurately and
precisely stated, the currently reported case likely repre-
sents a unique and novel variant of MEN-1 or -4, [17] but
did not definitively make the diagnosis.
Nonetheless, case reports are certainly more publish-
able if there is a diagnosis. If a diagnosis is lacking, the
authors must be exceptionally rigorous, thorough, and
comprehensive so that reviewers do not read the manu-
script and say If only they had done the ________ test,
they would have made the diagnosis of ___________. In
addition, most reviewers and readers do not want to read a
case and learn at the end that the diagnosis remains
unknown. Rather, it is preferable to describe the case as a
new or variant syndrome that does not meet strict diagnos-
tic criteria.
2. Is the topic something strange, rare, or an uncommon pre-

sentation of a common problem?
This question captures the majority of case reports and
usually is the reason why a case has caught the physicians
eye in the first place. The literature is full of case reports of
rare syndromes or rare manifestations of syndromes. These
case reports may form the basis for larger case series and
even future scientific inquiry.
3. If it is not strange or rare, is it an important clinical issue?

High-impact clinical issues are often worthy of publica-
tion, even if the syndrome is not particularly rare. For
example, Early repolarization masquerading as STEMI
[18] is an important topic that merits consideration for
publication even if the described case scenario is not par-
ticularly rare.
Conclusion 49
4. Is there a diagnostic, therapeutic, or management dilemma?

If the answer to this question is yes, AND the case is
either rare or important, then it is very likely that the case
is suitable for publication. These cases may even be appro-
priate for publication as a clinical problem-solving (CPS)
exercise (see Chap. 10).
5. Is there an important teaching point?

Many cases do not quite meet the criteria described
above, yet still seem interesting enough to consider pub-
lishing. Oftentimes, this is because the punch line is
thought-provoking, poignant, or makes a critical teaching
point. The paper, Loss of the guide wire: a case report
[19] illustrates this point. For many physicians who place
central venous lines, remembering to hold onto the guide-
wire is an ordinary part of process. But those who read
this case report, which describes the consequences of not
always holding on to the wire (the lost guide wire was
seen extending from the saphenous vein through the vena
cava, right atrium, right ventricle, pulmonary artery and
lung tissue to the back of the neck) will surely never
loosen their grip on the wire. By highlighting the teaching
point that The operator must hold onto the guide wire at
all times, the authors made an otherwise straightfor-
ward case important and publishable.
Conclusion
The general publication criteria described above give an

overview of how many journals assess the publication
value of a case. Use the five-step process to more specifi-
cally evaluate the suitability of proceeding with writing a
case report. One of the best ways to corroborate conclu-
sions drawn from this process is to describe the case to
three or four colleagues. Would they read a report of the
case? Do they think it is interesting? Is there something
they learned from even the brief description of the case? If
the consensus is that the case is interesting enough to

report, there is very likely going to be an audience and
venue in which to publish it.
References
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testinal beriberi. J Gen Intern Med. 2016;31(1):1336.
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vignette. J Gen Intern Med. 2016;31(2):2557.
11. Nichols L, Pfeifer K, Mammen AL, Shahnoor N, Konersman
CG. An unusual case of statin-induced myopathy: anti-HMGCoA
necrotizing autoimmune myopathy. J Gen Intern Med.
2015;30(12):187983.
12. Suzuki S, Uehara T, Ohira Y, Ikusaka M. Narcolepsy with
cataplexy in an elderly woman. J Gen Intern Med. 2015;30(8):
12224.
13. Laufer CB, Chiota-McCollum N. A case of subacute ataxia in the
summertime: tick paralysis. J Gen Intern Med. 2015;30(8):
12257.
References 51
14. Mookherjee S, Berger G. Case reports: a how to guide for

attendings. SGIM Forum. 2015;38(6):89.
15. Rosselli D, Otero A. The case report is far from dead. Lancet.
2002;359(9300):84.
16. Sun GH, Aliu O, Hayward RA. Open-access electronic case
report journals: the rationale for case report guidelines. J Clin
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17. Buzzola R, Kurukulasuriya LR, Touza M, Litofsky NS, Brietzke
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Circ J. 2006;70(11):15202.
Chapter 6
How to Get Started
Introduction
Think about how many times you, a colleague or trainee have
said We should write this case up! Now consider how many
of these cases actually made it to publication. For many
authors, there is a gap in the degree of enthusiasm for an
interesting case and channeling that energy into submitting a
manuscript. This chapter describes four early steps for case
preparation and writing that will increase the likelihood of
publication. Table 6.1 outlines these key steps.
Obtain Consent
From the Hippocratic Oath: And whatsoever I shall see or hear
in the course of my profession, as well as outside my profession in
my intercourse with men, if it be what should not be published
abroad, I will never divulge, holding such things to be holy
secrets. [1]
Whether or not patient consent is required to publish a case

report is a source of confusion. Experienced authors will often
dismiss the need for consent, while others insist that consent is
mandatory even to submit a clinical vignette abstract to a con-
ference. The confusion is so pervasive that some authors will
actually try to submit a case report to a journal even when the
patient has refused to give consent [2]. Most authors accept

DOI 10.1007/978-3-319-41899-5_6
54 Chapter 6. How to Get Started
Table 6.1 Key steps to 1. Get consent always get consent!

get a case report started
2. Collect images and data early
3. Create a team
4. Just write something!
that they should not try to publish a case if the patient has
asked them to not do so; a more common scenario is one
where authors try to publish a case report when they do not
believe that consent is needed. For example, a case report
describing an ethical dilemma around the care of a child was
submitted to the British Medical Journal (BMJ); it was rejected
by the journal due to the lack of informed consent from the
patients parents [3]. The authors subsequently submitted the
manuscript to a second journal, where it was published [4]. In
a unique published discussion of their positions on the issue,
the editors of each journal provided their perspective:
The British Medical Journals position: Confidentiality is not an
absolute value, and both the common law and the General
Medical Council [the United Kingdoms standard setting organi-
zation for physicians] recognize that it can be breached without
consent when the public interest is sufficiently engaged. There is,
however, a high threshold for such disclosuressuch as preven-
tion of serious harm to an individual. Although there is clearly a
degree of public interest in the issues raised by Isaacs and col-
leagues case study, it is difficult to see how they begin to reach
such a threshold. [5]
The Journal of Paediatrics and Child Healths position: In this

instance we accepted the argument that seeking parental permis-
sion would have further compromised a difficult relationship with
the childs parents, making it even less likely to achieve an appro-
priate resolution to a challenging clinical and ethical situation. In
addition to the specific clinical and ethical issues generated by the
management of this case, the case study also raised important
ethical issues [6]
As this example illustrates, the question of foregoing

informed consent hinges on whether the content of the case
report is so important for the health of the public that an
internationally accepted respect for confidentiality and
Obtain Consent 55
consent may be superseded. This is a very high bar for most

case reports, and in practice it would be extraordinarily rare
to argue that publishing a single case report is necessary for
the good of the society as a whole.
The International Committee of Medical Journal
Editors (ICMJE) statement on patient privacy provides
further guidance on the issue of consent (Table 6.2).
Reviewing these guidelines raises several practical issues
for authors of case reports. First, precisely what entails
identifying information? Case reports include interesting,
often unusual details in a patients history. Depending on
these details and the circumstances of the case, the patient
could theoretically be identified by the reader. This is
especially true in the modern era, where many published
Table 6.2 International Committee of Medical Journal Editors

Protection of Privacy [7]
Patients have rights to privacy that should not be infringed
without informed consent.
Identifying information should not be published in written
descriptions, photographs, or pedigrees unless the information
is essential for scientific purposes and the patient (or parent or
guardian) gives written informed consent for publication.
Informed consent for this purpose requires that the patient
should be shown the manuscript to be published.
Identifying details should be omitted if they are not essential,
but patient data should never be altered or falsified in an
attempt to attain anonymity.
Complete anonymity is difficult to achieve, and informed
consent should be obtained if there is any doubt; for example,
masking of the eye region in photographs of patients is
inadequate protection of anonymity.
The requirement for informed consent should be included in
the journals instructions for authors.
When informed consent has been obtained, it should be
indicated in the published article.
case reports are accessible to the public, and technological

methods exist to aid in the identification of images, includ-
ing those that have ostensibly been de-identified [8].
Second, the ICMJE recommends that if informed consent
is obtained due to concern for the presence of identifying
information, the patient should be shown the manuscript
prior to publication. This may prove to be impractical in
many cases and impossible in others.
The ICMJE recommends that journals include informed
consent requirements in the author instructions. A 2004
review of case report instructions from 249 core journals
showed that only 29 specifically requested patient consent in
order to publish a case report [9]. Among journals that do
provide authors instructions on obtaining consent for case
reports, there is variability in what is required and under
what circumstances. While some have called for a universal
patient consent that will allow publication of case reports in
all medical journals [10], such a form does not currently
exist. Therefore, to maximize the number of journals to
which a case report may be submitted, it is logical at the
outset to follow the consent requirements of journals with
the most conservative requirements. BMJ Case Reports
author instructions are a useful resource in this regard
(Box 6.1).
The bottom line regarding consent for case reports:
Always obtain signed consent from patients!
Locate institution-specific consent forms usually these
are located in a forms repository, typically online.
Be sure to obtain consent for any images that you are even
considering using it is easy to decide later not to use the
images, but you will not be able to use them at all without
prior consent.
Look at the author instructions for five journals where you
might submit an eventual manuscript.
Determine if there are journal-specific consent forms that
need to be filled out.
Obtain Consent 57
Explain the process of manuscript submission and review

to the patient; ask them to sign any required consent forms
for all five of the likely target journals.
Keep a copy of each of these forms, and put another copy
in the patients medical record.
If identifiable information will be used in the case report,
in addition to obtaining consent for publication, remember
to ask the patient to review the manuscript prior to sub-
mission. Acquire multiple ways of contacting the patient
many months usually pass before the manuscript is
submitted, and patients can become difficult to contact.
Box 6.1 Consent Requirements from BMJ Case Reports [11]

Publication of any personal information about an
identifiable living patient requires the explicit consent
of the patient or guardian. This is a requirement under
the UKs Data Protection legislation. We expect authors
to use the BMJ consent form which is available in sev-
eral languages. You must have signed informed consent
from patients (or relatives/guardians) before submitting
to BMJ Case Reports. Please anonymise the patients
details as much as possible, eg, specific ages, ethnicity,
occupations. For living patients this is a legal require-
ment and we will not send your article for review with-
out explicit consent from the patient or guardian. If the
patient is dead the Data Protection Act does not apply,
but the authors must seek permission from a relative
(ideally the next of kin). If you dont have signed con-
sent from a deceased patient, guardian or family, the
head of your medical team/hospital or legal team must
take responsibility that exhaustive attempts have been
made to contact the family and that the paper has been
sufficiently anonymised not to cause harm to the
patient or their family. You will need to upload a signed
document to this effect.
Collect Images and Data Early

The best case reports include images to enhance the clinical
story and highlight teaching points. Authors should attempt
to acquire these images as soon as they consider writing a
case report (after obtaining patient consent).
Consider what images will add value to the report:
Take multiple photographs to document specific findings
while you still have easy access to the patient (either in the
inpatient setting or in an outpatient clinic).
Place a ruler near the image if it will be beneficial to dem-
onstrate the size of the findings.
Document before and after images that enhance teach-
ing points, such as before and after an examination maneu-
ver, or before and after a treatment modality.
Do not forget about paper-only studies or results:
While in Western countries most medical records are elec-
tronic, some study results may only be accessible in the
paper records. These paper records can be difficult to
obtain once the patient has left the hospital. For example,
at our institution, nocturnal oximetry reports were placed
in the paper record and disappeared into an off-site
medical record storage facility once the patient was
discharged.
As you are considering a case report, take photographs or
make copies of any paper records which will be accessible
for a limited time.
Capture other images early:
Pathologic, radiographic, and hematologic images are also
best captured while the patient is still being cared for by
the team planning to write the case report.
You may need the assistance of specialists to select the
best images; these collaborators take more initiative if the
patient is still under their care.
Create a Team 59
In contrast, approaching the pathology lab months after a

discharge to help locate and photograph the right slides
can be much more difficult.
Think creatively about obtaining other images:
What will be the most impactful and educational for your
particular case?
If the patient is going to the operating room, ask the
surgical team to take photographs and share them, if
possible.
If the patient is scheduled for a unique study that will help
make the diagnosis, try photographing the patient during
the study itself (in addition to obtaining the diagnostic
images).
Consider photographing interesting findings that are
external to the patient for example, a test tube of lipemic
blood or unusual appearing bodily fluids.
Create a Team
Once you have identified an appropriate case (see Chap. 5),
obtained consent, and collected images and data, the next
step is to create the authorship team. This can be problematic,
especially when multiple specialists and subspecialists are
involved in caring for the patient. It is critical to be precise
and transparent about the roles and expected authorship. Be
prepared to step aside to let another team take the lead on
writing up a case if they played a larger role in the patients
care. Conversely, if you take the lead in a case where others
have stepped aside, it is important to quickly follow through
on writing the manuscript rather than delaying it for some
unknown time in the future. As you select team members,
keep in mind that many journals have strict limits on the
number of authors for case reports (often no more than four),
and many further limit the number of authors for clinical
images reports.
Table 6.3 Case report authorship responsibilities

First author Middle author(s) Last/senior author
Obtain consent Perform Verify appropriate
Obtain images aspects of consent was obtained
Complete literature Advise on the selection
literature review review and use of images to
Write the first Help obtain illustrate teaching
draft of the consent and points
manuscript images, if Verify literature review
Ensure deadlines needed Extensively edit
are met Edit manuscript for content,
Submit manuscript manuscript flow, and clarity
to journal Fast turn Adhere to deadlines
Respond to around Advise on the
reviewers submission process
Assist first author
respond to reviewers
ICMJE authorship criteria for all authors; all criteria must
be met [12]
1. Substantial contributions to the conception or design of the
work; or the acquisition, analysis, or interpretation of data for
the work
2. Drafting the work or revising it critically for important
intellectual content
3. Final approval of the version to be published
4. Agreement to be accountable for all aspects of the work in
ensuring that questions related to the accuracy or integrity of
any part of the work are appropriately investigated and
resolved
Table 6.3 outlines standard case report authorship respon-

sibilities. Clearly establish roles and authorship by writing
down exactly what you propose for the team. Note that while
middle authors have considerably fewer tasks (appropriately
for their middle author status) than first and last authors, they
must agree to quickly turn around the manuscript with edits
and comments when asked. If roles and responsibilities were
previously discussed with potential co-authors, send a
follow-up e-mail delineating what was agreed upon to ensure
Just Write Something! 61
Table 6.4 Example e-mail to establish authorship and responsibilities
Dear Dr. _________,
It was a pleasure taking care of Mr. _______ alongside you earlier this month.
As we discussed, it would be great to publish this as a case report.
I propose that I will take the lead as the first author for this paper. I will obtain consent
and obtain the images that we discussed. I will complete a literature review and write the
first draft in its entirety by May 1st.
I propose that you will be the senior (last) author. If you agree to this, you will verify the
completeness of my literature review, review and edit my draft by June 1st, and help with
any responses needed to reviewer comments.
I suggest that we invite Dr. ________ to be a middle author on this project.

Given her expertise, I will ask her to pay particular attention to the novel treatment that
will be described in this paper. I will ask her to commit to editing and returning the
manuscript to me by June 15th.
Please let me know if you are in agreement with this plan. I look forward to working on
this with you!
Best regards,
Dr. __________
Adapted from Mookherjee and Berger [13]
that everyone shares the same expectations (Table 6.4). See

Chap. 10 for more on authorship responsibilities, with an
emphasis on clinical problem-solving manuscripts.
Just Write Something!

After deciding to turn the case into a case report, spend a few
hours reviewing the literature to verify how many prior
reports there have been on the topic. Use the references from
more recent case reports to quickly identify prior publica-
tions germane to the case. Some of the older publications
may be otherwise difficult to find using online databases. For
most forms of case reports, it is expected (but not always
mandatory) to state how many times the syndrome, condi-
tion, or finding has been previously reported.
Now, it is time to conquer the inertia Chaps. 7, 8, 9, and
10 provide detailed guidance on the format and content of
different types of case reports. Refer to those guidelines and
simply start writing! Write with the knowledge that whatever

is created will inevitably undergo extensive editing. Write
without regard to style or voice this can be polished later
(see Chap. 12 for manuscript polishing tips). Simply write
something this is the only way to get the project started!
Conclusion
While thousands of case reports are published every year,
thousands more are not, due to lack of knowledge and expe-
rience in the mechanics of publishing a case. This chapter
provides a brief and practical framework to help get a case
report started. Pay particular attention to obtaining consent
many case reports have perished due to lack of appropriate
consent being obtained in a timely fashion. Remember what
draws the eye when reading a case report an evocative
image enhances any report. Purposefully create a team and
be explicit regarding roles and responsibilities. Finally, just
write something!
References
1. Thompson IE. The nature of confidentiality. J Med Ethics.
1979;5(2):5764.
2. Nussmeier N, Saidman LJ, Shafer S. A&A case reports: a prog-
ress report and an update on requirements for patient consent.
Anesth Analg. 2014;119(6):1251.
3. Isaacs D, Kilham HA, Jacobe S, Ryan MM, Tobin B. Gaining
consent for publication in difficult cases involving children. BMJ.
2008;337:a1231.
4. Ryan MM, Kilham H, Jacobe S, Tobin B, Isaacs D. Spinal muscu-
lar atrophy type 1: is long-term mechanical ventilation ethical?
J Paediatr Child Health. 2007;43(4):23742.
5. Newson AJ, Sheather J. Commentary: consent and confidential-
ity in publishingthe view of the BMJs ethics committee. BMJ.
2008;337:a1232.
6. Oberklaid F. Commentary: consent to publicationno absolutes.
BMJ. 2008;337:a1233.
References 63
7. Editors ICoMJ. Protection of patients rights to privacy. BMJ.

1995;311(7015):1272.
8. Gibson E. Publication of case reports: is consent required?
Paediatr Child Health. 2008;13(8):6667.
9. Sorinola O, Olufowobi O, Coomarasamy A, Khan KS. Instructions
to authors for case reporting are limited: a review of a core jour-
nal list. BMC Med Educ. 2004;4:4.
10. Aldridge RW. Simplifying consent for publication of case
reports. BMJ. 2008;337:a1878.
11. BMJ Case Reports: Instructions for authors. Available from:
http://casereports.bmj.com/site/about/guidelines.xhtml.
12. Guidelines on authorship. International Committee of Medical
Journal Editors. Br Med J (Clin Res Ed). 1985;291(6497):722.
13. Mookherjee S, Berger G. Case reports: a how to guide for
attendings. SGIM Forum. 2015;38(6):89.
Chapter 7
How to Write a Traditional
Case Report
Clifford D. Packer
The Title
There are two schools of thought on case report titles.
Some authors favor the cute or clever title, which can be
humorous, mysterious, or (in the worst-case scenario) a
play on words or a pun. The clever or humorous title may
be good fun, but it has several drawbacks. It makes the
case report obscure, a riddle that most readers will not
bother to solve by reading it. It is also less searchable than
a straightforward title, which provides the gist of the case
at a glance. There is evidence, in fact, that scientific journal
articles with amusing titles are cited less than comparable
articles with straightforward titles [1]. In my own practice,
I once had a patient with a puzzling case of hypokalemia,
whom I eventually discovered to be drinking 4 l of cola per
day. When I wrote the case report, humorous titles such as
hypokalemia on ice or a fizzy mystery did occur to me,
but common sense prevailed and I titled it Chronic
hypokalemia due to excessive cola consumption: a case
report [2].
The best strategy is to describe in the title what is of the
greatest interest to the author, the crux of the case, in the
plainest possible terms. In other words, as Milos Jenicek
has put it, the title should always get right to the point

DOI 10.1007/978-3-319-41899-5_7
66 Chapter 7. How to Write a Traditional Case Report
[3]. One of my first case reports was about a young violin-

ist who became unable to control and vary his vibrato
when he was started on atenolol for treatment of hyper-
tension. My too-general title was Beta-blockers, stage
fright, and vibrato: a case report [4]. A better title would
have been Impairment of violinists vibrato caused by
chronic atenolol treatment: a case report. Since then, I
have been careful to make my titles as specific as possible.
When I had a patient with three autoimmune diseases at
the same time, my title was Concurrent reactive arthritis,
Graves disease, and warm autoimmune hemolytic anemia:
a case report [5]. When another patient came in with a
lymphoma-like presentation of vertebral sarcoidosis 16
years after his primary sarcoidosis had resolved, our title
was Vertebral sarcoidosis mimicking lytic osseous metas-
tases: development 16 years after apparent resolution of
thoracic sarcoidosis [6]. The primary teaching point that
quiescent sarcoidosis can recrudesce many years later in
the form of vertebral bone lesions is clearly spelled out in
the title.
Some authors recommend that the words case report,
case study, or case series be included in the title [7, 8].
This is useful, both to categorize the paper for indexing pur-
poses and to inform the prospective reader about the type
of content and evidence that is presented. The author
should feel free to use a case report and review of the lit-
erature if a thorough literature review is included. Other
variations are also acceptable: one case report in which we
presented a long discussion of the mechanisms of disease
for a patient with intractable vomiting was titled
Cannabinoid hyperemesis syndrome: a case report and
review of pathophysiology [9].
The title, then, should be a clear and specific description
of the main point of the case, not a riddle wrapped in a
mystery inside an enigma. We should reserve the creative
titles for case reports formatted as clinical quizzes or clini-
cal problem-solving cases, which will be discussed in Chaps.
8 and 10.
The Abstract 67
The Abstract
The abstract is nothing more or less than a brief prcis of a

case report. It may be structured or unstructured, and gener-
ally runs from 150 to 300 words. Because it is freely available
on the electronic database, the quality of the abstract often
determines whether or not researchers will go on to view the
full case report, cite it, or use it for patient care. Therefore, the
abstract must be a short, well-organized, and readable sum-
mary that touches on all the major points of the case.
Typically, whether structured or unstructured, the case report
abstract has three sections: Introduction, Case Presentation,
and Conclusion. The Introduction gives the background for
the case report, the context of the case in the literature (i.e.,
this is the third case, the only case, etc.), and the ratio-
nale for publishing it. The Case Presentation is a succinct
summary of the case that includes the age and gender of the
patient, key history and physical exam findings, lab testing,
imaging, and highlights of the clinical course including
response to treatment. The Conclusion describes the clinical
impact of the case and gives the important lesson or teaching
point. Consider the following two abstracts, where the first is
unstructured and the second is structured:
Vertebral sarcoidosis is a rare condition that can present with
persistent back pain, often with concurrent lung, lymph node, or
skin involvement. It can produce lytic or blastic osseous lesions
that are indistinguishable from metastatic cancer on bone scan
and magnetic resonance imaging (MRI). It usually occurs at the
time of initial diagnosis of sarcoidosis, but may in very rare cases
appear many years after presumed resolution of thoracic sarcoid-
osis. We present the case of a 47-year-old man who developed
persistent low back pain 16 years after spontaneous resolution of
stage I pulmonary sarcoidosis. MRI of the spine showed lytic
thoracic and lumbar vertebral lesions. Computed tomography of
the chest showed a pleural-based lung mass, multiple pulmonary
nodules, and hilar and mediastinal lymphadenopathy. Positron
emission tomography with fluorodeoxyglucose was widely posi-
tive, including at the vertebral foci noted on MRI. Metastatic
lymphoma was suspected, but mediastinal lymph node and
vertebral body biopsies showed noncaseating granulomas with

negative stains for acid-fast bacilli and fungi. After 1 month of
treatment with prednisone, the angiotensin-converting enzyme
level and erythrocyte sedimentation rate had normalized, and the
back pain was substantially improved. We found only 1 case
report of a longer interval between resolution of initial sarcoid-
osis and development of vertebral involvement [6].
INTRODUCTION: Metformin is a widely prescribed biguanide

antidiabetic drug that has been implicated as a cause of hemolytic
anemia in three previous case reports. We report a case of rapidly
fatal hemolysis that was temporally associated with the initiation of
metformin treatment for diabetes. Clinicians need to be aware of
this rare but potentially serious side effect of metformin.
CASE PRESENTATION: A 56-year-old Caucasian man with
type 2 diabetes mellitus was started on metformin to improve
glycemic control. Shortly afterwards, he developed progressive
fatigue, exertional dyspnea, cranberry-colored urine and jaundice.
Laboratory studies showed severe hemolysis, with a drop in
hemoglobin from 14.7 to 6.6 g/dl over 4 days, markedly elevated
lactate dehydrogenase, bilirubin and reticulocyte counts, and a
low haptoglobin level. A peripheral blood smear showed no schis-
tocytes, and a direct Coombs test was positive for anti-IgG and
negative for anti-C3. Despite corticosteroid treatment and trans-
fusion of packed red blood cells, the patient developed increasing
dyspnea, hypotension, further decline in hemoglobin to 3.3 g/dl,
and fatal cardiorespiratory arrest 12 hours after admission.
CONCLUSION: The serologic findings in this case suggest an
autoimmune hemolytic anemia, caused either by a drug-induced
autoantibody or a warm autoantibody. Based on the temporal
association with metformin and the lack of other clear precipitat-
ing causes, we propose that metformin-induced hemolysis with a
drug-induced autoantibody is a strong possibility. This mechanism
differs from a previously described case with a possible antibody
to the erythrocyte-drug complex. It has been shown, however,
that hemolysis may occur via multiple mechanisms from the same
drug. Clinicians should consider the possibility of metformin-
associated immune hemolytic anemia in patients with otherwise
unexplained hemolysis [10].
In the unstructured abstract, we learn that vertebral sar-

coidosis is rare, that it can mimic metastatic cancer, and that
it may occur many years after apparent resolution of the ini-
tial episode of sarcoidosis. The structured abstract puts the
The Introduction 69
case in context three previous cases, this is the first report

of a fatality gives key symptoms and laboratory findings,
summarizes a hypothesis on the mechanism of metformin-
induced hemolysis, and finishes with the teaching point that
metformin should be considered in patients with otherwise
unexplained hemolysis. Both abstracts cover background,
clinical context, key findings, and teaching points.
The abstract should be written last, since it is much easier
to write a summary of a finished manuscript. Remember that
the abstract should not contain any new information that is
not presented in the body of the case report; it is strictly a
summary. It should not act as an introduction to the paper, or
include any citations.
The Introduction
This section should briefly summarize the background and
context of the case report. If the case involves an unusual
presentation or natural history of a disease, the usual course
of the disease should be described; if the case is a new dis-
ease or syndrome, this should be clearly stated. If it is an
adverse drug reaction, the properties and common uses of
the drug and previous reports of side effects should be men-
tioned. If the case report presents a new surgical technique,
the standard technique should be described. The introduc-
tion should also include a brief literature review which puts
the case in its clinical context. For example, if five other
authors have described a similar clinical presentation, or if
there are three previous reports of a similar side effect, or if
one other surgeon has tried the new approach, these should
be cited and mentioned briefly in the introduction. (Typically,
the details of previous case reports and comparisons with the
present case are reserved for the Discussion.) The introduc-
tion should end with a very brief statement, usually one
sentence, of what is being reported in the article, beginning
with a phrase such as in this case, we report, or we
describe.
In the introduction, brevity is important. The aim is to ori-

ent the reader to the context without getting bogged down in
the fine details, which will come later. In the following exam-
ple, the context and purpose of an adverse drug reaction case
are given in four sentences:
Romiplostim is a thrombopoietin (TPO) mimetic (median half-
life = 3.5 days) currently considered a second-line treatment for
idiopathic thrombocytopenic purpura (ITP). Clinical trials have
demonstrated efficacy in increasing long-term platelet counts. In
a few case reports, romiplostim has been used as an effective
bridge to splenectomy. We describe a patient with refractory ITP
who developed severe postsplenectomy rebound thrombocytope-
nia that occurred when a single romiplostim dose was held at the
time of surgery [11].
Here is an even briefer Introduction that gets the job done

in three sentences:
There are 4 published case reports of severe chronic hypokalemia
due to long-term, excessive cola consumption. Complications
described in the reports include hypokalemic myopathy, hypoka-
lemic nephropathy, and nephrogenic diabetes insipidus. In this
case, a patient developed severe chronic hypokalemia and prob-
able hypokalemic myopathy due to consumption of 4 liters of
Pepsi-Cola per day [2].
Other examples of effective and succinct introductions:

Patients with chronic lithium toxicity typically present with symp-
toms of agitation, confusion, tremor, ataxia, and hyperreflexia. In
rare cases, however, lithium toxicity can present with transient
cognitive and language deficits. We report the case of a lithium-
toxic patient who presented with transient transcortical motor
aphasia, which resolved 2 days after discontinuation of lithium.
This is the first report of focal transcortical motor aphasia in a
patient with lithium toxicity [12].
Metformin, a biguanide antidiabetic drug, has been implicated

as a cause of lactic acidosis, usually in a setting of renal failure, IV
contrast administration, shock, sepsis, hypoxemia, or liver disease.
Although metformin can cause mild lactic acidemia in type 2
diabetes mellitus patients with normal renal function, there are
very few case reports of lactic acidosis in patients with normal
renal function and no other obvious precipitating cause. In the
following case, a metformin-treated man with mild and limited
The Case Description 71
stroke symptoms and normal renal function developed lactic aci-

dosis in the absence of other risk factors [13].
Spigelian hernias are rare and often challenging to diagnose.

Although many case reports have described the presence of a
variety of abdominal organs found in Spigelian hernias, there are
no reports of an incarcerated appendix repaired laparoscopically.
The use of laparoscopic technique in this case provided easy iden-
tification of the incarcerated structure and allowed us to perform
an appendectomy without a large incision and with minimal dis-
section of the abdominal wall [14].
The Case Description

The biggest mistake my students make when writing up their
case reports is putting too much information into their case
descriptions. This is understandable, since they are in the
habit of presenting their cases comprehensively on the wards.
The key to a good case description is focus: include only the
parts of the history, physical exam, lab and imaging results,
and clinical course that pertain directly to the case report
topic. For example, in a patient with hemolysis, the presence
or absence of scleral icterus, light stools, dark urine, abdomi-
nal pain, fever, and hepatosplenomegaly should be noted;
pertinent medications and relevant family, social, and travel
histories should be included; and lab results should include
the CBC, reticulocyte count, bilirubin, LDH, haptoglobin,
G6PD level, peripheral smear, and Coombs test. There
should also be a clear timeline for the clinical and laboratory
findings, both in the text and in tables or graphs as needed.
Other data, such as the patients chronic eczema, mild COPD,
recurrent UTIs, and chronic back pain, should not be
included unless directly relevant to the case (e.g., if the
patient recently started a sulfa antibiotic for a UTI). The
course, diagnostic work-up, and treatment of the hemolysis
should be central. Unrelated complications and events should
be left out.
The concept of clinimetrics is very important to consider
in the case description [3]. Clinimetrics is concerned with the
accurate measurement of clinical data, and includes patient

demographics, clinical biomarkers such as physical
examination maneuvers (many of which have well-estab-
lished odds ratios), laboratory tests, and reproducible indices
such as TNM cancer staging, the Glasgow Coma Scale, the
Duke criteria for endocarditis, or the Naranjo Adverse Drug
Reaction Probability Scale. Careful adherence to clinimetric
principles improves the evidence value of a case report and
makes it more useful for clinical decision-making. The case
presentation should include all relevant clinical biomarkers
and scores for any applicable probability scales or other indi-
ces. For example, any case report of endocarditis must include
information on blood culture results, presence or absence of
a new regurgitant murmur, echocardiogram findings, and the
presence of immunologic or vascular phenomena. From these
data, a Duke criteria score should be given. Without these
data, the case report will be neither useful nor publishable.
Therefore, the author must take the time to research all per-
tinent clinical biomarkers and diagnostic criteria before writ-
ing the case description.
Table 7.1 lists the essential elements of the case descrip-
tion. All elements should be included whenever possible.
Rarely, a case report might be purely descriptive, with no
therapeutic intervention, or the clinical outcome might be
Table 7.1 Essential elements of the case description

1. Patient demographics: age, gender, and race
2. Pertinent history, physical exam, laboratory, and imaging
findings
3. Timeline of important clinical events (both in text and graph
or table form)
4. Diagnostic assessment, including applicable biomarkers,
indices, and rating scales
5. Therapeutic interventions
6. Clinical outcome of case
The Case Description 73
uncertain. However, case reports that lack one or more of

these elements, even if intriguing, are rarely publishable.
Consider the following example of a case description with
all essential elements. The first paragraph gives the patient
demographics, focused history, and a timeline (Fig. 7.1) with
hospitalizations and serum potassium values over a 21-month
period. The timeline reveals that the hypokalemia resolved
during the three hospitalizations, then recurred each time
after discharge. Note that all prescribed medications are
listed, because it is important that the patient was not taking
any medications likely to cause hypokalemia, and that he was
taking a potassium supplement:
A 52-year-old white male with O2-dependent COPD, hyperten-
sion, GERD, idiopathic gastroparesis, and chronic low back pain
was noted to have persistent hypokalemia in the 2.73.3 meq/L
range over more than 2 years. He complained also of chronic
generalized weakness and fatigue. He denied nausea or vomiting,
but did have occasional loose stools. The hypokalemia persisted
despite discontinuation of diuretic treatment for hypertension
and fludrocortisone that had been prescribed briefly for ortho-
static hypotension. There was no improvement with aggressive
oral potassium supplementation in amounts up to 120 meq per
day. The patient's serum potassium level normalized on three
Potassium (Serum) Ref Low 3.7 Ref High 5
4
meq/L
8/1/2006 11/1/2006 2/1/2007 5/1/2007 8/1/2007 11/1/2007 2/1/2008 5/1/2008
Figure 7.1 Serum potassium values from July 2006 to May 2008.
Note normalization of serum potassium levels during hospitaliza-
tions in 7/06, 1/07, and 7/07. Also note improvement in potassium
level from 3.0 to 3.5 mg/dL between 5/1/08 and 5/16/08, when the
patient decreased his cola consumption from 4 to 2 l per day
(Reproduced with permission from Packer [2])
occasions when he was hospitalized and given supplemental

potassium (COPD exacerbations in 7/06 and 1/07, pseudoseizures
in 7/07), but the hypokalemia promptly recurred after discharge
from the hospital [Fig. 7.1]. His medications were paroxetine,
trazodone, pregabalin, sustained-release morphine, loratadine,
isosorbide mononitrate, lisinopril, metoprolol, simvastatin,
omeprazole, metoclopramide, potassium chloride, calcium/vita-
min D tablets, alendronate, and mometasone, tiotropium, and
albuterol inhalers. He smoked one-half pack of cigarettes per day
and did not drink alcohol.
The second and third paragraphs give the physical examina-

tion findings and laboratory test results. The physical findings
indicate that the patient does not have signs of Cushings syn-
drome, a possible secondary cause of hypokalemia, and include
the mild generalized muscle weakness which could indicate
hypokalemic myopathy. Laboratory results include serum
aldosterone, plasma renin activity, and urine electrolytes, which
rule out primary hyperaldosteronism or other forms of renal
potassium wasting (in retrospect, a transtubular potassium
gradient would also have been useful but was not included):
On physical examination, he was a chronically ill-appearing man
wearing a nasal cannula. Height was 69 inches, weight 205 pounds.
There were no cushingoid facies, buffalo hump, or abdominal
striae. Vital signs were temperature 98.6 degrees, pulse 95, respi-
ratory rate 14, blood pressure 128/73. There was no thyromegaly
or lymphadenopathy. Lungs showed decreased breath sounds and
mild expiratory wheezes bilaterally. Heart sounds were regular
with no murmurs, rubs, or gallops. The abdomen was soft and non-
tender, with no masses or organomegaly. Extremities showed no
edema, clubbing or cyanosis. The neurologic examination revealed
mild generalized muscular weakness (4+/5) and normal deep
tendon reflexes.
Laboratory results include serum sodium 137 mg/dL, potas-
sium 3.0 mg/dL, chloride 95 mmol/L, CO2 30.0 mmol/L, blood
urea nitrogen 5 mg/dL, creatinine 0.8 mg/dL, calcium 9.3 mg/dL,
phosphorus 4.1 mg/dL, albumin 3.6 g/dL, ferritin 126 ng/mL,
hemoglobin 12.7 g/dL, white blood cell count 10.6 K/cmm, and
platelet count 160 K/cmm. Serum aldosterone was 4.8 ng/dL (nor-
mal 431 ng/dL) and the plasma renin activity was 0.33 ng/mL/hr
(normal 1.313.96 ng/mL/hr upright, 0.152.33 ng/mL/hr supine).
Spot urine potassium was 8.6 mEq/L, urine sodium was < 10
mEq/L, and urine chloride was 16 mmol/L [2].
The Timeline 75
Finally, the fourth paragraph gives the diagnostic assess-

ment and reveals the key dietary information which was
obtained at that point. The connection between excessive
cola consumption and hypokalemia is established. The clini-
cal outcome is the near-normalization of the potassium level
when the patient cut his cola consumption in half:
In the absence of a clear explanation for this patient's chronic

hypokalemia, he was asked to give the details of his diet. He
admitted to drinking 4 liters of Pepsi-Cola per day for the past
several years. It was his habit to sip cola slowly but almost con-
tinuously, throughout the day. When hospitalized, he had stopped
drinking cola and his potassium levels had temporarily normal-
ized. In early May 2008, he decreased his cola intake to 2 liters per
day, with a resultant increase in the serum potassium from 3.0 to
3.5 mg/dL (Fig. 7.1) [2].
Note that the case description does not discuss the differ-
ential diagnosis of the hypokalemia, but simply gives the tests
that were done to evaluate it. Also, the case description does
not include any information on possible mechanisms of cola-
induced hypokalemia. Differential diagnosis and mechanisms
of disease are reserved for the discussion.
The Timeline
The timeline is critical in case reports that involve changes in
clinical parameters over time, especially where inferences are
made about cause and effect. Timelines are much clearer than
long prose passages when it comes to telling the stories of
adverse drug reactions or other complex case histories. In
Fig. 7.1, the timeline clearly shows chronic hypokalemia with
normalization of potassium levels only during hospitaliza-
tions. Figure 7.2 is from a case report of a 91-year-old man
with thrombocytopenia in the setting of biocompatible dialy-
sis membranes, with daily platelet counts and arrows to indi-
cate the various dialyzer types that were used over a 3-week
period [15]. The graph gives conclusive evidence that platelet
counts dropped repeatedly when polysulfone membrane
76
250
200
Chapter 7.
150
100
Platelet count (K/cmm)

50
0
5 pm 6 am 6 am 6 am 1 pm 11 am 1 pm 6 am 6 am 6 am 6 am 6 am 6 am 6 am 11 am 6 am 9 pm 6 am 6 am 6 am
17-Nov 19-Nov 20-Nov 21-Nov 21-Nov 22-Nov 23-Nov 24-Nov 25-Nov 26-Nov 27-Nov 28-Nov 29-Nov 30-Nov 1-Dec 2-Dec 2-Dec 3-Dec 5-Dec 6-Dec
Figure 7.2 Demonstration of chronological platelet levels measured in this patient. Dashed arrows indicate adminis-
tration of hemodialysis using either Optiflux 200 or 18NR polysulfone membrane dialyzers (Fresenius). Solid arrows
indicate administration of hemodialysis using AM100 dialyzer with alkyl ether polymer-grafted cellulose membrane
How to Write a Traditional Case Report
(Reproduced with permission from Muir and Packer [15])

The Discussion 77
dialyzers were used, and then recovered when the patient was
switched to a cellulose membrane dialyzer. Timelines of this
kind can be very useful in demonstrating cause and effect,
especially in adverse drug reaction cases.
A simple clinical timeline is often used to show the natural
history of a disease process. Figure 7.3 is a timeline of events,
symptoms, and diagnosis in a case of human rabies. This was
the first report of rabies acquired in the United States, but
with symptom onset, medical management, and diagnosis
abroad [16]. The timeline includes all key events, from sus-
pected bat bite to postmortem analysis of brain tissue, and
gives important details on the patients travel history and the
rapid progression of symptoms over his last 5 weeks. A great
deal of data is neatly and concisely presented on this simple
timeline.
Although graphs are more visually effective as timelines,
tables can also be useful if there are multiple data points that
would lead to an overly cluttered graph. Consider Table 7.2,
which gives laboratory values from a case of metformin-
associated lactic acidosis in a patient with vertebral artery
dissection and essentially normal renal function [13]. The
table allows for a quick review of day-by-day changes in the
important laboratory values as the patients lactic acidosis
peaked and then resolved over the course of 4 days.
The timeline should be referenced and briefly described in
the case description. Any critical analysis of the timeline, such
as comment on the relatedness of events or the likelihood of
causal relationships, should be left to the discussion.
The Discussion
The aims of the discussion are simple: to put the case in con-
text, explain what happened, explore the implications, and
give a useful teaching point. Table 7.3 gives the essential ele-
ments of the discussion, with the specific steps needed to
fulfill these four key requirements. There is a logical flow
from context to explanation to speculation and the teaching
78
July 8
Iraq
Clinic 8: uncontrolled tremors,
sweating, anxiety, and malaise
Chapter 7.
July 9
UAE
June 1418 Comatose, untubated
California July 5
Asymptomatic Iraq August 22
Clinic A: arm Rabies diagnosis
shaking malaise confirmed by testing
June 11 June 25
Late March 2012 of brain tissue
Iraq Thailand
California
Infectious period begins Right arm and July 31
Suspected bat bite
shoulder pain, Switzerland
exhaustion Patient died; rabies
suspected
Jan Feb Mar Apr May Jun 5 10 15 20 25 Jul 5 10 15 20 25 Aug 5 10 15 20 25
Figure 7.3 Timeline of events, reported symptoms, and diagnosis in a case of human rabies in a US resident March
August 2012 (Reproduced with permission from MMWR Morb Mortal Wkly Rep [16])
The Discussion 79
Table 7.2 Laboratory values

20 days
before On
Variable admission admission Day 2 Day 3 Day 4
Lactate 5.2 4.9 2.6 0.9
(mEq/L)
CO2 27 17 22 26 22
(mmol/L)
Anion gap 11 21 15 10 14
BUN (mg/ 14 31 18 13 11
dL)
Creatinine 1.0 1.4 1.2 1.0 1.1
(mg/dL)
CPK (IU/L) 51
Adapted with permission from Wolters Kluwer Health [13]
From: Metformin-associated lactic acidosis in a patient with verte-
bral artery dissection
Table 7.3 Essential elements of the discussion

Context of the case
Review of relevant anatomy, physiology, pharmacology, etc.
Focused literature review
Comparison with other cases: what is new, unusual, or unique
about the case?
Explanation of events
Assessment of cause and effect or relatedness of events (refer
to the timeline as needed)
Evaluation of differential diagnosis and alternative explanations
Proposed explanation or hypothesis, with rationale
Critique of the evidence value of the case report (strengths and
weaknesses)
Critique of management of the case (optional)
Speculation
Broader implications of the case, possible future research
Teaching point
A brief, aphoristic, and memorable teaching point to conclude
the discussion
point explanation is meaningless without context, and the

teaching point is not credible without a clear and convincing
explanation of the case. Therefore, it is best to write the dis-
cussion in the order suggested in Table 7.3.
Context of the Case

Establishing the context usually begins with a brief review of
the clinical setting. For instance, in an adverse drug reaction
involving the cytochrome p450 system, factors leading to
enzyme inhibition should be discussed; in a case of a Spigelian
hernia, a brief summary of the etiology, anatomy, presenta-
tion, and surgical management of these rare hernias should
be offered. The next step is the literature review, which
should be as specific and focused as possible (see Chap. 5).
Use of an advanced search tool such as the MeSH database
in PubMed is highly recommended.
An excellent way to compare a group of cases is to make
a table (Table 7.4) with key demographic and clinical fea-
tures. Always include the current case (listed as this case or
this study) as the final entry on the table.
The accompanying discussion highlights the important dif-
ferences between the previous cases and the current case, and
proposes a mechanism to explain the differences in the
Direct Coombs (DAT) test results:
The possible mechanism of metformin-induced hemolytic anemia
discussed here is different from that proposed by Kashyap and
Kashyap in their report. Their patient's DAT was positive for
anti-C3 and negative for anti-IgG, which suggests the formation
of an antibody against the erythrocyte-drug complex. In contrast,
our patient's DAT was consistent with autoantibody formation.
This is not necessarily a contradiction, since it has been shown
that the same drug can cause many if not all of the mechanisms of
DIIHA. In fact, one mechanism may simply be more pronounced
and identifiable in a particular patient. Observations of DIIHA
caused by third-generation cephalosporins support the notion of
multiple mechanisms for the same drug [10].
This type of comparison table can accommodate an almost

unlimited number of cases and variables (Table 7.5).
Table 7.4 Reported cases of metformin-induced hemolytic anemia
Recurrence
Time from of
starting hemolysis
metformin with
Case Pt. age to onset of metformin
report (years) Gender symptoms Direct Coombs G6PD level rechallenge Outcome
Lin et al. 46 Male 10 days Equivocal Normal Yes Recovery
Kashyap 51 Female 9 days Positive (IgG, Normal Yes Recovery
and +C3)
Kashyap
Meir et al. 68 Female 14 days Negative Decreased N/A Recovery
Packer 56 Male 12 days Positive (+IgG, N/A N/A Death
et al. (this C3)
study)
Adapted with permission from Packer et al. [10]
Context of the Case
81
Table 7.5 Reported cases of acute obstructive suppurative pancreatic ductitis
82
AOSPD case reports

Patient Prior Relevant
Case age/ endoscopic comorbid Presenting CT scan ERCP Culture Clinical
report gender intervention conditions symptoms WBC results results results course
Weinman 74/ Biliary Chronic Abdominal 17.9 Dilated Pancreatic E. coli Resolved,
Chapter 7.
[1] male sphincterotomy pancreatitis, pain, fever, pancreatic duct stone doing
DM N/V duct with removed, well at 18
5 mm stone stented months
Tajima 73/ No Chronic Abdominal 14.2 Dilated Pancreatic N/A Resolved

et al. [2] male pancreatitis, pain, fever pancreatic stricture,
pancreatic duct, tumor stented
CA at head of
pancreas
Deeb 46/ ERCP, Chronic Abdominal N/A Dilated Pancreatic Klebsiella Resolved
et al. [3] male pancreato pancreatitis pain, fever pancreatic duct stone, ornithino
graphy duct with stented lytica
large stone
Fujimori 53/ No Chronic Abdominal 3.19 Dilated Pancreatic Stenotrop Relapsed

et al. [4] male pancreatitis, pain, fever pancreatic duct homonas 1 month
AML duct with cannulated maltophilia later and
stones and required
stented repeat
ERCP and
drainage
Fujinaga 70/ No Intraductal Abdominal N/A Mild Pancreatic Klebsiella Resolved
et al. [5] male mucinous pain, fever pancreatic duct oxytoca
neoplasm edema, cannulated
10 mm
pancreatic
stone
Aoki 50/ N/A Chronic Abdominal N/A N/A Purulent N/A Resolved
et al. [6] male pancreatitis pain, fever pancreatic
fluid, main
pancreatic
duct
stented
Wali 63/ Biliary Chronic Asymptomatic 6.04 Dilated Pancreatic E. coli, S. Resolved
et al. male sphincterotomy pancreatitis, pancreatic stricture, pneumoniae,
(this DM duct, stented and H.
case) pancreatic pneumonia
calcifications
Reproduced with permission from Wali et al. [17]

Context of the Case
83
Here again, the discussion focuses on explaining the differ-

ences in clinical presentation and bacteriology between the
six previous cases and the current case:
The presentation and severity of illness of AOSPD can vary sig-
nificantly. In prior cases, patients presented with abdominal pain,
with severity of illness ranging from meeting criteria for systemic
inflammatory response syndrome (SIRS) to septic shock. In con-
trast, our patient was asymptomatic and had no objective signs of
infection at the time of diagnosis and throughout his hospitaliza-
tion. Our case is also unique because of the polymicrobial nature
of the infection. Prior cases were monomicrobial. Two of the three
pathogens isolated in our case, Streptococcus pneumoniae and
Haemophilus influenza, are generally considered respiratory
pathogensSeveral theories to explain how respiratory patho-
gens may infect the pancreas have been proposed. Possible
hypotheses include hematogenous or lymphatic spread from
nasopharyngeal colonization, enteric spread from transient inclu-
sion of the bacteria in intestinal flora, or the direct introduction
of nasopharyngeal flora into the biliary tree and pancreatic duct
during endoscopic interventions such as ERCP [17].
Note again how placing the case in context showing how

this case is different from the others leads naturally to
hypothesizing about the reasons for the differences. This pro-
cess, the identification of unique features in a new case and
the development of a hypothesis to explain them, is abso-
lutely fundamental. Context and explanation are the heart
and soul of a case report.
Explanation of Events: Developing

a Hypothesis
Cases, writes Milos Jenicek, are uncontrolled experi-
ments. They do not provide proofs, but they generate
hypotheses [3]. A hypothesis is a supposition or proposed
explanation made on the basis of limited evidence. It is meant
only to be a starting point for further investigation, and is
never definitive; its aim is not proof, but rather plausibility.
Explanation of Events: Developing a Hypothesis 85
Developing a hypothesis is unquestionably the most difficult

part of writing a case report. It requires a deep knowledge of
all relevant anatomy, physiology, and pharmacology, a spark
of insight, and the creativity and persistence to test, revise,
and refine the hypothesis, so that it fits and explains the clini-
cal events.
Consider the serendipitous discovery, in 2008, that pro-
pranolol is a highly effective treatment for severe infantile
hemangiomas. A child with a severe nasal hemangioma
developed obstructive hypertrophic cardiomyopathy during
corticosteroid treatment, and was started on propranolol. By
the next day, the hemangioma had softened, and within
weeks it had faded and become almost completely flat.
Similar dramatic responses to propranolol were then observed
in 10 other children with severe hemangiomas. The authors
proposed three possible explanations for this unexpected
effect:
Potential explanations for the therapeutic effect of propranolol
a nonselective beta-blocker on infantile capillary hemangiomas
include vasoconstriction, which is immediately visible as a change
in color, associated with a palpable softening of the hemangioma;
decreased expression of VEGF and bFGF genes through the
down-regulation of the RAFmitogen-activated protein kinase
pathway (which explains the progressive improvement of the
hemangioma); and the triggering of apoptosis of capillary endo-
thelial cells [18].
This is a particularly strong hypothesis because it proposes

three plausible mechanisms, which explain both the rapid
improvement via vasoconstriction and the progressive
improvement over time with suppression of angiogenesis and
induction of apoptosis. The high explanatory value of the
hypothesis greatly strengthens the evidence value of the case
series and adds theoretical support for the clinical treatment
of hemangiomas with propranolol.
Another important function of a hypothesis is getting it
out there. When a case report is published, the hypothesis is
carefully scrutinized and may then be confirmed, debunked,
or enlarged upon by experts in the field. This is the reason
that even a tentative, incomplete, or highly speculative

hypothesis can still be useful. Others will evaluate it, propose
alternative or additional explanations, and make it stronger.
In my case report on cola-induced hypokalemia, I proposed
an osmotic diarrhea due to poor GI absorption of high-
fructose corn syrup as the likely cause of the hypokalemia [2].
A team of Greek authors then included my case report in
their review article and proposed several additional mecha-
nisms, including osmotic diuresis, hyperinsulinemia with
intracellular potassium redistribution, and caffeine-induced
phosphodiesterase inhibition and renal potassium wasting
[19]. Similarly, in the case of propranolol treatment for hem-
angiomas, a good initial hypothesis was made even stronger
through other researchers insights into propranolols molec-
ular mechanisms of action [20]. Thus the importance of pub-
lication: not only is the case made available as evidence, but
the hypothesis takes on an organic life of its own as it grows
and evolves over time.
The specific steps in developing a hypothesis are listed in
Table 7.6. First, establish the context of the case and specify
the rare or unique focus of the case that requires explanation.
Second, review all of the case reports, case series, and review
articles that pertain to your case, and critically evaluate the
existing hypotheses already developed by others. If an exist-
ing hypothesis seems sound, use it, but see if you can expand
on it or add other possible explanations for what you
Table 7.6 Steps in developing a hypothesis

Establish the context of the case what needs to be explained?
Review all pertinent case reports, case series, and review articles
Identify existing hypotheses, if any
Search the relevant basic science literature
Modify or add to existing hypotheses, or propose a new
hypothesis
Present the hypothesis and all supporting evidence in the
discussion
observed. (Remember that you must give full credit with cita-
tions for any hypothesis you borrow, or you will risk plagia-
rism.) If the existing hypotheses do not suffice, or there are
none, you will need to develop a new hypothesis. Third, go to
the basic science literature to find potential mechanisms,
pathways, anatomical variants, etc. to help explain the find-
ings. Often, this step will lead to revision or even rejection of
a favored hypothesis and development of a new explanation
that fits better with the underlying pathophysiology, pharma-
cology, or anatomy. Finally, present the hypothesis and all
supporting evidence in the discussion section of your case
report, making sure that it is clearly presented as a hypothesis
rather than a definitive explanation of events.
As an example of hypothesis development, consider the
case of a 65-year-old man who developed transient transcor-
tical motor aphasia in the setting of lithium toxicity [12]. The
key observation in this case was that the patient had halting
speech and inability to write, but comprehension and repeti-
tion were preserved. As the lithium levels dropped, the neu-
rologic symptoms resolved. Our first task was to put the case
in context:
A few cases of transient focal speech deficits and apraxia in the
setting of lithium toxicity have been reported in the literature,
including constructional dyspraxia, Wernickes aphasia,
pure-word deafness, and dysnomia. Our patient presented origi-
nally with confusion and word-finding difficulties, but his focal
aphasia persisted after his mental status improved. There were
problems with word finding, speech initiation, and handwriting
in the setting of preserved comprehension, repetition, reading,
and following commands. These findings are most consistent
with transcortical motor aphasia (TCMA). Our literature search
revealed no prior cases of TCMA associated with lithium
toxicity [12].
Next, we needed to evaluate the apparent causal associa-

tion between the patients lithium toxicity and his transient
TCMA. Were there any alternative explanations for this epi-
sode? A transient ischemic attack (TIA) seemed a reason-
able possibility; other TIA mimics such as seizures, migraine
headaches, and infectious or metabolic disturbances were
also considered. We reviewed the TIA literature and found

that non-atrial fibrillation patients with transient speech and
language disturbances without paresis were more likely to
have TIA mimics than true TIAs. Considering the strong
temporal association with lithium in the absence of seizure,
migraine, infection, or other metabolic disorders, lithium tox-
icity seemed to be the strongest possibility.
Having established the clinical likelihood of TCMA
from lithium toxicity, we needed a hypothesis to explain it.
This proved to be challenging. The few case reports of
speech and language disturbances in patients with lithium
toxicity did not give any convincing explanations. We
turned to both animal and human studies of lithium accu-
mulation and pharmacokinetics in the brain, including a
magnetic resonance spectroscopic study, and looked for
correlations with the anatomical regions (Brocas area and
the supplementary motor area) known to be associated
with TCMA. We discovered that these areas are watershed
zones between the blood supplies of the anterior and mid-
dle cerebral arteries:
Watershed zones are especially prone to ischemic injury, and may
have decreased rates of drug clearance. Given his poor baseline
cardiac output and dehydration in the setting of toxic lithium
levels, we hypothesize that this watershed area may have been
relatively hypoperfused, thereby reducing lithium clearance and
causing transient focal symptoms. When he was rehydrated and
lithium was held, local perfusion improved and his focal symp-
toms resolved [12].
This hypothesis may or may not be the true explanation

for lithium-induced TCMA, but the process establishing the
context of the case, a thorough literature review, and a rea-
sonable hypothesis built on the basic science lends plausi-
bility (and publishability) to the case report.
In the case of an 81-year-old man with metastatic gastric
carcinoma and type B lactic acidosis [21], we faced another
challenging hypothesis. Type B lactic acidosis typically
occurs in hematologic malignancies; it is rare in solid
malignancies, and ours was only the second case reported

in a patient with gastric cancer. Our review of the litera-
ture revealed several possible mechanisms, including thia-
mine deficiency, the Warburg effect (the tendency of tumor
cells to favor glycolysis even in the presence of sufficient
oxygen), and rapid tumor proliferation (usually seen in
hematologic malignancies) resulting in massive lactate
production, which overwhelms the bodys carbonic acid
bicarbonate buffer system. Our observation that this was
an extremely aggressive gastric carcinoma it was a poorly
differentiated AFP-positive tumor, with the liver almost
entirely consumed by metastases led to this hypothesis:
Given the extensive tumor burden and aggressive tumor
subtype, it is possible that the tumors overwhelming
anaerobic metabolism approximated that of a hematologic
malignancy. We then proposed two additional mecha-
nisms based on the patients extensive liver metastases and
chronic kidney disease:
Reduced lactate clearance may be an important pathophysio-
logic factor, as was likely in our case. Normally, the liver is
responsible for the clearance of 8090 % of lactate via the Cori
cycle, and extensive hepatic disease is therefore hypothesized to
impact lactate metabolismIt is possible that his baseline stage
III-IV CKD may have contributed to the systemic lactate accu-
mulation by impairing the secondary mechanism for lactate
clearance [21].
This is a good example of adapting the existing hypotheses

to a different scenario. The notion that an aggressive gastric
tumor can act like a hematologic malignancy is the key
inference behind the hypothesis.
In conclusion, a hypothesis can be original, adapted to fit
new circumstances, or borrowed intact. The original hypoth-
esis is the most difficult of the three, but also the most inter-
esting and satisfying to develop. A successful hypothesis
requires a thorough literature review, a clear understanding
of the context of the case, and the insight and creativity to
make a plausible explanation.
Speculation: The Broader Implications

In their article, The Function of the Discussion Section in
Academic Medical Writing, Skelton and Edwards conclude
that every paper must reach a conclusion that is not con-
tained in its results [22]. This is especially true for case
reports; if there is no speculation, the case narrative stands
alone, without interpretation or explanation. We have just
discussed one form of speculation, the hypothesis, which
attempts to explain the unusual events of the case. Sometimes,
it is advisable to go beyond explanation and speculate about
the broader implications of a case report. Often, this broader
speculation ties in with the surveillance and pharmacovigi-
lance functions of case reporting, which serve as a kind of
early warning system for new syndromes and serious
adverse drug reactions.
To stimulate speculation, ask these questions:
What are the implications of this case for the general

population?
How does it change our understanding of this disease,
drug, or procedure?
Does it offer any new scientific insights?
How might it affect future research?
Consider a few examples of speculation in case reports.

First, let us return to my patient with cola-induced hypokale-
mia. In considering the implications of the case for the gen-
eral population, I came to this conclusion:
Excessive soft drink consumption can cause hypokalemia due to

a fructose-induced osmotic diarrhea. Given the very high soft
drink consumption in industrialized societies, this is probably an
underreported and underdiagnosed cause of potassium depletion.
In addition to muscle weakness and cramping, hypokalemia low-
ers the arrhythmia threshold and may increase the risk of sudden
death, particularly in people with heart disease [2].
Although the Coca-Cola company was not happy with this

speculation (see Chap. 13), it is logical to consider the
Speculation: The Broader Implications 91
possibility that populations with heavy soft drink consump-

tion might see more complications of hypokalemia.
A case report of a lung cancer patient with acute abdomi-
nal pain after sexual intercourse led to this conclusion, with
implications for cancer patients in general:
Physicians should consider adrenal hemorrhage in the differential
diagnosis of any cancer patient presenting with acute abdominal
painActivities that increase intraabdominal pressure, such as
heavy lifting and sexual intercourse, may be risk factors for spon-
taneous adrenal hemorrhage [23].
The authors of a fascinating 2015 case report, of an AIDS

patient who developed cancer of nonhuman origin from a
clonal population of genetically altered tapeworm cells, appro-
priately emphasize the foundational implications of their case:
The host-parasite interaction that we report should stimulate

deeper exploration of the relationships between infection and
cancer [24].
In a case report of metformin-induced lactic acidosis in a

patient with normal renal function, I speculate on the exis-
tence of a subset of susceptible patients:
This case report adds to the evidence that metformin can trigger
lactic acidosis in a small subset of patients with normal renal func-
tion and no other evident risk factors. The cause is unclear, but an
otherwise subclinical inborn or acquired error of lactate metabo-
lism might predispose some metformin-treated patients to lactic
acidosis [13].
Note, again, the natural flow from context to hypothesis to

broader implications. All that remains of the discussion, once
all of these pieces are in place, is the teaching point.
The Teaching Point

The teaching point, which traditionally concludes a case
report, should be simple, clear, and memorable. It should call
to mind the pithy and powerful aphorisms of Hippocrates
(see Chap. 2). Typically, it begins with a phrase such as
Physicians should be aware or Clinicians should con-

sider, and consists of a single sentence. It is generally best
to have one main teaching point; a second is acceptable if
there are two equally important lessons to be learned. More
than two teaching points begins to strain the memory of the
reader and tends to dilute the message. In writing the teach-
ing point, the author should simply ask: What is the main
point of this case report? What message do I want readers to
take away from it? In the spirit of teaching by example, here
are the teaching points from several of the case reports
already discussed in this chapter:
Physicians should ask their patients about soft drink consumption

when faced with unexplained hypokalemia [2].
Physicians should discuss the possibility of impairment of vibrato
with string musicians before prescribing a -blocker for
hypertension or other conditions that require long-term, daily
use [4].
Clinicians should be alert to the possibility of vertebral sarcoid-
osis in any patient with a remote sarcoidosis history and persis-
tent back pain [6].
We think it is important to make clinicians aware of the possibility
of rare but severe hemolysis with metformin treatment [10].
In lithium-treated patients who develop transient aphasia, physi-
cians should consider the possibility of lithium toxicity, espe-
cially in the setting of volume depletion, renal failure, or
overdosage [12].
Physicians should be alert to the possibility of lactic acidosis in
any metformin-treated patient with an unexplained anion
gap metabolic acidosis, regardless of risk factors and renal
function [13].
This case demonstrates that there may be a small subset of (dialy-
sis) patients for whom direct contact with polysulfone results
in thrombocytopenia [15].
Physicians should be aware that type B lactic acidosis can occur in
a variety of nonhematologic tumors, including gastric carci-
noma [21].
Note that the teaching point often generalizes and broad-

ens the message of the case, and tends to arise quite naturally
from the discussion of context, the hypothesis, and the specu-
lation that precede it.
The CARE Guidelines and Checklist 93
The CARE Guidelines and Checklist

The CARE (CAse REport) guidelines (Fig. 7.4) were devel-
oped in 2013 in response to evidence that many case reports
are insufficiently rigorous to be aggregated for data analysis,
inform research design, or guide clinical practice [7]. The
authors used a three-stage consensus process involving 27
participants, which resulted in a 13-item checklist as a case
reporting guideline [7, 25].
Compliance with the CARE guidelines not only improves
the evidence value of the case report, but may as the guide-
lines continue to gain acceptance also increase the likeli-
hood of publication. I recommend that authors complete the
checklist and mention when submitting the case report that it
complies with CARE guidelines.
Figure 7.4 The CARE checklist of information to include when writing

a case report (2016) (Reproduced with permission from Elsevier [25])
References
1. Sagi I, Yechiam E. Amusing titles in scientific journals and arti-
cle citation. J Inform Sci. 2008;34(5):6807.
sumption: a case report. Cases J. 2008;1:32.
4. Packer CD, Packer DM. Beta-blockers, stage fright, and vibrato:
a case report. Med Probl Perform Art. 2005;20(3):12630.
5. Chiang E, Packer CD. Concurrent reactive arthritis, Graves
disease, and warm autoimmune hemolytic anemia: a case report.
Cases J. 2009;2:6988.
6. Packer CD, Mileti LM. Vertebral sarcoidosis mimicking lytic
osseous metastases: development 16 years after apparent resolu-
tion of thoracic sarcoidosis. J Clin Rheumatol. 2005;11(2):
1058.
7. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines:
consensus-based clinical case reporting guideline development.
8. Rison RA. A guide to writing case reports for the Journal of
Medical Case Reports and Biomed Central Research Notes.
9. Iacopetti C, Packer CD. Cannabinoid hyperemesis syndrome: a
case report and review of pathophysiology. Clin Med Res.
2014;12(12):657.
10. Packer CD, Hornick TR, Augustine SA. Fatal hemolytic anemia
associated with metformin: a case report. J Med Case Rep.
2008;2:300.
11. Choe MJ, Packer CD. Severe romiplostim-induced rebound
thrombocytopenia after splenectomy for refractory ITP. Ann
Pharmacother. 2015;49(1):1404.
12. Katz RB, Packer CD. Lithium toxicity presenting as transient
transcortical motor aphasia: a case report. Psychosomatics.
2014;55(1):8791.
13. Packer CD. Metformin-associated lactic acidosis in a patient
with vertebral artery dissection. South Med J. 2006;99(10):
11478.
14. Reinke CE, Resnick AS. Incarcerated appendix in a spigelian
hernia. J Surg Case Rep. 2010;10:3.
References 95
15. Muir K, Packer CD. Thrombocytopenia in the setting of dialysis

using biocompatible membranes. Case Report Med.
2012;2012:358024.
16. U.S.-acquired human rabies with symptom onset and diagnosis
abroad, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(39):
77781.
17. Wali E, Koo P, Packer CD. Acute obstructive suppurative pan-
creatic ductitis in an asymptomatic patient. Case Rep Med.
2015;2015:919452.
18. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi
F, Thambo J, Taieb A. Propranolol for severe hemangiomas of
infancy. N Engl J Med. 2008;358:264951.
19. Tsimihodimos V, Kakaidi V, Elisaf M. I Cola-induced hypokalae-
mia: pathophysiological mechanisms and clinical implications.
Int J Clin Pract. 2009;63(6):9002.
20. Storch CH, Hoeger PH. Propranolol for infantile haemangio-
mas: insights into the molecular mechanisms of action. Br
J Dermatol. 2010;163(2):26974.
21. Krimmel JD, Packer CD. Type B lactic acidosis in the setting of
gastric adenocarcinoma with extensive metastases. Med Princ
Pract. 2015;24:3913.
22. Skelton JR, Edwards SJ. The function of the discussion section in
academic medical writing. BMJ. 2000;320(7244):126970.
23. Wang J, Packer CD. Acute abdominal pain after intercourse:
adrenal hemorrhage as the first sign of metastatic lung cancer.
Case Report Med. 2014;2014:612036.
24. Muehlenbachs A, Bhatnagar J, Agudelo CA, et al. Malignant
transformation of Hymenolepsis nana in a human host. N Engl
J Med. 2015;373(19):184552.
25. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. The
CARE guidelines: consensus-based clinical case report guideline
development. J Clin Epidemiol. 2014;67(1):4651.
Chapter 8
Special Considerations
Clifford D. Packer
Adverse Drug Reaction Case Reports
Whenever a patient presents with new symptoms or abnormal

laboratory results, an adverse drug reaction (ADR) should be
considered in the differential diagnosis. ADRs are common; it
has been estimated that 38 % of hospitalized patients are
admitted because of ADRs, and about 7 % of hospitalized
patients will experience a serious ADR during their stay [1].
Most ADRs are of the type known as dose related or aug-
mented, in which there is an exaggerated response to the
known pharmacologic action of the drug; bleeding with warfa-
rin and orthostatic hypotension from antihypertensive drugs
are examples of these common ADRs, which are seldom
reportable. Non-dose related or bizarre ADRs, which are
uncommon, not related to the known pharmacologic action of
the drug, and unpredictable, are more likely to be reportable
[2]. Examples of this type include anaphylaxis to penicillin,
malignant hyperthermia with general anesthetics, and (on a
more delayed basis) osteonecrosis of the jaw with bisphospho-
nates or the teratogenicity of thalidomide.
Case reports describing ADRs have a vital role in pharma-
covigilance. Before a new drug is approved for general use,
phase II and phase III trials assess efficacy and safety in a few
hundred to a few thousand subjects. When the drug is released

DOI 10.1007/978-3-319-41899-5_8
98 Chapter 8. Special Considerations
to the general population and used by tens or hundreds of

thousands of patients, rare and often unanticipated adverse
effects may begin to emerge. These effects can be quite severe,
as for example, in the cases of troglitazone-induced liver fail-
ure and valvular heart disease associated with fenfluramine-
phentermine. Case reports of ADRs are a critical part of this
postmarketing surveillance also known as phase IV trials
in which rare adverse effects that were not detected in early
clinical trials can be reported and verified.
Since ADR case reports rely largely on temporal connec-
tions to support causality, a timeline (either a figure or table;
see Chap. 7) should be created to show the temporal relation-
ship between the drug and the adverse effect. A simple time-
line describing the effects of two different dialyzer types on
platelet counts is shown in Fig. 7.2. A more complex timeline
(Fig. 8.1), created by one of my medical student co-authors,
illustrates the effects of five drugs, platelet transfusions, and
splenectomy on the long-term platelet counts of a patient
with refractory ITP [3]. The aim of this timeline is to show
how platelet counts were affected when romiplostim was
held at the time of splenectomy. A large amount of informa-
tion is given in a single, easy-to-understand figure. This clari-
fies the timeline and allows the authors to focus on
interpretation, as the reader can refer back to the figure for
the day-by-day details of treatment and response.
The key to writing a convincing and publishable ADR case
report is to make a compelling argument for the causal rela-
tionship between the drug and the adverse effect. In addition
to the timeline, this requires a discussion of differential diagno-
sis and possible alternative explanations, and use of a validated
causality scale to support the argument, such as the Naranjo
ADR Probability Scale [4], the WHO-UMC causality catego-
ries [5], or the Liverpool adverse drug reaction causality tool
[6]. Because it is simple, transparent, and easy to apply, the
Naranjo scale (Table 8.1) is probably the most commonly used
causality scale. Naranjo adds points for previous conclusive
reports of the same reaction, temporal relationships between
the drug and the event, lack of alternative causes, response to
challenge and dechallenge, and other objective evidence such
Adverse Drug Reaction Case Reports 99
Platelet clinical course

450
400
350
300
Platelet Count in 109 Liter
250
200
Splenectomy Romiplostim held
romiplostim held
150
100
50
0
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
Days
Pred (mg)
40 40
Dexa (mg)
40 40 40 40
IVIG (mg/kg)
0.5 0.5 0.5 1.0
Plat (units)
2 2 2 2 2
Rom (ug/kg)
1 1 1 1 2 3 4 5 6 7 8 8 8 8 8 8 8 8 8 8 8 8 8 8
Ritux (mg)
675 675 675 675
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
Figure 8.1 Top graph represents patients platelet counts through-

out the clinical course. Bottom graph represents the temporal rela-
tionship of doses of important pharmacotherapeutic agents. Each
bar represents a single dose for a given day. Labels include drugs
with the corresponding units of doses. Abbreviations: Pred predni-
sone, Dexa dexamethasone, IVIG intravenous immunoglobulin, Plat
platelets, Rom romiplostim, Ritux rituximab (Reproduced with per-
mission from SAGE Publications [3])
as toxic drug levels in the blood. Points are subtracted if there

are alternative causes for the reaction, or if the reaction reap-
peared when a placebo was given. Case reports with definite
or probable Naranjo scores are more likely to be published
than those with possible scores. For drug interaction case
reports, the Horn Drug Interaction Probability Scale (DIPS)
has many of the same elements as the Naranjo scale, but also
Table 8.1 The Naranjo ADR probability scale

Yes No Unknown Score
Are there previous conclusive +1 0 0
reports on this reaction?
Did the adverse event appear +2 1 0
after the suspected drug was
administered?
Did the adverse event +1 0 0
improve when the drug was
discontinued and a specific
antagonist was administered?
Did the adverse reaction +2 1 0
reappear when the drug was
readministered?
Are there alternative causes 1 +2 0
(other than the drug) that
could on their own have
caused the reaction?
Did the reaction reappear 1 +1 0
when a placebo was given?
Was the drug detected in the +1 0 0
blood (or other fluids) in
concentrations known to be
toxic?
Was the reaction more severe +1 0 0
when the dose was increased
or less severe when the dose
was decreased?
Did the patient have a +1 0 0
similar reaction to the same
or similar drugs in any
previous exposure?
Was the adverse effect +1 0 0
confirmed by any objective
evidence?
Adapted with permission from John Wiley and Sons [4]
Assessment score: Definite 9; Probable 58; Possible 14;
Doubtful 0
Adverse Drug Reaction Case Reports 101
includes questions on whether the observed interaction is con-

sistent with the known interactive properties of both the pre-
cipitant drug and the object drug [7]. For authors who are not
pharmacologists, answers to these questions will require addi-
tional research on the properties of both drugs.
In the discussion section of an ADR case report, all previ-
ous reports of the drug reaction should be reviewed and
compared with the current report; causality including possi-
ble alternative explanations should be explored; and a
hypothesis for the mechanism of the reaction should be pro-
posed. The following passage gives the argument for azathio-
prine hypersensitivity in a patient with Crohns disease, with
recurrent fever, and concludes with the Naranjo score:
The differential diagnosis for fever in a patient with IBD on
immunosuppressive medications focuses primarily on infectious
etiologies. In this patient, possible localizing clues for infection
proved to be red herrings: the opacity on CXR was likely from
atelectasis, and the rising bilirubin and elevated aminotransfer-
ases were due to the hypersensitivity reaction rather than biliary
tree disease. In addition to the fever and leukocytosis, our
patients arthralgias and rash raised concern for extraintestinal
manifestations of IBD flare. However, our patient did not have
worsening intestinal IBD symptoms; moreover, he clinically
improved after each flare without any specific intervention
targeting IBD. Ultimately, it was only after the third admission
with still no evidence of an infectious etiology that the possibility
of AZA hypersensitivity was considered in earnest. The associa-
tion became clear by aligning the timing of his fevers with the
timing of AZA ingestion. Further evidence of AZA hypersensi-
tivity included clear clinical improvement each time the AZA was
stopped and the escalating clinical and laboratory manifestations
that occurred with each rechallenge. This intensifying response
with each exposure is a hallmark of hypersensitivity reactions.
The Naranjo scale score was 8, supporting the probability that this
was a true adverse drug event [8].
As another example, consider this argument in support of

iatrogenic Cushings syndrome due to an interaction between
ritonavir and oral budesonide:
Our patient developed edema, weight gain, uncontrolled hyper-
tension, cushingoid facies, hypokalemia, and metabolic alkalosis
shortly after initiation of budesonide, with resolution of all symp-
toms soon after it was stopped. Congestive heart failure, liver
disease, and nephrotic syndrome were ruled out as causes of the

edema, which supported iatrogenic Cushings syndrome. Although
budesonide concentrations were not measured, the very low
serum cortisol level (0.8 g/dL) in a clinical setting of hypercorti-
solism provides strong indirect evidence that levels of an exoge-
nous corticosteroid (i.e., budesonide) were high. Adrenal
suppression has been described in a number of cases of iatrogenic
Cushings disease due to ritonavir-steroid interactions. The
Naranjo Probability Scale and Horn Drug Interaction Probability
Scale score characterized this as a probable drug interaction [9].
Note that the Naranjo scale can serve as an excellent outline

for the discussion section of an ADR case report. Point-by-point
answers to the ten Naranjo questions (or to as many as are
answerable), with full explanations for each answer, will require
a full literature review and a thorough investigation of causal-
ity which, according to the published guidelines of Kelly et al.
[10], are the two essential features of an ADR case discussion.
Many ADR case reports are published, but they vary
greatly in terms of quality and clinical usefulness. Several
studies indicate that ADR case reports are frequently missing
important elements, including route and formulation of the
suspect drug, social history, weight, race, allergy history, liver
and kidney function, discussion of possible mechanisms for
the ADR, and use of objective rating scales to support the
causal connection between drug and adverse effect [1113].
Consequently, guidelines for submitting ADR case reports
have been developed that include all relevant patient data
and drug information, a full description of the adverse event,
a review of previous reports in the literature, and an assess-
ment of competing explanations and biologic plausibility [10].
All of these elements should be included in every ADR case
report. Incomplete or unsubstantiated case reports are sel-
dom published and have no role in pharmacovigilance.
N-of-1 Trials
The n-of-1 trial is a first cousin of the case report. N-of-1 trials
use individual patients as study subjects, with the purpose of
finding the best treatment for that individual using his or her
N-of-1 Trials 103
own data. In essence, n-of-1 trials explore variability in an

objective way, and serve as a way to make individual case
reports more useful and more generalizable. Some n-of-1 tri-
als use blinding, placebo controls, crossover designs, and wash-
out periods sequentially in a single patient [14]; others involve
in-depth studies of the genomic or physiologic characteristics
of a single interesting or unusual case. Although randomized
controlled trials (RCTs) are generally considered the best
evidence for evaluating the effectiveness of treatments or
procedures, n-of-1 trials have important advantages, which are
becoming increasingly clear in the era of genomic medicine
and individualized treatment. Unlike RCTs, which may evalu-
ate thousands of patients but study only a few variables, n-of-1
trials can better comprehend the myriad factors and nuances
involved in a patients response to treatment.
Any physician in active practice performs de facto n-of-1
trials every day, for example, in the selection, dosing, and
titration of blood pressure medicines for a number of indi-
vidual patients. Factors such as race, age, gender, comorbid
conditions, renal function, medication adherence, potential
side effects, financial constraints, and patient preferences all
come into play. These factors are too complex to be assessed
in toto by any RCT, however large and well-designed. RCTs
may reveal the best treatment for a population of patients,
but there are always substantial numbers of individuals who
will not benefit a state of affairs which Nicholas J. Schork
has described as imprecision medicine [15]. The n-of-1
trial is designed to work in the opposite direction, from the
particular to the general, identifying the traits of individuals
and small groups of patients that would predict a favorable
response to treatment. The treatment can then be general-
ized to larger populations of patients with the same traits,
with more precision and fewer nonresponders.
There are several exciting examples of this kind of thinking
in oncology, especially in the study of the small numbers of outli-
ers who respond exceptionally well in clinical trials. In the past,
these rare super-responders were dismissed as anecdotal
cases, but more recently, intensive genomic studies of these
patients have revealed that specific genetic mutations, such as
the ROS1 gene rearrangement in non-small cell lung cancer and

the mutated EGFR gene in colon cancer, are predictors of excel-
lent treatment responses (to crizotinib and cetuximab, respec-
tively). These findings are driving cancer researchers to revisit
failed clinical trials to find and reassess more outliers [14]. In
2012, the National Cancer Institute announced the Exceptional
Responders Initiative to identify and sequence the tumors from
100 extraordinary responders to any type of cancer therapy [16].
The aim is to collect and curate n-of-1 cases to create a large
genomic database that can be used for clinical decision-making
[17]. Conversely, reports of adverse reactions to commonly used
drugs such as clopidogrel, warfarin, and carbamazepine have led
to the discovery of genetic variations which can put patients at
risk. This has prompted the FDA to relabel many drugs with
pharmacogenomic information [18, 19]. Beyond pharmacoge-
nomics, the use of wireless remote phenotypic monitoring
devices such as smartphone apps for heart rate and sleep qual-
ity, actigraphs, continuous glucose monitors, esophageal pH sen-
sors, heart rhythm monitors, oximeters, and wrist tremor
monitors for Parkinsons disease expands the possibilities for
accurate and comprehensive physiologic data collection in
n-of-1 trials of treatment response [14].
What, then, is the connection between case reports and
n-of-1 trials? Case reports tend to focus on the unusual outli-
ers, adverse drug reactions, new syndromes, atypical presenta-
tions and often raise questions that would be best answered
by n-of-1 trials. For example, there are numerous case reports
of prazosin as an effective treatment for PTSD-associated
nightmares; the results of randomized controlled trials have
been mixed [20]. Clearly, some patients benefit, but many do
not. Carefully designed n-of-1 trials, with the fullest possible
accounting for the many variables in these complex patients,
might reveal which patients are most likely to benefit; for
those unlikely to benefit, the side effects of prazosin could be
avoided. In any case report, it is important to speculate on the
broader implications, including directions for future research.
Therefore, the potential for n-of-1 trials (or other studies) to
resolve questions raised by the case should be noted and con-
sidered in the case report discussion.
Case Series 105
In a larger sense, case reports, like n-of-1 trials, work

inductively: they go from the specific to the general. N-of-1
trials can be aggregated and subjected to meta-analysis,
which can lead to valid general conclusions. Case reports are
already aggregated in a huge database, with more than 1.7
million cases indexed in PubMed and can be used effec-
tively for clinical decision-making when other sources of
evidence are lacking.
Case Series
The case series is a group or series of observations involving
patients with a similar diagnosis or cluster of symptoms, or a
similar response (adverse or beneficial) to a procedure or
treatment. In the epidemiology literature, the definition and
design of the case series are largely neglected; in one survey
of epidemiology textbooks, only five of 27 even mention case
series in the index [21]. The minimum number of cases
required for a case series is also unclear [22]; although some
authors have argued for the rule of four [23], many pub-
lished case series consist of only two or three cases. The case
series is distinguished from case-control and cohort studies in
that it lacks a comparison or control group, and does not fol-
low patients over time using a well-defined inception point
[21, 24]. This limits its statistical analysis to means, medians,
ranges, and graphs, whereas case-control studies can include
calculations of odds ratios and absolute risk reduction.
The aims and functions of case series are similar to those
of case reports: to recognize and describe new diseases or
rare manifestations of disease, detect drug side effects, study
mechanisms of disease, and assist with medical education. In
addition, case series are useful in case definition, clues
about cause, single physician or hospital reports of out-
comes, and in the development of trend or benchmarking
analyses and multi-institutional registries [25]. Case series
can offer more compelling evidence than case reports,
because clusters of new or unusual cases are more convinc-
ing than isolated cases. Case series can thus function quite
persuasively as hypothesis-generating studies, which lead to

additional trials for confirmation. A good example of this is
the 2008 case series which showed the effectiveness of sys-
temic propranolol in treating severe infantile hemangiomas
[26]. This led to additional case series, physiologic studies,
randomized controlled trials, a meta-analysis, and finally
widespread acceptance of propranolol as a first-line treat-
ment. Similarly, it was the case series of Pneumocystis carinii
pneumonia and Kaposis sarcoma that led to an immune
suppression hypothesis and the eventual discovery of the
AIDS virus.
On the other hand, case series have their disadvantages.
One major drawback is the lack of a comparison group, which
makes questions of cause and effect, disease frequency, and
treatment effectiveness impossible to answer without further
studies. Also, case series are subject to selection bias, because
the investigator self-selects the cases [27]. Because of these
weaknesses, case series can cause useful treatments to be
abandoned, or potentially harmful procedures to be adopted
[28]. Consider the 1998 series of 12 cases by Wakefield et al.
which postulated a relationship between measles, mumps,
and rubella (MMR) vaccination and chronic enterocolitis
and regressive developmental disorder in children [29]. This
paper was found to be fraudulent and was subsequently
retracted, and any connection between MMR vaccination
and autism was debunked in several epidemiologic studies.
However, the harm has persisted because the notion of
vaccine-induced autism has gained some traction in the pop-
ular culture. This has led to reduced vaccination rates and
preventable outbreaks of measles, mumps, and whooping
cough over the past several years.
Although a series of cases can be collected from multiple
sources, a single source may be better because it permits the
use of uniform clinimetric criteria to compare and interpret
the cases [25]. The authors may report only cases they have
observed themselves, or assemble cases from several clinical
sites. Case series can be cross-sectional studies, that is, an
instant portrait of case characteristics at a set time, or longi-
tudinal, with cases tracked as they arise over time. Longitudinal
Case Series 107
case series give a better understanding of the clinical course

and clinical outcomes [25].
When writing up a case series, the basic structure is the
same as that for the traditional case report, which is discussed
in detail in Chap. 7. For the majority of case series reports,
which are descriptive studies involving only a few patients
with no statistical testing, a Methods section is not required.
However, in more complex case series involving large num-
bers of patients and statistical analysis, a brief Methods or
Patients and Methods section should be added after the
introduction and before the case descriptions. This should
include the number of cases described, the time period and
length of follow-up, inclusion and diagnostic criteria, method
of assessment, description of statistical analysis, and patient
consent and/or IRB approval, as required. For example, in a
case series of rheumatic fever presentation and outcome in
Brazil from 1986 to 2007, 178 cases were diagnosed, of which
134 were selected; inclusion criteria were age under 18 years,
fulfillment of Jones criteria, and regular follow-up for at least
1 year; all cases were followed up by one author, descriptive
statistics were given for continuous variables, and the proba-
bilities of relapse and carditis were assessed with clinical and
echocardiogram data and actuarial survival analysis [30].
The case descriptions should be a series of short para-
graphs with all essential demographic, clinical, and clinimetric
data included for easy comparison. In case series where there
are too many reports to list individually, a couple of case
descriptions are often included as examples, followed by a
summary of all the cases with a listing of the important clini-
cal observations. For instance, in a 1981 series of eight male
homosexual patients with Kaposis sarcoma, two brief case
descriptions are given; of the group as a whole, we learn that
seven had generalized lymphadenopathy, six had visceral
involvement, one had possible brain involvement, three died
from Kaposis sarcoma, and one died from overwhelming
cryptococcosis unresponsive to antifungal therapy. A com-
parison table is included with patient age, ethnic group, sites
of skin and visceral lesions, CMV and hepatitis B titers, dis-
ease duration, chemotherapy, and outcome [31].
For any case series, a comparison table is essential. Unlike

a single case report, where the table compares the object case
with similar cases from the literature, the case series uses the
table to make an internal comparison of its own cases.
Table 8.2 illustrates the serum renin levels, aldosterone levels,
and abdominal ultrasound findings for a series of seven Indian
children with childhood Bartters syndrome [32]. In the dis-
cussion, the authors compare the clinical and biochemical
features of their patients with other case series of Bartters
syndrome in children, and note that a series of 13 Arabic chil-
dren also showed hypokalemia, hypochloremia, metabolic
alkalosis, and hyperreninemia in all cases. They conclude just
as in a single case report with the important teaching points:
Bartters syndrome should be suspected in any child with
history of failure to thrive and metabolic alkalosis. Early diag-
nosis and treatment with NSAIDs are lifesaving.
In summary, the case series is a simple, accessible, and inex-
pensive way to describe new or emerging diseases, treatments,
Table 8.2 Serum renin, aldosterone, and renal ultrasound findings

in seven children with childhood Bartters syndrome
Serum Serum
renin (ng/ aldosterone
Case# ml/h) (ng/l) Ultrasound abdomen finding
1 8.5 330 Normal
2 187 848.7 Bilateral medical renal
disease
3 6.05 1400 Normal
4 3.23 86.3 Bilateral mildly increased
renal cortical echoes
5 8.6 752 Normal
6 40.71 967 Nephrocalcinosis
7 4 135 Normal
Mean 36.8 42.3 645 482.7
Adapted with permission from Sampathkumar et al. [32]
How to Write a Clinical Images Article 109
or drug side effects, and generate hypotheses for further study.

Limitations of case series include potential for selection bias,
lack of a control group, lack of generalizability, and potential
for harm with incorrect conclusions (the anecdotal fallacy).
Case series follow the same basic structure as single case
reports, except that a Methods section is sometimes needed
to describe case selection and statistical analysis, and the dis-
cussion must include an internal comparison of case charac-
teristics in addition to a review of the literature. As in any case
report, the three main objectives are to place the cases in
context, develop a hypothesis to explain the findings, and
make a teaching point.
How to Write a Clinical Images Article

A good clinical image that really tells the story makes for
a more compelling and convincing case report. I have used
photographs, CT, MRI, and PET scan images, and pathology
photomicrographs in my own case reports. Increasingly, real-
time videos, echocardiograms, ultrasounds, phonocardio-
grams, angiograms, and other media are becoming the norm
in the era of the online electronic case report. A good image,
whether static or dynamic, can also save hundreds of words of
description, which makes for a leaner and more succinct case
report. Editors love to publish cases with powerful images;
they also love short, concise articles. Increasingly, they are
making the image the centerpiece, and shrinking the case
report to a mere caption. In many journals, in fact, the clini-
cal images article seems to be replacing the traditional case
report. Therefore, although I shudder to consider a possible
Fahrenheit 451 future for the case report (all images, no
words), I do think it is important for physicians to know how
to publish their most captivating clinical images.
Contrary to many physicians expectations, the rarest,
oddest, and most extreme images are not necessarily the
most publishable. In fact, a review of the Images in
Clinical Medicine section of the New England Journal of
Medicine (NEJM) reveals a substantial number of common

medical conditions (measles, rubella, myxedema, SVC syn-
drome) and findings (pronator drift, upper limb clonus,
cannon A waves, pulsus alternans) among the oddities such
as a Grynfeltt hernia, ptosis due to impacted fish mandibles
over the eye of a swimmer who collided with a school of
fish, and bilateral periorbital erythema migrans in a boy
with disseminated Lyme disease. In its instructions for
authors, NEJM calls for classic images of common medical
conditions, with the aim to capture the sense of visual
discovery and variety that physicians experience [33]. This
notion of archetypal images of common conditions is a
common theme in many journals. BMJ is very clear about
the kinds of images it does not want: foreign bodies,
results of gross trauma, poor image quality (even if inter-
esting), simply textbook presentations, very rare clinical
presentations, and submissions which simply criticize other
physicians, or the patient [34]. The Lancet solicits visual
information that will be useful to other physicians, as well
as interesting, educational, and respectful of the patient;
they are less interested in pictures that simply illustrate an
extreme example of a medical condition [35]. Finally, the
Canadian Medical Association Journal (CMAJ) asks for
intriguing, classic, or dramatic images which illustrate
common presentations of rare conditions, or unusual pre-
sentations of common problems [36]. These instructions
give much latitude for various kinds of images, but the com-
mon thread seems to be that beyond amazing, amusing, and
impressing us, the best clinical images should have some-
thing important to teach us. In other words, novelty is
important, but so is the clinical lesson, the teaching point.
In this way, clinical image articles are very much like case
reports.
In general, the captions for clinical images are limited to
100450 words, depending on the journal. The caption,
according to the Lancet, should give a brief patient history,
How to Write a Clinical Images Article 111
put the image in context, and explain what the image shows
and why it is of interest to the general reader [35]. This may
involve further discussion of epidemiology, differential diag-
nosis, management strategies, prognosis, or other issues raised
by the image. For example, a recent NEJM Images in
Clinical Medicine article includes a video of a patient with
cannon A waves, an ECG showing AV nodal re-entrant
tachycardia with characteristic notching in the terminal por-
tion of the QRS in lead V1, a brief discussion of the patho-
physiology and differential diagnosis for cannon A waves,
electrophysiology study results, and the clinical course includ-
ing follow-up after slow pathway ablation [37]. Impressively,
all of this information is conveyed in a 222-word caption.
Brevity is the key with clinical images: as much as possible, let
the picture speak for itself.
How does one find publishable clinical images? As Louis
Pasteur said, chance favors the prepared mind. Stay vigi-
lant, carry a smartphone in your office and on rounds, and
be prepared to request written consent before recording
any patient images. Be alert not only for the unusual and
bizarre, but for archetypal images of common diseases and
exemplary physical exam findings. Make creative use of
videos and real-time monitoring devices in addition to pho-
tographs and standard imaging studies. Use more than one
modality to increase the power and persuasiveness of your
images; for instance, in the case of a patient with a classic
paradoxical S2 split caused by a left bundle branch block,
include a phonocardiogram with respiratory tracings along
with the standard 12-lead ECG. Above all, stay curious; the
best reason to photograph an unexpected lesion is to pre-
serve it, study it, and finally diagnose it. If the diagnosis is
elusive, find the pathologist or dermatologist or whoever
else can help you to nail it down. Like case reports, clinical
images are almost never publishable without a diagnosis.
Your helpful colleague will be happy to sign on as a
co-author.
The Clinical Quiz or Mystery Image

Another common way to present an image is in the form of a
clinical quiz, where a brief history is given in the image cap-
tion, followed by one or more questions (usually multiple
choice) to test the readers knowledge. Answers with expla-
nations are given separately. One of my best medical students
published the following clinical image article based on a
patient she cared for on the wards during her internal medi-
cine clerkship (see Fig. 8.2 and accompanying text).
Note the paradoxical title: When Asthma is Not Asthma.
If this were a simple clinical images article without the quiz,
a straightforward title such as Post-intubation tracheal ste-
nosis would be most appropriate (see my comments on case
report titles in Chap. 7). However, this title is apt because a
clinical quiz or mystery image works better with an ironic,
mysterious, or humorous title to preserve uncertainty and
entice the reader to solve the mystery.
When Asthma is Not Asthma

A 52-year-old woman with a five-pack-year smoking history
was admitted to the hospital with persistent shortness of breath,
wheezing, and dry cough of 2 weeks duration following an upper
respiratory infection. Her medical history was notable for a
72-hour intubation for hypoxic respiratory failure secondary to a
drug overdose months prior. She had never been hospitalized for
shortness of breath in the past. She was prescribed an albuterol
inhaler for seasonal allergies. She is now using her albuterol inhaler
four times a day with minimal relief of her symptoms. During her
admission to the hospital, she was given albuterol and ipratropium
nebulizers and discharged to home to complete a 5-day course of
prednisone for a presumed asthma exacerbation. She returned to
the emergency department 5 days later when her symptoms per-
sisted. Lung auscultation revealed mild bilateral expiratory wheezes
and stridorous breath sounds on exertion. The rest of her physical
exam was unremarkable. Her chest radiograph was normal. On
spirometry, her flow-volume loop demonstrated marked limitation
of the inspiratory and expiratory flow, consistent with fixed
obstruction. Flexible laryngoscopy revealed 80 % tracheal stenosis
at the third tracheal ring. Computer tomography (CT) of the chest
and neck with contrast confirmed the presence of a stenosis in the
mid-trachea with an area of 6 mm by 3 mm (Fig. 8.2).
The Clinical Quiz or Mystery Image 113
Figure 8.2 Sagittal CT view of the chest and neck revealing severe
mid-tracheal stenosis (Reproduced with permission from Strohl and
Packer [38])
What is the most significant risk factor for the develop-

ment of post-intubation tracheal stenosis?
Cuff pressure and volume
History of GERD
Female sex
Concurrent use of corticosteroids
No previous intubations
Since this is an online journal, the reader is prompted to

click on the best answer. Once a selection is made, the per-
centage of readers who selected each answer appears:
Cuff pressure and volume (72.31 %)
History of GERD (15.38 %)
Concurrent use of corticosteroids (7.69 %)
No previous intubations (3.08 %)
Female sex (1.54 %)
The reader is then directed to view the answer and
explanation:
Answer: A. Cuff pressure and volume
MCQ Explanation:
The diagnosis of tracheal stenosis should be considered in
patients with a recent history of intubation who are presenting
with new or worsening respiratory symptoms. It is commonly
misdiagnosed as an asthma or COPD exacerbation, which
results in delayed diagnosis and treatment. Cuff pressure and
volume are the most significant predictors of the development
of post endotracheal intubation tracheal stenosis. When steno-
sis develops, it most often occurs at the level of the endotra-
cheal tube cuff. The cuff exerts pressure on the tracheal wall,
leading to mucosal ischemia and ulceration, and eventual
development of chondritis and fibrosis. Fortunately, the devel-
opment of large-volume, low-pressure cuffs has markedly
reduced the occurrence of tracheal stenosis. Other factors con-
tributing to the development of stenosis include length of intu-
bation, traumatic intubation, history of previous intubations,
excessive corticosteroid use, advanced age, female gender,
severe respiratory failure, severe reflux disease, autoimmune
diseases, obstructive sleep apnea, and previous radiation ther-
apy to the neck or chest.
After diagnosis, this patient was continued on albuterol and
ipratropium nebulizers and restarted prednisone with mild
improvement of her symptoms. She later underwent tracheal
resection with no complications [38].
Note that the typical clinical scenario, pathophysiology,

risk factors, and treatment for post-intubation tracheal steno-
sis are all briefly discussed, and the important teaching
point that tracheal stenosis is commonly misdiagnosed as
The Clinical Quiz or Mystery Image 115
an asthma or COPD exacerbation, which delays diagnosis

and treatment is clearly stated. The multiple-choice ques-
tion is neither too difficult nor too easy, but at the appropri-
ate level for a trainee or generalist physician reading a
general medicine journal.
Subspecialty-level questions, on the other hand, should be
reserved for subspecialty journals. Here is an example of a
challenging multiple-choice question aimed at infectious dis-
ease specialists, which refers to a case of a pregnant woman
with a multidrug-resistant KPC-producing Klebsiella pneu-
moniae pyelonephritis [39]:
Which antimicrobial(s) would be appropriate for the
patient presented in the case?
A. Colistin (i.v.)
B. Oral fosfomycin
C. Oral fosfomycin and extended-infusion meropenem
D. Oral fosfomycin and extended-infusion cefepime
E. Ceftazidime-avibactam (i.v.)
F. Meropenem and ertapenem (i.v.)
The clinical image associated with this case is the genetic

typing of the KPC-producing Klebsiella cultured from this
patient, as compared with two more prevalent KPC-producing
Klebsiella isolates. A table with antimicrobial susceptibility
testing is also included. This case-based quiz provides a formi-
dable challenge even for an infectious disease specialist, and
is intended to improve care for patients with these devastating
infections [40]. Similarly, the tracheal stenosis case has an
important educational message for the generalist. Clinical
quizzes and images help to make these teaching points more
memorable, and the learning process more challenging and
enjoyable.
Table 8.3 compares the features of clinical images and
mystery image/clinical quiz articles. Regardless of the article
type, a clear and compelling image with a strong teaching
point has the best chance for publication.
Table 8.3 Comparison of clinical images and mystery image/clinical

quiz articles
Mystery image/clinical
Article type Clinical images quiz
Title Straightforward, Mysterious, ironic,
descriptive paradoxical
Image Archetypal images In general, same as
Selection of common diseases/ for clinical images
exam findings articles
Rare or atypical Diagnosable by many
presentations of or most generalist
common conditions physicians and some
Classic presentations trainees
of rare conditions Neither too obvious
Rare adverse effects nor too obscure
High educational High educational
value value
Combine different High clinical
media to enhance relevance
education (e.g., ECG Avoid: obscure and
and video of jugular clinically irrelevant
vein pulsations) cases, trivia without
High-quality images clear practical value,
with appropriate excessive technical
legends and arrows complexity (e.g.,
Avoid: foreign blots and gels, subtle
bodies, gross trauma, radiologic variants,
extreme rarity, electrophysiologic
poor-quality images, studies) unless aimed
implied criticism of at subspecialists
physician or patient
(continued)
References 117
Mystery image/clinical
Article type Clinical images quiz
Caption Generally 100450 Generally 3001500
words words
Includes brief case Brief case history
history, discussion only; discussion of
of pathophysiology, pathophysiology,
differential differential diagnosis,
diagnosis, treatment, etc., given separately,
clinical course, following answers
implications to multiple-choice
questions
Multiple- N/A Accessible to most
choice generalists
questions Subspecialty level
and answers, questions only if
with subspecialty journal
explanations Incorrect answers
explained
Clear justification
of correct answer(s),
followed by full
discussion
Teaching Essential Essential

point
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Chapter 9
How to Write a Clinical
Vignette Abstract
Jeffrey Wiese and Somnath Mookherjee
Introduction
Many professional medical conferences invite authors to

submit clinical vignette abstracts: brief case reports format-
ted as structured abstracts. These abstracts have strict word
limits that require efficient and precise prose. Submissions
are peer reviewed based on established criteria (Table 9.1).
The authors of accepted abstracts are invited to present post-
ers or give short oral presentations. This chapter presents 20
tips for writing an excellent clinical vignette abstract for
submission to a conference. Before and after examples are
used throughout to illustrate key points.

DOI 10.1007/978-3-319-41899-5_9
Table 9.1 Examples of criteria used for peer review of clinical vignette abstracts for three major internal medicine
122
conferences
Society of General Internal Medicine American College of Physicians Society of Hospital Medicine
(SGIM) [1] (ACP) [2] (SHM) [3]
Teaching value: Offers an important Significance: How significant Originality
diagnosis, physical examination, or or relevant are the abstract's Organization
management pearl conclusions in increasing Writing ability
Relevance to general internal medicine: understanding of a disease Relevance to hospital
Describes impact on clinical practice in process or in improving the medicine
internal medicine, teaching/education, or diagnosis or treatment of a
future research, places case in context disease state? How relevant is it
Overall assessment: Overall evidence of to the field of internal medicine?
scholarship, potential for publication Presentation: How logical are the
ideas presented in the abstract?
How interesting is the manner
of presentation? How clearly is
the content written and free of
significant grammatical errors?
Methods: If applicable, how
suitable is the design for the
stated objectives, and how
appropriate are any analysis
Chapter 9. How to Write a Clinical Vignette Abstract
techniques applied?
Introduction 123
Step 1: Just Tell the Story! Then Revise Using These

Tips .
First draft of the case description section of a clinical vignette

A 34 y/o male with hemophilia A with a history of IV drug use
and hepatitis C was admitted from clinic with fevers, shortness
of breath, dyspnea on exertion, and abdominal distension that
had been worsening for the past 2 months. The patient had been
crushing Dilaudid and injecting it every 6 h for the past 2 years.
On physical exam, he had a new 4/6 murmur consistent with
TR, JVD, a remarkably tense and distended abdomen that was
moderately tender, hepatosplenomegaly, and bilateral tender lower
extremity edema with a petechial rash from mid shin distal. Lungs
were clear, and no lymphadenopathy was appreciated. Chemistry
panel showed Na 139, K 4.7, Cl 100, Bicarb 25, BUN 8, Cr 0.98,
and glucose 107. AST was 20 U/L, ALT was 32 U/L. CBC showed
WBC count of 10, HCT of 32, and platelets of 165. INR, albumin,
and bilirubin were normal. ESR was elevated at 24. An abdominal
ultrasound showed an 18.7 cm liver, a 22.8 cm spleen, and minimal
ascites around the liver, and portal vein flow was hepatopedal. The
TTE and TEE showed no valvular masses or vegetations, severely
depressed RV systolic function and RV dilatation, severe tricuspid
regurg, and severe pulmonary hypertension.
The biggest barrier to writing a clinical vignette abstract is

getting the project started. Overcome this obstacle by imagin-
ing that you are telling a colleague about an interesting case,
and simply put the words on paper. Determine the abstract
headings for the conference to which you will be submitting
(Table 9.2), but do not yet worry about word limits or style
simply tell the story. The box above shows an excellent first
draft of the case description section of a typically struc-
tured clinical vignette abstract. By following these tips, this
draft can be transformed into an excellent submission.
124 Chapter 9. How to Write a Clinical Vignette Abstract
Tip 1
Write a great opening sentence: concisely introduce the
patient and the chief complaint. Include only the chief com-
plaint, but if there are two equally important symptoms, then
it is acceptable to include them both. The remaining symp-
toms can be listed with the associated symptoms, which
should follow in the next sentence. Do not include the past
medical history in the opening sentence.
Original
A 34 y/o male with hemophilia A with a history of IV drug
use and hepatitis C was admitted from clinic with fevers,
shortness of breath, dyspnea on exertion, and abdominal
distension that had been worsening for the past 2 months.
Revised
A 34-year-old man presented with 2 months of progressively
worsening shortness of breath and fever. He also noted
abdominal distension and dyspnea on exertion. His past
medical history included hemophilia A, intravenous drug use,
and hepatitis C.
Tip 2
Use an academic style of writing: pay attention to grammar,
syntax, and avoid the use of informal prose. Use man or
woman as a noun; use male or female (i.e., a female carpenter)
Table 9.2 Examples of clinical vignette abstract formats for three

major internal medicine conferences
Society of General American College Society of Hospital
Internal Medicine of Physicians Medicine (SHM)
(SGIM) 500 words (ACP) 450 words 3,000 characters
Title Title Title
Learning objectives Introduction
Case presentation Case presentation Case presentation
Discussion Discussion Discussion
Conclusions
Introduction 125
as adjectives. Do not use any informal abbreviations (y/o),

and write out all standard abbreviations on the first usage. Do
not use the brand names of drugs: for example, use hydro-
morphone rather than Dilaudid.
Tip 3
When possible, include the duration of the chief complaint as
a descriptor of the complaint (rather than adding to the end
of the sentence).
Tip 4
Omit the site of care unless it is unusual or important to the
case. For example, it is unnecessary to report that this patient
was admitted from clinic. On the other hand, include the site
of care when it is integral to the patients story: resuscitated in
the field, presented to a rural hospital in Botswana, etc.
Original
The patient had been crushing Dilaudid and injecting it every
6 h for the past 2 years.
Revised
Moved to the end of the case presentation: On further
questioning, he revealed that he had been crushing
hydromorphone (Dilaudid) and injecting it intravenously for
the past 2 years.
Tip 5
Do not release the highlight of the vignette too soon. It may
sometimes seem disingenuous not to present critical informa-
tion at the beginning of the vignette, especially if this informa-
tion was revealed relatively early during the actual clinical
encounter. However, as long as you are not altering the case
history, it is desirable to preserve some of the mystery for later
in the abstract. Delaying the punch-line makes the case much
more educational and engaging; so, the reader can ponder the
case much like the providers did when caring for the patient.
Original
On physical exam, he had a new 4/6 murmur consistent with
TR, JVD, a remarkably tense and distended abdomen that
was moderately tender, hepatosplenomegaly, and bilateral
tender lower extremity edema with a petechial rash from mid
shin distal. Lungs were clear, and no lymphadenopathy was
appreciated.
Revised
He had a four out of six murmur located at the apex that
increased in intensity with inspiration; neck veins were not
elevated. The abdomen was distended, and the liver and
spleen were enlarged. There was lower extremity edema and
a petechial rash on his shins.
Tip 6
Unlike in clinical documentation or oral case presentations,
not all section headings need to be announced. Save some
space by not stating the obvious. For example, it is unneces-
sary to state on physical exam. Rather, directly report the
key findings without introduction.
Tip 7
Report physical examination findings, NOT your interpreta-
tion of the findings. Rather than new 4/6 murmur consistent
with TR, describe what was actually observed, such as holo-
systolic murmur that increased with inspiration.
Tip 8
Avoid lengthy, run-on sentences. In the face of strict word limita-
tions, writers will often try to pack as much information as pos-
sible into a single sentence, hoping that this will somehow
decrease the word count. In actuality, this strategy usually results
in long, run-on sentences that are difficult to parse. A much bet-
ter strategy is to write short sentences that directly convey one
or two concepts, and omit all information that is not truly impor-
tant to the story. In the example above, the first draft has 46
Introduction 127
words (253 characters), and the rewritten version also has 46

words (but only 214 characters). When it does make sense to
group multiple concepts in a single paragraph, separate them
using semicolons, for example, the heart examination findings.
Tip 9
Include only the most relevant examination findings: deter-
mine the relevance by considering the likely differential diag-
nosis that is emerging from the story thus far. Include pertinent
negative findings. Consider including a set of vital signs but
this is not always necessary if they were unremarkable.
Tip 10
Report the physical examination as objective data: qualifiers
such as remarkably or essentially are uninterpretable to
the reader. What is remarkable to you may not be as remark-
able to others. Furthermore, using such adverbs adds an
unnecessarily dramatic element in a clinical case report.
Original
Chemistry panel showed Na 139, K 4.7, Cl 100, Bicarb 25,
BUN 8, Cr 0.98, and glucose 107. AST was 20 U/L, ALT was
32 U/L. CBC showed WBC count of 10, HCT of 32, and
platelets of 165. INR, albumin, and bilirubin were normal.
ESR was elevated at 24.
Revised
Basic metabolic panel, complete blood count, prothrombin
time, albumin, and bilirubin were normal.
Tip 11
This is not morning report. It is not necessary to provide
the initial laboratory panel unless the findings are relevant
to the case. If they are normal, that information may be
briefly stated. If lab values do need to be provided, be sure
to write out all abbreviations and provide units for all
measurements. Doing so typically adds significantly to the
word count; so, authors must be parsimonious in determin-

ing which labs are salient for the case.
Original
An abdominal ultrasound showed an 18.7 cm liver, a 22.8 cm
spleen, and minimal ascites around the liver, and portal
vein flow was hepato-pedal. The TTE and TEE showed no
valvular masses or vegetations, severely depressed RV systolic
function and RV dilatation, severe tricuspid regurg, and
severe pulmonary hypertension.
Revised
The liver was 19 centimeters (cm) and the spleen was 23 cm
by ultrasound. There were no valvular vegetations on the
transesophageal echocardiogram; the right ventricular
ejection fraction was depressed, and the right ventricle
was dilated. There was severe tricuspid regurgitation; the
estimated pulmonary pressure was _____. On further
questioning, he revealed that he had been crushing
hydromorphone (Dilaudid) and injecting it intravenously for
the past 2 years.
Tip 12
We are accustomed to stating that a test showed a certain

result; however, tests do not actually show things. It is bet-
ter to state the finding followed by the modality that revealed
the finding.
Tip 13
Do not include unnecessary information: it is tempting to be
comprehensive when reporting results, especially when there
are abnormal findings that may or may not have had signifi-
cance at the time the study was originally done. In a clinical
vignette abstract, however, it is necessary to discard findings
from lab or radiographic reports that ultimately prove to be
irrelevant or unimportant. For example, minimal ascites
around the liver could be omitted. Similarly, reporting mea-
surements or lab values to the greatest degree of accuracy
possible is seldom necessary. Round numbers that can be
Introduction 129
rounded without changing the meaning of the number: 18.7

is no more or less significant than 19, and the result
Tip 14
Report data that is important to the theme of the case. If
information that most clinicians would expect to have been
provided is clearly missing, then briefly explain why it was
not available. In this example, the estimated pulmonary pres-
sure would be important to report, if available.
Step 2: Write Good Learning Objectives
Even if the conference abstract format does not require the

submission of learning objectives alongside the abstract, it is
critical to determine the key points that were learned from
the case. These points will form the anchor for the discussion
and should be prominently featured in an oral or poster
presentation.
Tip 15
Consider the most important lessons that you learned from
the case: think about what a clinician should do when faced
with a similar clinical situation. Use this information to con-
struct the learning objectives.
Tip 16
Write the learning objectives as actions the reader will be
able to perform as a result of reading the case. Formulate
them as completing the sentence, After reading this case
report (or visiting this poster, or hearing this presentation)
the reader will be able to. Avoid the temptation to use
words such as know or understand when formulating
learning objectives. Objectives that begin with passive verbs
are weak and uninteresting compared to objectives that start
with more active verbs. Table 9.3 provides examples of strong
and weak learning objectives for this case.
Table 9.3 Examples of strong and weak learning objectives

Strong Weak
1. Recognize the clinical 1. Review the clinical
presentation of impurity-induced presentation of impurity-
pulmonary hypertension induced pulmonary
hypertension
2. Describe the pathophysiology 2. Understand the
of impurity-induced pulmonary pathophysiology of
hypertension impurity-induced pulmonary
hypertension
3. Determine the etiology of 3. Know the differential
fluid accumulation by mentally diagnosis of edema and ascites
tracing the flow of blood
backward from the aortic root
Step 3: Write a Focused Discussion
Original discussion
Cardiac complications of IV drug abuse are well known,
especially endocarditis. Less stressed in medical education
are the pulmonary complications from IV drugs use. Many
of these complications present as nonspecific complaints
consistent with interstitial lung disease. In IV drug users,
the microvasculature of the lung is particularly susceptible
to embolization by filtration of injected particulate
matter. This may occur when granular particles of drug or
impurities such as talc or starch are injected with the drug,
acting as foci for chronic granulomatous inflammatory
lesions. Subsequent fibrotic obliteration of the
parenchymal microvasculature results in angiothrombotic
pulmonary hypertension, and ultimately cor pulmonale
with right heart failure. The degree of disease is directly
related to the amount of material injected. Typical findings
upon imaging are diffuse symmetric pattern of interstitial
fibrosis either alone or with evidence of cor pulmonale.
Superimposed bacterial infections frequently complicate
the diagnosis.
Shortness of breath in an IV drug user should always
prompt the clinician to look for pulmonary complications,
such as fibrosis, regardless of the presence of infection.
Introduction 131
Revised discussion
Edema and ascites are problems commonly encountered
by the internist. A methodical approach to determining the
cause of the fluid accumulation is important in identifying
less common causes of this problem. One method is to
trace the flow of blood backward from the aortic root to
the site of the fluid accumulation. The point where fluid is
no longer accumulating is the site of the pathology. In our
patient with ascites, pulmonary hypertension and pulmonary
fibrosis were present with normal left heart findings. The
point of pathology was therefore the fibrosis in the lung with
precapillary obstruction causing pulmonary hypertension.
The microvasculature of the lung is the primary filter for
large particles from intravenous drugs. Embolic occlusions
of these vessels by injected drugs and foreign materials
like starch and talc act as foci for chronic granulomatous
inflammatory lesions. Progressive obliteration of the
microvasculature of the lung by fibrosis results in
angiothrombotic pulmonary hypertension and ultimately
right heart failure. The degree of disease is directly related to
the amount of material injected. The pathology predominates
in the middle and upper lung zones.
With the incidence of drug use on the rise, physicians
should be adept in identifying impurity-induced pulmonary
hypertension as a cause of right heart failure.
Tip 17
Establish the relevance of the case for the audience from the
very beginning. Case report authors already have a strong
sense that their case is important and should be shared ask
yourself why that is and explicitly state the answer at the
beginning of the discussion. Abstract reviewers are looking
for the most relevant cases (Table 9.1), and conference par-
ticipants will be most engaged by cases that are important in
their clinical practice.
Tip 18
Address each of the teaching points that were previously
determined. Discussions of esoteric pathophysiology and
in-depth literature reviews are not only prohibitively

lengthy, but will not be engaging to most time-limited read-
ers and reviewers.
Tip 19
Explain important concepts simply and without digression.
Imagine having a 1-minute window to explain the key points
from the case to a colleague. Rather than saying, In IV drug
users, the microvasculature of the lung is particularly suscep-
tible to embolization by filtration of injected particulate mat-
ter, it is more efficient and more likely to be remembered if
you say, The microvasculature of the lung is the primary
filter for large particles from intravenous drugs.
Tip 20
End with a moral of the story that highlights the relevance
of the case and reinforces one of the major teaching points.
Conclusion
Submitting a clinical vignette can be a valuable experience. It
is an ideal opportunity for trainees and faculty to work
closely together on a scholarly project. Many conferences
offer competitive awards for the best clinical vignettes oral
or poster presentations, providing an avenue for recognition
by peers and leaders. For those in academic medicine, pre-
senting an abstract may allow access to travel funds and bol-
ster a curriculum vitae. Finally, writing and submitting a
clinical vignette abstract is a great first step to publishing a
full case report. Follow the tips listed above to start the writ-
ing project with a concise, brief report of the case, setting the
stage for a subsequent manuscript. Chapters 7, 8, and 10 pro-
vide further guidance on writing full case reports for
publication.
References 133
References
1. Newsom J, Estrada CA, Panisko D, Willett L. Selecting the best
clinical vignettes for academic meetings: should the scoring tool
criteria be modified? J Gen Intern Med. 2012;27(2):2026.
2. Guidelines for Submissions of Abstracts [Website]. American
College of Physicians. Available from: https://www.acponline.org/
membership/residents/competitions-awards/acp-national-
abstract-competition. Accessed 2 May 2016.
3. Guidelines for Submissions of Abstracts [Website]. Society of
Hospital Medicine. Available from: http://www.hospitalmedicine.
org/Web/Education/Academic___Research/Academic_
Research_Community/Abstract_Submission.aspx. Accessed 2
May 2016.
Chapter 10
How to Write a Clinical
Problem Solving Manuscript
Gurpreet Dhaliwal and Gabrielle N. Berger
Introduction
A clinical problem solving (CPS) exercise highlights the pro-

cess by which an experienced clinician approaches a diagnos-
tic puzzle. It is constructed in a manner that emphasizes
thought process and reasoning as the case unfolds. A CPS
manuscript is a variation on the traditional case report which
allows the authors to explore a clinical dilemma in greater
detail and present a broader set of teaching points. Writing a
CPS manuscript requires a larger investment of time and
energy than a traditional case report or clinical image. A CPS
project will enhance the authors understanding of clinical
reasoning while advancing their medical knowledge. CPS
manuscripts are often published in high-impact journals.
This chapter is a step-by-step guide to writing a successful
CPS manuscript.
Selecting the Case

Characteristics of a suitable case for a CPS manuscript can be
summarized by the TEACH acronym (courtesy of Sanjay
Saint MD MPH):
Teaching points can be made
Enigma the diagnosis must be a challenge

DOI 10.1007/978-3-319-41899-5_10
136 Chapter 10. How to Write a Clinical Problem Solving
Answer must be established by a gold standard test

Cool (interesting) case readers should say wow at
the end
Honest authors cannot change the facts of the case
Among these, the most important criterion is that the

expert discussant must be able to make meaningful teaching
points that are relevant to a generalist audience; no other
aspect of the case can overcome a deficit in this area.
The Planning Stage

Once the primary author identifies a clinical case, it is impor-
tant to invite a faculty mentor who has coauthored a CPS
case previously to participate in the project. This person will
often become an active collaborator and coauthor, although
neither is assumed. This mentor is rarely the faculty member
on the primary team or the consulting service; rather, the
primary author should look for someone who understands
the process of writing a clinical problem solving case, not the
details of the case itself.
The authors should contemplate the discussion section of
the paper before focusing on the presentation of the case.
How will you engage the audience after they have read the
case? What topic will you highlight in addition to the final
diagnosis? This may include a theme about clinical reasoning,
changes in the practice of medicine, or reaffirmation of a
principle (e.g., the importance of the social history). Without
a narrative to engage the reader, the commentary section is
likely to fall flat. Esoteric teaching points about rare diseases
are of limited interest to most readers.
Authors should determine whether the case has already
been published in any format, or if other providers (e.g., a
specialty service) intend to do so. Prior dissemination as a
poster, abstract, or oral presentation at a medical conference
does not preclude publication in most journals, but such pre-
sentation should be noted in the acknowledgment section. If
the case has been disseminated in any other print or elec-
The Planning Stage 137
tronic format, it may be difficult to publish as a CPS manu-

script on account of duplicate publication policies. These
issues are best discussed with the target journal series editor
before embarking on the project.
Journals encourage the inclusion of images that enhance
the readers experience and the visual appearance of the
article. Think about what images capture the key data the
treating physicians contended with. Common images are
rashes, surgical specimens, histopathology, radiology, or an
EKG. These visual representations of the case substantially
enhance the manuscript by engaging the audience and bring-
ing the case to life. Although procuring or interpreting images
may require assistance from a colleague, beware when this
assistance is provided only on the condition of authorship.
Such assistance is grounds for acknowledgment, not
authorship.
Choose a target journal and review author instructions
early. Journals that regularly publish CPS manuscripts include
the New England Journal of Medicine (NEJM), Journal of
General Internal Medicine (JGIM), and Journal of Hospital
Medicine (JHM). Journal-specific instructions provide valu-
able information on authorship guidelines, formatting, and
word limits. Authors should send a pre-submission inquiry to
the series editor of the target journal that includes a brief
summary of the case, the diagnosis, and anticipated teaching
points. The editor may encourage submission or advise that
the case is not suitable (e.g., insufficient clinical dilemma or
similar case already in progress). This inquiry can save valu-
able time and allow the authors to redirect their efforts
toward a different journal where publication is more likely.
Finally, do not invite coauthors (other than the faculty
mentor) in the planning phase. The primary author will even-
tually invite coauthors, but after one or two people are
involved, there is rarely enough work to go around in the
early stages. It is not fair to invite colleagues when there are
no available tasks that qualify them for authorship. A useful
rule of thumb is the likelihood of completion is inversely
related to the number of early authors. See authorship guide
below for more details.
Constructing the Case Protocol
After selecting a faculty mentor, clarifying the key teaching

points and themes, identifying a target journal, and collecting
images, the primary author should start constructing the case
protocol.
The case protocol (see Table 10.1 for definitions) is the
text and images that will be presented to the discussant. Once
Table 10.1 Glossary of terms used in this chapter

Terminology Definition
Case The complete narrative of the case that will be
protocol presented to the discussant.
Aliquot A section of the case protocol. After the case
protocol is written, it is divided into aliquots,
each of which is presented sequentially to the
discussant. A case protocol is typically divided
into 68 aliquots.
Discussant The discussants analysis of the information
response presented in the preceding aliquot.
Case The entire exchange between author and
discussion discussant. The case discussion consists of the
aliquots with interspersed sequential discussant
responses.
Commentary The section of the manuscript that summarizes the
case, explores the clinical dilemmas, and reviews
relevant diseases or clinical reasoning principles.
Clinical A section required by some journals (e.g.,
reasoning Journal of General Internal Medicine) that is
analysis integrated into the case discussion and follows
most discussant responses. The clinical reasoning
analysis section provides commentary on the
diagnostic reasoning process.
Teaching A section at the end of the manuscript required
points by some journals (e.g., Journal of Hospital
Medicine) consisting of 35 bulleted clinical
teaching points.
Constructing the Case Discussion 139
completed, the protocol should be divided into six to eight

sections (aliquots). Each aliquot should provide the discus-
sant with enough information to modify their differential
diagnosis from the section before. The first aliquot usually
starts with the chief complaint and history of present illness
(HPI). The second aliquot often reveals the past medical his-
tory (PMH) and medications with relevant health-related
behaviors. Sequential aliquots outline the physical examina-
tion, then labs and imaging, then clinical course, then more
clinical course, then final clinical event, and then gold stan-
dard test result.
The primary author should review and edit the protocol
with the faculty mentor for clarity and accuracy before send-
ing it to the discussant. The medical details of the case must
be accurate as the case will become part of the scientific
record.
Constructing the Case Discussion

After finalizing the case protocol, the first author and faculty
mentor should identify a clinical discussant to invite as a
coauthor. This person should not know the case in advance.
Such knowledge makes the case discussion less authentic and
violates the spirit of the exercise, which is predicated on
extemporaneous thinking. Select a clinician who can discuss
a broad range of medical topics, not an expert in the final
diagnosis. It is the journey to the final diagnosis not the
diagnosis itself that makes for an educational discussion.
The invited discussant should have a reputation for timeli-
ness and a track record of following through on projects. The
first author may even consider including a timeline in the
invitation such as the period of time (e.g., within 2 weeks) in
which a response from the discussant would be appreciated
for each aliquot.
Send the first aliquot to the discussant. The discussant
response should be two to four paragraphs. Following the dis-
cussant response, paste aliquot 2 (but no additional aliquots)
into the same document and return the updated document
to the discussant. Repeat this process for all subsequent ali-

quots. With each new aliquot the primary author may direct
the discussant to address specific issues, such as please
elaborate on the initial differential diagnosis here, or what
conditions are you most concerned about? but should not
provide hints.
Give the discussant a warning when the next-to-last ali-
quot is being presented so he/she will commit to a leading
diagnosis in their response. A discussant response to the
final aliquot (where the diagnosis is disclosed) is optional.
The resulting document is the first draft of the case
discussion.
Writing the Manuscript

The primary author (often assisted by a coauthor) should edit
the first draft of the case discussion to generate a concise nar-
rative that flows easily from one aliquot to the next while
highlighting the discussants clinical problem solving skills.
The editing author may decide to merge two aliquots and
their respective discussant responses if this helps achieve a
succinct case presentation with clear teaching points. (See the
example below for excerpts from a case discussion in a CPS
manuscript published in the New England Journal of
Medicine) [1].
Once the case discussion has been edited, the first author
should draft the commentary section (typically 500700
words). It should briefly summarize the case, review the rel-
evant diseases and dilemmas, and highlight general themes
and takeaway points. After review by the faculty mentor, it is
often helpful to invite a disease or domain expert who can
review the clinical discussion and commentary and add
teaching points. This person, typically a middle author, will be
a valuable resource when specialty-level inquiries come from
the editors and reviewers.
Excerpts from a Case Discussion 141
Excerpts from a Case Discussion
This is the first aliquot of a CPS, followed by the

discussants response. The aliquot is brief, provid-
ing enough information for the discussant to for-
mulate an initial approach to the patient without
overwhelming the reader or discussant with too
much data.
A 22-year-old woman presented to the emergency

department with a 4-week history of cough, progressive
shortness of breath, subjective fevers, and malaise. On
the day of admission, she was unable to walk farther
than one city block without stopping to rest. She also
noted new swelling in both legs.
This patients progressive dyspnea may be due to
volume overload, primary pulmonary processes, or ane-
mia. The combination of dyspnea and lower-extremity
edema suggests volume overload, typically explained by
cardiac, hepatic, or renal failure. The duration of the
reported problems and the association with systemic
symptoms suggest an inflammatory, infectious, or malig-
nant cause.
This is the second aliquot followed by the discus-

sants response. This aliquot provides more infor-
mation about the patients presenting symptoms
and history. The discussant now formulates a more
detailed differential diagnosis, supporting his clini-
cal reasoning with brief statements about the
patients risk factors and clinical associations.
The patient reported having arthralgias in her hands

and knees that had begun 3 months before admission
and were worse in the morning. Her medical history
included migraine headaches since she was 10 years
of age and subclinical herpes simplex virus type 2
infection. Three years earlier, she had undergone an
uncomplicated delivery of a healthy baby at 40 weeks
gestation; she reported no other pregnancies. She was
taking no prescription medications. Originally from El
Salvador, she had immigrated to the United States 5
years earlier but had not traveled recently. She worked
in food services. She did not smoke cigarettes or use
illicit drugs and rarely consumed alcohol. A sister in El
Salvador had received a diagnosis of kidney disease of
uncertain cause. The patient did not have patchy alope-
cia, aphthous ulcerations, dry eyes, dry mouth, rashes, or
Raynauds phenomenon.
Rheumatoid arthritis could explain subacute symmet-
ric arthralgias in a young woman, but severe pulmonary
or cardiac manifestations early in the disease course
would be unusual. Systemic lupus erythematosus (SLE)
with renal involvement could account for the arthralgias
and volume overload. Sarcoidosis can cause arthralgias
with pulmonary or cardiac involvement. Patients with
dermatomyositis or polymyositis may present with early
interstitial lung disease and concomitant arthritis.
Subacute bacterial endocarditis could also explain this
constellation of symptoms.The patients Central American
origin raises the possibility of Chagas cardiomyopathy.
Other infectious causes to consider include tuberculosis
and infection with endemic fungi, such as histoplasmosis
or paracoccidioidomycosis. The history of kidney disease
in her sister raises the question of hereditary renal condi-
tions, such as Alports disease or polycystic kidney disease,
although they do not cause arthralgias; there could also be
a shared predisposition to multisystem disease that affects
the kidney (e.g., SLE). Thyroid disease (hyperfunction or
hypofunction) should also be considered as a cause of at
least some of her presenting symptoms.
Excerpts from a Case Discussion 143
a b
Figure 10.1 Findings on Transthoracic Echocardiography at

the Time of Presentation. The parasternal long-axis view in
Panel A shows a complex mass of soft tissue infiltrating the pos-
terior wall of the left ventricle and encasing the posterior mitral-
valve leaflet (arrow). The apical four-chamber view in Panel B
shows encasement of the posterior mitral-valve leaflet by the
soft-tissue mass (arrow) and involvement of the anterior mitral-
valve leaflet. The mean diastolic mitral-valve pressure gradient
of 16 mm Hg, shown on continuous-wave Doppler imaging in
Panel C (arrow), is consistent with severe mitral stenosis
This is the eighth aliquot followed by the discus-

sants response and accompanied by an image. At
this point, the discussant is evaluating very specific
hypotheses in detail.
A transthoracic echocardiogram showed a large, irreg-

ular mass encasing the posterior leaflet of the mitral valve
and resulting in severely reduced leaflet mobility (Fig. 10.1;
Figure 10.2 Findings on magnetic resonance imaging at pre-

sentation. A transverse cardiac image obtained without the
administration of gadolinium shows a mass extending into the
left atrium and left ventricle (arrow)
and available with the full text of this article at NEJM.

org). There was severe leaflet thickening, with a mean
diastolic transmitral gradient of 16 mm Hg. The pulmo-
nary artery systolic pressure was 67 mm Hg. The mass
extended into the basal posterior and inferior walls of the
left ventricle and the posterior wall of the left atrium. Left
ventricular function and right ventricular function were
normal. Transesophageal echocardiography and cardiac
magnetic resonance imaging (Fig. 10.2) confirmed these
findings and showed involvement of the anterior leaflet
and chordae tendineae, along with extensive spread into
the atrioventricular groove.
This large, infiltrative mass may be causing heart fail-
ure due to valvular involvement, hemodynamic obstruc-
tion, or both. In addition, it is probably the source of the
embolic phenomena (e.g., splinter hemorrhages). The
encasement of the mitral valve is causing severe mitral
stenosis and accounts for both the apical diastolic
murmur and the dyspnea on exertion.
Journals with Additional Emphasis on Clinical Reasoning 145
The most common intracardiac tumor is atrial myx-

oma, which frequently causes emboli and striking
immunologic phenomena. However, myxomas are typi-
cally pedunculated and mobile. In this case, the degree
of invasiveness and adherence is more characteristic of
a primary cardiac tumor, such as rhabdomyosarcoma
or angiomyosarcoma, or a metastasis. The patients
presentation is otherwise suggestive of SLE, but the
large size of the mass is not typical for LibmanSacks
endocarditis. It is plausible that her employment in
food services may put her at risk for a culture-negative
endocarditis (e.g., brucellosis or Q fever), but signs of
infection, such as fever, are absent. Although bland
thrombus due to the antiphospholipid syndrome or the
nephrotic syndrome is a consideration, invasiveness and
valvular encasement are not characteristic of thrombus.
Journals with Additional Emphasis

on Clinical Reasoning
There are two requirements that are specific to the Journal of
General Internal Medicine Exercises in Clinical Reasoning
series (JGIM ECR). This format requires a clinical reasoning
analysis section that follows most of the discussant responses,
so that the case discussion is a repeating series of case aliquot
case discussionclinical reasoning analysis segments. A third
author with expertise in clinical reasoning is often required for
this analysis and will usually be a middle author on the paper.
This section is typically constructed after the case discussion is
completed, because it allows the clinical reasoning author to
observe the arc of the case and discussant comments to deter-
mine which theme(s) warrant emphasis. JGIM ECR also dif-
fers from other journals in that the commentary section is
focused entirely on additional clinical reasoning analysis of the
case; didactic medical facts are deferred to bulleted teaching
points, which conclude the manuscript (see the example below
for excerpts from an Exercises in Clinical Reasoning article
published by Journal of General Internal Medicine) [2]:
This is the first aliquot of an Exercise in Clinical

Reasoning article from Journal of General Internal
Medicine, followed by the discussants response
and a clinical reasoning analysis section. Similar
to the NEJM format, the initial aliquot allows the
discussant to formulate an initial approach to the
patient. The diagnostic reasoning section provides
additional commentary to describe the discus-
sants thought process and teach clinical reasoning
concepts.
Clinical Information: A 43-year-old Mexican woman pre-

sented to the emergency department with abdominal pain.
Her illness had begun 1 week earlier with fevers to 38.9 F
and intermittent frontal headache without photophobia or
other neurological symptoms. Two days prior to presenta-
tion, she began having left upper quadrant (LUQ) abdom-
inal pain described as sharp, unremitting, and radiating to
the midepigastrium, right upper quadrant, and left flank.
The pain did not change with eating, but she did report
episodic nausea and vomiting. She denied hematemesis,
dysuria, or diarrhea. Her last menstrual period had begun
3 weeks earlier, and she denied recent sexual activity. One
day prior she had been diagnosed with gallstones at
another emergency department and treated with oral
metoclopramide and hydrocodone-acetaminophen.
Clinician. Left upper quadrant pain commonly results

from gastritis, colitis (splenic flexure), pancreatitis,
pyelonephritis, nephrolithiasis, splenic enlargement or
infarction, or left lower lobe pneumonia. Intermittent
headaches frequently accompany systemic illness, so the
challenge is determining if the associated fever signals
Journals with Additional Emphasis on Clinical Reasoning 147
an intracranial infectious process such as meningitis,

encephalitis, or brain abscess. The severity and duration
of headache, lack of previous headache history, presence
of meningeal signs, and neurological deficits are
common indications for imaging the central nervous
system and analyzing the CSF.
Diagnostic Reasoning. The problem representation is an

abstract one-sentence summary that elaborates the key
features of the case. It triggers plausible diagnostic
hypotheses and directs exploration of further historical
elements, physical examination features and diagnostic
testing. In complex cases it is often necessary to consider
more than one problem representation. Here the competing
versions might be: (1) a 43-year-old woman of reproductive
age with a subacute febrile illness and headaches associated
with LUQ abdominal pain, nausea, and vomiting; or (2) a
43-year-old woman of reproductive age with acute onset of
sharp, unremitting LUQ pain, nausea, and vomiting. Using
the first problem representation, the clinician would likely
consider serious intracranial infections and mass lesions.
In the second problem representation, the LUQ pain is the
focal point that directs further data gathering. It is often
useful to explore competing problem representations to
avoid premature closure. Premature closure is the failure
to consider other plausible diagnoses after an initial
working diagnosis is reached. It is one of the most common
clinical reasoning errors made by clinicians.
A clinical teaching points section concludes the

article, summarizing the key take-home points
from the case. It includes teaching points on the
specific disease process (brucellosis), the differen-
tial diagnosis (granulomatous hepatitis), and the
importance of the social history.
Clinical Teaching Points

1. Human brucellosis is a very common illness world-
wide. Four brucella species melitensis, suis, abortus,
and canis cause the majority of human illness, with
B. melitensis being the most common.6
2. Brucellosis is generally transmitted by direct contact
with infected animals (cattle, sheep, goats, or pigs) or
by consuming unpasteurized dairy products. The
incubation period is days to months.
3. Though brucellosis can involve any organ system, it
usually presents with nonspecific symptoms, includ-
ing undulating fevers, night sweats, malaise, weight
loss, and arthralgias. It can also present with focal
brucellosis syndromes, including meningitis, arthritis,
endocarditis, or epididymo-orchitis.
4. Granulomatous hepatitis is caused by infections (e.g.,
tuberculosis, histoplasmosis, coccidioidomycosis, Q
fever, brucellosis, syphilis, cryptococcosis, leprosy),
drugs, malignancy (e.g., lymphomas, renal cell carci-
noma), or autoimmune diseases (e.g., sarcoidosis, poly-
myalgia rheumatica, primary biliary cirrhosis). Up to
20 percent of cases are idiopathic.7
5. The social history is often a key discriminating feature
in febrile illnesses, particularly for patients who travel
outside of industrialized areas. They are often exposed
to infections that are not routinely considered.
Final Steps
There are a number of final steps in preparing the manuscript
for publication including:
Formatting images (e.g., adding arrows if necessary)
Drafting image legends
Drafting the teaching points section
Guide to Authorship 149
Adding references
Determining a title
The best title makes a clever but obtuse reference to the
teaching points, the manner in which the case unfolds, or the
final diagnosis. For instance, The Right Angle was chosen as
a title for a case of constrictive pericarditis that evaded detec-
tion because the extreme elevation in jugular venous pressure
was difficult to appreciate when the patient was at the typical
45 of recumbency; the right angle of 90 (seated position)
would have facilitated detection.
Involve the entire authorship group in multiple rounds of
editing to produce a succinct and engaging manuscript.
Before submitting the manuscript, carefully check the author
instructions again. Failure to follow author instructions is a
common reason for immediate manuscript rejection.
Guide to Authorship
The maximum number of authors on a CPS manuscript is
typically five or six. While there is no standard approach to
authorship, consider the following framework as a guide:
First author: this is the person who initiated the project and
remains the leader throughout. The first author drafts
most of the case protocol and parts of the commentary,
coordinates the contributions of other coauthors, leads
the submission process, and serves as the corresponding
author with the journal.
Middle authors: these collaborators should be listed in
descending order according to the amount of work
contributed and stage of involvement in the project.
Middle authors typically include the discussant, the clini-
cal reasoning expert (if one is involved), and a disease/
domain expert.
Final author: this person is often the coordinating faculty
advisor for the project who made multiple contributions
through the project such as helping the first author
identify other collaborators, editing the case discussion

and commentary, and providing substantial input into
the final editing and submission process.
It is equally important to understand what types of contri-
butions do not qualify for authorship:
I made the diagnosis
I took care of the patient
I was on the team
I was the consultant
I was the attending
I am the primary care provider
I interpreted the image
The guiding principle is that caring for the patient does

not equal scholarship. Rather, authorship is reserved for
people who contribute substantially to the creation of the
manuscript.
Conclusion
Taking a case from the medical record to a CPS manuscript
requires tenacity, leadership, and collaboration. This process
is rewarding because it offers the opportunity to simultane-
ously enhance medical knowledge and clinical reasoning, just
like we strive for in our daily practice and teaching.
References
1. Tarter L, Yazdany J, Moyers B, Barnett C, Dhaliwal G. The Heart
of the Matter. N Engl J Med. 2013;368(10):94450. doi:10.1056/
NEJMcps1114207.
2. Keenan CR, Dhaliwal G, Henderson MC, Bowen JL. A 43-year-
old woman with abdominal pain and fever. J Gen Intern Med.
2010;25(8):8747. doi:10.1007/s11606-010-1372-3.
Chapter 11
Submitting a Case Report
Manuscript
Gabrielle N. Berger and Somnath Mookherjee
Introduction
Publishing a case report requires thoughtful selection of an

appropriate journal. Historically, case reports were fixtures of
many prominent journals. However, this practice has declined
significantly over the last several decades as the rise of
evidence-based medicine led journals to focus more closely
on their impact factor, a measure of the journals competi-
tiveness and relevance to the field [1]. In this competitive
environment, most traditional journal editors publish only
the case reports they feel will resonate most strongly with
their audience. In this chapter, we present guidance to help
authors successfully navigate the submission process.
Defining the Target Audience

The most important first step in selecting a journal for a case
report submission is to identify the target audience. Some case
reports may be of interest to a generalist audience while oth-
ers may be more suited for subspecialists or even nonphysi-
cian health professionals such as pharmacists and nurses.

DOI 10.1007/978-3-319-41899-5_11
152 Chapter 11. Submitting a Case Report Manuscript
When deciding on the target audience, consider the

following:
What are the take-home points of the case report? Who is
most likely to incorporate these take-home points into
their daily practice?
If the case report focuses on an unusual presentation, who
is most likely to see the patient a primary care physician,
an emergency department physician, a surgeon, a hospitalist,
a subspecialist?
If the case report focuses on treatment, who is most likely
to be administering that therapy?
Narrow the search for the most appropriate journals by
taking time to define the anticipated audience as clearly as
possible. Consider targeting subspecialty audiences even if
you have a generalist practice, such as internal medicine,
pediatrics, or general surgery. Subspecialty journals may be
particularly interested in publishing case reports of rare
presentations or unexpected side effects of a treatment
that affect their specific patient populations. Furthermore,
some specialty journals publish many more case reports
than generalist journals. For example, a recent issue of the
Annals of Thoracic Surgery published no less than 21 case
reports [3]. While the majority of the authors were cardio-
thoracic surgeons or cardiologists, other specialties repre-
sented among the authorship included anesthesiology,
radiology, radiation oncology, pulmonary medicine, inten-
sive care medicine, neurosurgery, maternal fetal medicine,
obstetrics and gynecology, pathology, hematology, and
oncology.
When considering submission to a subspecialty journal, it is
helpful to request that a colleague in that subspecialty review
the case to ensure it will be a good fit for the journal under
consideration. If so, you may wish to invite them to be a co-
author to review the submission for clarity, focus, relevance, and
accuracy. This co-author may prove particularly helpful in field-
ing inquiries that come from the editors and other readers.
Selecting a Journal and Format 153
Selecting a Journal and Format
After considering the target audience, identify the journals

in that field with a track record of publishing case reports.
Some journals publish case reports in every issue, while oth-
ers have a recurring (e.g., quarterly) segment devoted to case
reports. Before submitting, review recent case reports pub-
lished by the target journal to ensure the submission reso-
nates with the topics, tone, and format of cases previously
published in that journal. If there is any doubt about the
appropriateness of the submission, send an inquiry to the
journals editor prior to submitting. A journal that does not
regularly publish case reports may be more likely to do so if
the clinical conundrum or syndrome being reported piques
the editors interest.
When submitting a research manuscript, authors com-
monly aim for journals with a high-impact factor to augment
their CV and enhance opportunities for career promotion.
While it is valuable to be aware of a journals impact factor
when submitting a case report, it is more important to iden-
tify journals that have a history of publishing this type of
work. Submitting to journals that do not accept case reports
or only publish case reports from major institutions (such as
the Centers for Disease Control or the National Institutes of
Health) is unlikely to result in a satisfying outcome for the
authors and will delay eventual publication.
Many journals have developed unique variations of the
traditional case reports in order to be more interesting and
relevant to their readership. Clinical challenge cases, mystery
cases, novel therapeutic strategies, images in clinical medi-
cine, clinical reasoning papers, and clinical vignettes can all be
considered to fall under the general description of case
reports, but have varying formats. Review the various case-
reporting options in the journals under consideration to
determine the best fit for your case. At the same time, con-
sider the amount of time that you can invest in putting the
manuscript together. Clinical problem-solving papers require

the most time (see Chap. 10). Clinical images take much less
time and may better highlight the teaching point of your case.
Predatory Publishers
Avoid falling prey to predatory publishers. These are compa-
nies and individuals that charge authors large sums to publish
their work, often in non-peer-reviewed journals or online
forums [4]. In the era of open access information, there has
been a proliferation of these types of publications; they are
rarely subjected to quality control processes, often are not
recognized by academic promotions committees, and publi-
cations are rarely listed in reputable databases. Charges for
publication can range from as little as $25.00 to as high as a
staggering $3,000.00. Authors eager for publication should
resist the temptation to engage with these groups and focus
instead on respected, peer-reviewed outlets.
An increasing number of journals are devoted entirely to
publishing case reports. While some of these journals adhere
to the accepted peer-review process, many do not. Before
submitting to a case report journal, verify whether it is
indexed on PubMed and whether it is affiliated with an estab-
lished subspecialty publication.
Submitting a Case Report Manuscript

After choosing the target journal and determining the format
for your case, closely review the journals guidelines for sub-
mission [5]. This can be done by visiting the journals website
and reading the information listed under author instructions.
Verify that your case meets the journals criteria for consider-
ation: some journals will only accept submissions that report
novel syndromes or disease processes being reported for the
first time. Other journals have more liberal criteria, publishing
case reports as long as they are educational in some way. Pay
Conclusion 155
particular attention to the journals requirements on patient

consent and permission for use of images. There is usually a
limit to the number of authors allowed on a case report; note
that a submission may be rejected simply because there are
too many authors. When submitting, clearly identify the cor-
responding author. This is the person whom the journal edi-
tors will contact for additional information and clarification
on the manuscript. It is not uncommon for a journals editorial
board to engage in multiple rounds of editing with the corre-
sponding author prior to accepting the manuscript (See Chap.
12 for strategies for responding to peer review).
Be sure to strictly adhere to the journals guidelines
regarding word count and formatting. A manuscript that is
not formatted correctly, has spelling or other grammatical
errors, or is too long is likely to be rejected without further
consideration. Some case report manuscripts may need to
be reformatted to fit the section requirements for a par-
ticular journal; this work should be done thoughtfully and
prior to submission to increase the likelihood of accep-
tance. Finally, note whether the journal requires inclusion
of an abstract.
Conclusion
Selecting an appropriate journal for submission is a critical
step toward having a case report published in the medical
literature. Cast a wide net when considering what types of
journals and audiences would be most interested in the clini-
cal question addressed in the case report. Have an open mind
when considering the most appropriate format for your sub-
mission, balancing what best fits your case and the time you
have to invest in the project. Additionally, consider inviting a
subspecialty collaborator to make the submission more
appealing to subspecialty audiences. Approach the submis-
sion process thoughtfully and with a plan for adapting the
manuscript as needed to help lay the groundwork for a suc-
cessful outcome.
References
1. Thompson PJ, Bs M. How to choose the right journal for your
manuscript*. Chest. 2007;132:10736. doi:10.1378/chest.07-1340.
2. Warner JO. Case reportswhat is their value? Pediatr Allergy
Immunol. 2005;16(2):934. doi:10.1111/j.1399-3038.2005.00266.x.
3. Oliemy A, Mahesh B, Pathi V. Acute traumatic right to left car-
diac shunt. Ann Thorac Surg. 2016. doi:10.1016/j.
athoracsur.2016.02.080.
4. Beall J. Best practices for scholarly authors in the age of preda-
tory journals. Ann R Coll Surg Engl. 2016;98(2):779. doi:10.1308/
rcsann.2016.0056.
5. McCarthy LH, Reilly KEH. How to write a case report. Fam
Med. 2000. doi:10.1136/bmj.327.7424.s153-a.
Chapter 12
The View from the Journal
Somnath Mookherjee and Brian J. Harte
Introduction
Writing a manuscript is a long, arduous process. At some
point, the lead author must decide that the work is finished,
and prepare to submit it. The first part of this chapter pro-
vides a final checklist to review before proceeding with sub-
mission. Even if the guidance offered in Chaps. 7, 8, and 10 is
closely followed while writing the case report, the final
version of the manuscript could almost certainly use a little
more polish to maximize the chances of acceptance.
While it may feel like the end of a lengthy process, submit-
ting a case report to a journal is usually the beginning of
another long journey. Peer review can take months, and
responding to peer review can be equally time consuming.
Papers often go back and forth between the journal and the
authors several times before finally being accepted for publi-
cation. The second part of this chapter provides practical
guidance to make this process as smooth as possible.
Presubmission Checklist
1. Read the submission guidelines from the journal again!
Make sure that the submission is in compliance with all the
journals requirements. Even though this was presumably

DOI 10.1007/978-3-319-41899-5_12
158 Chapter 12. The View from the Journal
done prior to creating the manuscript, there are several

reasons to verify the guidelines prior to submitting:
Guidelines may have changed from when the paper was

started many months have passed.
Double-check the word limits and word counts in the
final draft. Otherwise, the automated submission system
may reject the paper due to length, requiring last-
minute edits and deletions to permit the paper to be
submitted.
Trying to shoehorn in a submission NEVER works. For
example, if the journal guidelines say that case reports
can only be submitted as letters to the editor, trying to
sneak it into the journal as a full report will not be
successful.
2. Re-read the manuscript from the perspective of the journals

readership. Case reports may be submitted to several jour-
nals before finally being accepted. Verify that the content
and teaching points are targeted to the appropriate audi-
ence with the original submission and with any resubmis-
sion. Editors and reviewers greatly appreciate it when
authors have made the effort to create a case report that is
relevant and informative for their readers. As discussed in
Chap. 11, it is often fruitful to submit case reports to sub-
specialty journals. A specialized audience is much different
than a generalist audience, and unless the manuscript is
adjusted accordingly, it will almost certainly be immedi-
ately rejected, no matter how interesting the case.
3. Sweep the manuscript for any (accidental) plagiarism.

Plagiarism is surprisingly common: a recent systematic
review showed that 1.7 % of scientists admitted to having
committed plagiarism at least once, and 30 % reported that
they knew of at least one colleague committing plagiarism-
related behaviors [1]. One journal reported that 12 % of
their medical case report submissions were rejected due to
plagiarism [2]. Revisit the manuscript and make sure that
all of the prose is original. A common inadvertent source of
Presubmission Checklist 159
plagiarism is initially outlining parts of a manuscript with

elements cut and pasted from other sources. Authors plan
on rewriting and citing sources later, but with successive
drafts, these elements may unintentionally become inte-
grated into the manuscript. If unsure whether a particular
turn of phrase was original or copied, try searching for it by
pasting into a standard Internet search engine. Limited
online plagiarism-check services are also freely available.
Journals use more sophisticated plagiarism screeners to
detect previously published material. It is critical to elimi-
nate any borrowed material before submitting the article.
Plagiarism, even if inadvertent, is a major publishing and
academic offense. If the journals editorial team discovers
evidence of plagiarism, the consequences can be severe.
4. Re-read for clarity and flow. Poor writing repeatedly

emerges as a major reason why journal editors reject
papers [3]. This is a disconcerting fact. After all, an immense
amount of effort is expended on putting the manuscript
together. By the time it is submitted, the manuscript has
survived ruthless editing, wordsmithing, and rearranging of
sentences and paragraphs. Every change has been tracked,
accepted or rejected, and commented upon. As a conse-
quence, the manuscript probably has a certain logic and
organization to the authors, but consider how it would read
to someone who picks it up for the first time. What may
look like a perfectly crafted, albeit lengthy, sentence to an
author, with three semicolons and five commas, is more
likely an unintelligible quagmire to a reader who has not
had 3 months to parse it. Upon this final re-reading, if sec-
tions emerge that might benefit from revision do not sub-
mit the paper. It is much preferred to take the time to give
a final polish for clarity and flow rather than submitting
something that still does not read well. Here are four quick
tips to optimize the paper for clarity and flow:
Examine the structure of each paragraph, especially in
the discussion. The majority of paragraphs should be in
a traditional format: topic sentence, body sentences
(3-4) supporting the topic sentence, and concluding

sentence.
Eliminate unnecessary qualifiers. Look for areas where
phrases such as may want to consider or could be
indicated are used in an effort to hedge your bets.
Wherever possible, rewrite to definitive phrases such as
should consider and is indicated.
Eliminate tangents. Cut out entire paragraphs that are
full of well-researched, interesting information, but are
not 100 % relevant to the main teaching points of the
case.
Have a nonmedical friend or relative read the article
ask them to point out places that are difficult to
understand.
5. Revise for active voice. Optimize the voice of the manu-
script to markedly increase the quality. Take the time to
carefully remove examples of passive voice whenever pos-
sible; reviewers and editors will be able to tell the differ-
ence. Examples:
Passive Active
A basic metabolic panel was The admitting team ordered a
ordered by the admitting team. basic metabolic panel.
A lumbar puncture was The emergency department
performed by the emergency provider performed a lumbar
department provider. puncture.
Magnetic resonance imaging The neurology consultants
was considered by the considered magnetic resonance
neurology consultants. imaging.
By then, the patient would By then, the neurologists would
have been re-evaluated by the have re-evaluated the patient.
neurologists.
6. Double-check the tenses. Write the case presentation

entirely in the past tense. The discussion can include past
and present tense as appropriate. Examples:
Presubmission checklist 161
Past Present Future

Correct Case Case Discussion:
presentation: presentation: The patient will
The patient Figure 1 require yearly CT
presented shows the scans for the rest
with 5 days patients left of his life.
of upper foot.
extremity Discussion:
weakness. Our case
demonstrates
the importance
of taking a
complete
review of
systems.
Incorrect Discussion: Case Case
Our case presentation: presentation:
demonstrated The patient Figure 1 will
the then shows show the patients
importance the rash to the left foot.
of taking a physician.
full review of Case
systems. presentation:
A CT scan is
performed.
7. Eliminate use of the first or second person. Third person is

the preferred style in academic writing. In some instances,
journals allow the use of first or second person (such as if a
discussant is responding to a case presentation in a clinical
reasoning manuscript), but this is rare. Examples:
First person Second person Third person

I, me, my, mine, You, your, He, she, it, him, her, his, her,
we, us, our, ours yours hers, its, they, them, their, theirs
8. Double-check the images. Images can greatly enhance

case reports, but poorly presented images can be distracting.
Take a final look at any included images and verify the

following:
The image should be appropriately cropped. For exam-
ple, if the area of interest is the hand, is it necessary to
include the patients arm and torso?
Clearly identify the finding of interest. Your readers
may not be skilled at interpreting pathology slides or
radiology images. Any arrows should be clearly visible
and unmistakably indicate the area of interest.
The image resolution should be appropriate. If the
image is grainy, it may be best to leave it out.
Responding to Peer Review

Most authors enjoy the respite gained by having a manu-
script out of their grasp and finally under review by a jour-
nal. During this time, it feels like anything is possible.
Perhaps, there will be an e-mail waiting in your inbox from
the editor stating Your submission was magnificent! The
reviewers were astounded by both the fascinating case and
the quality of your writing. We would like to immediately
publish it without further revision. More likely, the mes-
sage will either be, Thank you for your submission.
Unfortunately, your manuscript is not a good fit for our
journal at this time, or We would be interested in consid-
ering a revised manuscript. The reviewers have made a
number of critiques and suggestions. If you would like to
revise and resubmit your manuscript, please respond to
each of the reviewers comments and note all modifications
made to your manuscript. It may not feel like it in the
moment, but this second message is actually great news. This
means that there is a path to publication, provided a revi-
sion is assiduously pursued. The remainder of this chapter
describes the steps to effectively respond to a journals
request for revisions.
Responding to Peer Review 163
Step 1. Break Down the Critique into Manageable

Segments
This ensures that every reviewer comment is addressed, which
is a critical requirement with the submission of a revised manu-
script. Start by creating a chart like the one shown here:
Reviewer #, Reviewer/editor Authors Changes made in
Comment # comments response the manuscript
Sequentially copy segments directly from the review, inde-

pendently listing distinct issues. Do not edit the reviewers
phrasing or omit any of the text in the review this demon-
strates that all of the feedback was taken into consideration.
Depending on the clarity of the review, in many cases, it is
best to keep an entire paragraph intact if it clearly describes
a discrete problem with the manuscript. In other cases, mul-
tiple concepts may be introduced simultaneously, even in the
same sentence. In this case, it is important to dissect the con-
tent to individually define the issues and allow for an orga-
nized response.
For example, a comment from a hypothetical reviewer 1:
Overall, this is an interesting case. However, the case pre-
sentation is disorganized, includes too much irrelevant infor-
mation (the CBC is not necessary), and presents information
nonlinearly. This feedback is best organized as follows:
Changes
Reviewer #, Reviewer/editor Authors made in the
Comment # comments response manuscript
R1C1 Overall, this is an
interesting case.
R1C2 However, the case
presentation is
disorganized
Changes
Reviewer #, Reviewer/editor Authors made in the
Comment # comments response manuscript
R1C3 includes too much
irrelevant information
(the CBC is not
necessary)
R1C4 and presents
information nonlinearly.
Step 2. Examine the reviewer and editor comments

in totality.
After the table is populated with all the reviewer and editor
comments, look for common issues or themes. If multiple
reviewers mention the same issue, it is important to compre-
hensively address this in your response. A repeatedly men-
tioned issue almost certainly represents an area of significant
weakness in the work. Simultaneously, look for areas of con-
tradiction or disagreement between reviewers. For these
issues, the authors must come to consensus on how to respond
appropriately.
Step 3. Draft responses and revisions to the

manuscripts.
Follow these principles to draft your response:

A. Never be offended if the critique was particularly harsh,
take a few days to re-establish comportment before begin-
ning the response.
B. Recognize the difference between a request and a sug-
gestion. Revisions requests should almost always be
completed if the manuscript is to be resubmitted to the
same journal. Most suggestions should also be imple-
mented, but there is more leeway to make and explain a
different tack. See below for some examples:
Requests almost always Suggestions if it is important

implement requested changes to the authorship team, it
is OK to make a reasoned
argument against making
suggested changes
Example requests Example suggestions
The editor specifically Editor asks that authors
requests that a certain consider a reviewers
change is made. comment but does not state
Please remove all use of the full agreement with the
first person. reviewers position.
Please write out all Please note reviewer 2s
abbreviations. concern regarding the
The final diagnosis remains accuracy of the diagnosis.
unclear; please revise so Consider providing the lab
that there is no uncertainty values that were queried.
regarding the diagnosis.
Editor highlights a Reviewer or editor asks
reviewers comments and authors to consider a
requests that attention is revision.
paid to the issue. Consider dividing the
Please attend to reviewer first paragraph into two
2s concern regarding the separate paragraphs
suitability of this case for the the first with the ED
journals audience. presentation and the
second with the initial
work-up.
Reviewer or editor highlights Reviewer or editor
a comment as a major highlights a comment as
comment and emphasizes a minor comment and
the importance of a revision states
to strengthen the manuscript. I suggest mentioning the
I strongly suggest revising hospital day during the
the manuscript to reflect the patients hospital course;
actual clinical course of the this is a style preference
patient. This is a major issue and is at the discretion of
and will require considerable the authors.
revision.
C. Resist the temptation to score points on the editor or

reviewer. It is not difficult to identify inconsistencies and
errors in reviews and comments from editors. Pointing

these out or making subtle slights will not be beneficial to
you. For example, instead of saying, Two reviewers hated
the title (and much of the rest of the manuscript) and one
reviewer loved it we decided to keep it as is, consider
something like, We appreciate that the title elicited
strong reactions from the reviewers. After much consider-
ation of other possibilities, we ultimately agreed with
reviewer 1 and elected to keep the title unchanged; we felt
that the current title best reflected the crux of this case.
D. Use professional and courteous language in phrasing all
responses. Be sure to thank the commenter for any posi-
tive comments. Acknowledge all concerns, repeating the
concern in your response. If reviewer comments have
already been previously addressed in an earlier response,
simply refer to the comment. See below for examples:
Reviewer/
Reviewer #, editor Authors Changes made in
comment # comments response the manuscript
R1C1 Overall, We thank the
this is an reviewer for
interesting the positive
case. comment.
R1C2 However, We appreciate Case presentation
the case the reviewers paragraph
presentation concern 1: Removed
is regarding reference to the
disorganized the overall CT scan and
organization labs that were
of the case obtained later
presentation. in the hospital
We have stay. Added
rewritten physical exam and
the case admission labs.
presentation Case presentation
to accurately paragraph 2:
depict the Added CT scan
sequence of and later lab
events in the results. Removed
order that they physical exam and
occurred. admission labs.
Reviewer/
Reviewer #, editor Authors Changes made in
comment # comments response the manuscript
R1C3 includes We appreciate No changes.
too much that some of
irrelevant the included
information labs may be
(the CBC perceived as
is not being irrelevant
necessary) to the case. We
suggest that
the admission
CBC is quite
germane to the
case, given the
occult bleeding
which occurred
later in the
hospital course.
Therefore, we
have kept the
admission CBC
in the case
presentation,
but moved
it to the first
paragraph (see
R 1 C 2).
R1C4 and Please see Please see
presents response to R response to R 1
information 1 C 2. C 2.
nonlinearly.
Depending on the journal requirements, the changes made

in the manuscript column may or may not need to be
included in the response. In all cases, some sort of tracking is
required to demonstrate changes from the original submission.
This can range from using the track changes function in
Microsoft Word or bolding all changes in the revision.
Step 4. Compose a response letter.
The key components of the response letter are shown below.

Address the letter to the corresponding editor and thank them
for considering the manuscript. Explain how the comments are
being addressed either using a table or by sequential listing.
Journal of Extraordinary Cases

Sophie Snozzcumber, MD, MPH
Deputy Editor
Re: MS # 1217, Major Revision
Dear Dr. Snozzcumber,
We thank you for your review of our manuscript entitled
Macrotia in Micronesia. This manuscript has been substantially revised
for your re-consideration. In this letter we respond to the concerns raised
by yourself and the reviewers. The first column lists the reviewers
comments in their entirety, divided by issue addressed. We have
attached a revision with changes tracked as well as a clean version.
Comments Response
Reviewer 1, Comment 1
Reviewer 1, Comment 2
We would like to thank the Editor and reviewers for their

thoughtful evaluation of our work and insightful comments. We believe
that the consequent changes inthe manuscript have made this a stronger
work, and we look forward to your review of this revised manuscript.
Best regards,
Dr. Mary Clonkers, MD
Conclusion
Every interesting case report has a home somewhere in the
literature. Previous chapters have provided guidance on picking
the right case to report, how to write case reports, and where to
submit them. Follow the tips in this chapter to complete the
process of case reporting and bring your case report home.
References 169
References
1. Pupovac V, Fanelli D. Scientists admitting to plagiarism: a meta-
analysis of surveys. Sci Eng Ethics. 2015;21(5):133152.
2. Garg A, Das S, Jain H. Why we say no! A look through the edi-
tors eye. J Clin Diagn Res. 2015;9(10):JB015.
3. Pierson DJ. The top 10 reasons why manuscripts are not accepted
for publication. Respir Care. 2004;49(10):124652.
Chapter 13
Its Published!
Clifford D. Packer
Fifteen Minutes of Fame
In 1968, Andy Warhol said: In the future, everyone will be

world-famous for fifteen minutes. Warhol seems to have
anticipated the Internet age, where news blips, video clips,
fads, and ideas can go viral in minutes and then disappear
from view just as quickly. In May of 2009, I had my
15 minutes of fame when an obscure editorial I had written
for a second-tier English medical journal became part of the
worldwide medical scare of the week.
It started in 2008, when I published a case report about
one of my patients with a puzzling case of chronic hypokale-
mia that I eventually discovered was caused by long-term
excessive cola consumption [1].The next year, the International
Journal of Clinical Practice (IJCP) contacted me to referee a
review article by three Greek doctors that summarized all the
known cases of cola-induced hypokalemia, and hypothesized
on the pathophysiology of the condition [2]. They also asked
me to write an editorial on the subject, which was published
a few months later along with the review article [3].
Soon afterward, a London PR firm representing IJCP put
out a press release that summarized the review article, and
also quoted my editorial comments on the subject. And
then, well, things happened very fast. The story spread like
wildfire to newspapers, wire services, and health news

DOI 10.1007/978-3-319-41899-5_13
172 Chapter 13. Its Published!
websites the world over. Too Much Cola Zaps Muscle

Power, warned the BBC News headline [4]. Drinking
Large Amounts of Cola Can Cause Paralysis, Doctors
Warn, cried the Daily Telegraph [5]. Mediziner-Warnung:
Kola klaut dem Korper Kraft, trumpeted Der Spiegel [6].
USA Today, ABC News, Reuters, UPI, and newspapers from
New York to Glasgow, Myanmar to Melbourne picked up
the story and ran with it. Cola Drinks Up Paralysis Risk,
according to the Fars News Agency of Tehran. In fact, the
story was picked up and I was quoted in newspapers of
Iran, Iraq, and even North Korea!
During my VA clinic that afternoon, while I was examining
a patient, my office phone rang. It was the press agent work-
ing for IJCP, calling from London. She sounded excited,
almost frenzied: Dr. Packer! Your article on cola-induced
hypokalemia is white-hot right now! Everybody is picking it
up. I just had a call from ABC News in New York they want
to interview you right now. She gave me the name and
phone number of the reporter, and begged me to call them
immediately. Perversely, though, I finished seeing my patients
and dictating my notes (first things first!), and it was 5 oclock
before I nervously dialed the 212 area code and left a mes-
sage on the reporters voice mail. Alas, the story had already
peaked by then, and was on the wane. The half-life of a medi-
cal scare like this is measured in hours, not days. She never
called me back.
Over the next week or two I received one request for an
online interview, and several e-mails from people who
described their own experiences with cola and low potassium,
some of which were dramatic severe muscle weakness and
pain was the common thread. I also received a few e-mails
from medical academics, some of whom thanked me for cor-
roborating their nutritional theories, a couple of which were
a bit on the wacky side. My editorial also found its way into
the Wikipedia article on hypokalemia (see under other
causes) [7]. Interestingly, the review article and editorial also
brought this earnest but somewhat disingenuous press release
from the Coca-Cola company (obviously, they consulted an
Fifteen Minutes of Fame 173
expert who knew something about the limitations of case

reports):
The safety and quality of all our products is paramount and is
something we would never compromise. This has been the case
since we first began making Coca-Cola more than 120 years ago.
The examples used in a paper by the International Journal of
Clinical Practice are all extreme cases of chronic consumption
(39 liters per day). Moderate consumption of cola drinks is safe
and people can continue to enjoy such drinks as part of a sensible,
balanced diet and active lifestyle. The foundation of good nutri-
tion is balance, variety and moderation.
This paper is a review it is not scientific research (ie, clinical
study) and is an insufficient basis to claim cola consumption
causes hypokalaemia. The reported cases of hypokalaemia were
associated with persistent consumption of unusually large quanti-
ties of cola drinks, which does not represent typical cola soft drink
consumption pattern among consumers. Furthermore, the authors
speculate that moderate quantities of caffeine (180360 mg) may
result in hypokalaemia. The observation is not supported by any
well-designed clinical study.
We market our products in a responsible manner and have
taken a leading role to provide fact-based nutrition and health
information for all our products. We believe providing fact-based
nutrition and health information for all our products, supported
by effective consumer messaging and education programs, will
help empower people to select sensible, balanced diets and
become more physically active [8].
It turns out that heavy cola consumption is not rare. An

analysis of data from the National Health and Nutrition
Examination Survey (NHANES) shows that about 510 % of
US teenagers and adults consume at least 2 l of cola or other
sugary drinks per day [9]. Also, I have yet to see how Coca-
Cola is empowering people to select sensible, balanced diets
and become more physically active. I am happy to report,
however, that real progress has been made in removing their
products from US schools in an effort to reduce childhood
obesity.
In 2010, a New Zealand woman died from cola-induced
hypokalemia after years of heavy consumption, and there
was another brief tabloid storm, which soon blew over.
However, there has been a steady trickle of case reports of
profound hypokalemia and myopathy from excessive cola

consumption, some of which I have been asked to referee.
The case report and review published by Sharma and Guber
in 2013 is particularly interesting and well-written, and makes
a strong case that excessive cola consumption should be con-
sidered in the differential diagnosis of hypokalemia [10]. This
awareness could reduce morbidity and perhaps even save
some lives. I am more than happy to have retreated back into
well-deserved and comfortable anonymity, but it is gratifying
to see that cola-induced hypokalemia is becoming a known
condition, and that this knowledge is permanent and will not
go away.
This story shows how a case report can lead to a peer
review request, an invited editorial, a press release, a world-
wide media frenzy, corporate damage control, and new
awareness among physicians of a potential problem. This may
not be the typical course for a case report, but it does
happen.
Peer Review Opportunities

When your case report is published, you may be contacted by
a journal editor and asked to serve as a referee. If the case
report you review is especially interesting or controversial,
and you write a thoughtful appraisal, you may also be invited
to write an editorial or commentary on the case. At that
point, even if the case report and editorial do not go viral, you
will have demonstrated expert knowledge in the field. This
can lead to more requests for reviews and more editorializ-
ing. Peer review can thus be a way to expand ones range of
expertise and influence.
As a direct result of my own published case reports, I
have been invited to referee case reports and research arti-
cles for a broad range of journals, on topics including nutri-
tion, pharmacology, toxicology, oncology, diabetes research,
rheumatology, and hematology. Polymaths excepted, very
few authors are called upon to referee in so many disciplines.
Peer Review Opportunities 175
I am certainly no polymath; I see myself simply as a general-

ist who likes to write case reports and investigate new and
interesting topics. The impulse to write case reports arises
from a love of variety, which is what motivates many of us
to become generalists in the first place.
For authors of case reports, participation in peer review
stimulates academic growth and sharpens critical insight,
while at the same time helping to uphold the validity and
integrity of the editorial process and improve the quality of
published papers. Other benefits, in addition to invitations to
write commentaries or editorials, may include CME credit
(offered by some journals) and increased consideration for
academic promotion. Several authors have commented on
the peer review process and how to referee a scientific paper
[11, 12, 13]; for case reports, as opposed to research articles,
the referee should consider these five specific questions:
1. Is the case description clear and concise, and does it include
all essential clinical and clinimetric data?
2. Is there a satisfactory literature review?
3. Is the case placed in context does the author compare it
with other similar cases and convey what is rare, interest-
ing, or unique about it?
4. Is there a plausible and convincing hypothesis to explain
the clinical event?
5. Is there some discussion of the clinical implications of the
case?
When I refereed case reports of cola-induced hypokale-

mia, metformin-associated lactic acidosis, and vertebral sar-
coidosis, I was able to suggest changes in one or more of the
above areas that led to significant improvements in the
manuscripts and, in some cases, to publication. I also discov-
ered many things such as little-known references, alterna-
tive mechanisms of disease, and previously unconsidered
hypotheses and speculations in the process of reviewing
each paper. Peer review, it seems, can be a compelling schol-
arly experience, and well worth the (uncompensated) effort.
For medical students, residents, and practicing physicians who

do not participate in formal research, publishing case reports
can allow access to the unique responsibilities and enrich-
ments of peer review.
Editorial Writing Opportunities

There are three main pathways to writing editorials for medi-
cal journals. The first is by direct invitation from the journal
editor, which is generally reserved for top experts in the field.
The second is to contact the editor and ask about submitting
an unsolicited editorial; this approach is seldom successful.
The third pathway, as discussed above, is through peer review.
Some journals ask peer reviewers directly: Would you be
willing to write an editorial on this subject? Other journals
may not solicit editorials openly, but a thoughtful referee who
brings out the interesting implications of a paper may very
well be invited to write more about it. When I reviewed the
cola-induced hypokalemia article by Tsimihodimos et al. [2],
I commented on the possible adverse effects of low potas-
sium in a population of heavy cola consumers with cardiovas-
cular disease. This point was then taken up by the authors in
the final version of their paper, and I raised it again in my
invited editorial [3]. Journal editors like this sort of specula-
tion, provided that it has some basis in fact and passes the
plausibility test.
An editorial on the findings of a case report or case series
should be both provocative and circumspect. While the
potential implications of the case can be explored, the
author should avoid unsupported speculations and conclu-
sions. In my editorial, I summarize the points in favor of the
argument that chronic, heavy cola consumption can cause
hypokalemia:
In their review of cola-induced hypokalaemia, Tsimihodimos
et al. make a compelling argument that potassium depletion
should be added to the long list of soft drink-related health prob-
lems. In the cases they describe, chronic consumption of 310
Editorial Writing Opportunities 177
liters of sugar-sweetened cola per day led to severe hypokalae-

mia, hypokalaemic myopathy, and in some cases, hypokalaemic
paralysis. One patient developed hypokalaemic nephropathy and
subsequent nephrogenic diabetes insipidus. In all cases, the
patients symptoms improved, and the hypokalaemia resolved
with potassium repletion and reduction or cessation of cola
drinking. [3]
Another useful function of an editorial is to discuss patho-

physiology and evaluate the proposed mechanisms of the
disease:
The proposed mechanisms of cola-induced hypokalaemia run
practically the whole gamut of electrolyte physiology. First, the
large glucose load can cause both an osmotic diuresis, with
increased renal potassium wasting, and hyperinsulinaemia, caus-
ing intracellular redistribution of potassium. Second, drinks con-
taining large amounts of high-fructose corn syrup send boluses of
largely indigestible fructose into the GI tract, which causes potas-
sium wasting via an osmotic diarrhea. Third, caffeine has been
shown to cause beta adrenergic stimulation, increase
Na+/K + -ATPase via cellular phosphodiesterase inhibition, and
produce metabolic alkalosis, diuresis, and increased renin levels,
all of which may contribute to hypokalaemiaSoft drinks that
combine large amounts of high-fructose corn syrup with caffeine,
such as regular colas, might deplete potassium stores more effec-
tively because of concurrent osmotic and caffeine-mediated
potassium wasting. With his 4 liter per day Pepsi-Cola habit, my
patient was ingesting 396 g of fructose, enough to cause a chronic
low-grade osmotic diarrhea, and 400 mg of caffeine, the equiva-
lent of about 7 cups of coffee. [3]
Finally, the editorialist should avoid, in the words of

Samuel Johnson, the conclusion, in which nothing is con-
cluded [14]. Make the points that can reasonably be made,
touch on the broader implications, and end with an
aphorism:
In addition to the usual questions about alcohol, tobacco, and
illicit drug use, internists need to start asking their adult patients
about soft drink consumption. Cola drinks need to be added to
the physicians checklist of drugs and substancesthat can cause
hypokalaemia. More work is needed on the epidemiology of cola
consumption, hypokalaemia, and cardiovascular disease. Finally,
the soft drink industry needs to promote safe and moderate use
of its products for all age groups, reduce serving sizes and pay
heed to the rising call for healthier drinks. The tale of the thirsty
kangaroo hunter reminds us of the wisdom of Aristotle: In all
things, moderation. [3]
Article Indexing
Those of us who are old enough to remember searching

through the old Index Medicus (a gigantic tome that was hard
to lift and continually out of date) have a great appreciation
for PubMed and Google Scholar. PubMed is a service of the
US National Library of Medicine that provides free online
access to the MEDLINE database of indexed citations and
abstracts to medical, nursing, dental, veterinary, health care,
and preclinical science journal articles. Google Scholar is an
online, freely accessible search engine that allows users to
search the scholarly literature in all fields. Most PubMed-
indexed articles are peer-reviewed, and PubMed-indexed
journals must pass a rigorous review for scope and coverage,
quality of content, quality of editorial work, production qual-
ity, and intended audience [15]. As compared with PubMed,
Google Scholar searches tend to be broader and less specific;
they contain more gray literature such as conference pro-
ceedings, theses, book chapters, and other non-peer-reviewed
articles. Although Google Scholar searches may return twice
as many relevant articles [16], PubMed searches appear to be
more practical for evidence-based patient-care protocols, for
guiding the care of individual patients and for educational
purposes [17].
Most authors prefer to publish in PubMed-indexed jour-
nals, in the belief that their articles will receive more citations
and the prestige of PubMed indexing will help with academic
promotion. Case reports can be more difficult than other
article types to publish in indexed journals, especially with
editorial concerns about the negative effects of case reports
on the all-important impact factor. However, with careful
journal selection and judicious use of indexed case report
Publication Analytics and Social Media 179
journals, such as the Journal of Medical Case Reports, Case

Reports in Medicine, and BMJ Case Reports, the increased
exposure and prestige of PubMed indexing should be possi-
ble for most case reports. Fifteen of the 18 case reports I have
authored or co-authored since 2005 are published in PubMed-
indexed journals.
Publication Analytics and Social Media

Publication analytics can include citations, views, downloads,
web analytics, and multisource metrics such as Altmetric and
ResearchGate scores. Publication analytics measure atten-
tion, not quality; articles can receive attention for many rea-
sons, not all of which are positive. Self-citation may also swell
citation counts and popularity scores. However, analytics can
tell us a number of useful things: who is citing our articles,
how many are reading and discussing them, and what part of
the world they are from.
Case reports are cited less than other types of medical
studies. Patsopoulos et al. reviewed the citation rates of vari-
ous study designs in 2001 and found that <1% of case reports
had 10 citations within 2 years of publication, as opposed to
43.6% of meta-analyses, 29.5% of randomized controlled tri-
als, and a range of 1025% for other study designs [18].
Bhandari et al. had similar results in a study of citations in the
orthopedic literature over a 3-year period, with meta-analyses,
randomized trials, basic science articles, and case reports
receiving 15.5, 9.3, 7.6, and 1.5 citations, respectively [19].
The low early citation rate for most case reports probably
reflects a fundamental difference in the evidence function of
case reports as opposed to randomized controlled trials and
meta-analyses. While some case reports of unexpected thera-
peutic success (such as dramatic responses to cancer treat-
ment) may receive much attention and many citations early
on [20], most case reports describe rare or solitary events
which may or may not recur in future patients. They serve as
a permanent record of the unusual, and only sometimes
when clusters of similar cases begin to appear as harbingers

of a new disease, syndrome, or significant adverse drug reac-
tion. Thus, it is not surprising that many case reports are
hardly cited at all, or pick up citations gradually over the
years as events unfold. Meta-analyses and randomized con-
trolled trials, on the other hand, tend to make a splash early
as they report significant findings or trends with immediate
implications. This explains their high initial citation rates.
In my own case reports, citations tend to accumulate
gradually over time. Of the 18 case reports published since
2005, 13 have been cited, with a total of 77 citations (range
120, average 5.9 citations per case report). Three of the 18
case reports (17%) now have 10 citations, and one, pub-
lished in 2005, has 20. In general, at least 7080 % of the cita-
tions have come more than 2 years after publication, and
citations have continued to accrue steadily over 59 years
in several cases. I strongly suspect, based on an unscientific
sampling of other case reports in addition to my own, that
this slow and gradual pattern of citation is the norm for case
reports. In comparing case reports with other types of
research articles, then, it might be more reasonable to use
10-year rather than 23 year citation rates. Be patient, case
report authors!
In addition to citation rates, other metrics such as
accesses, views, reads, and downloads are com-
monly available on both journal websites and research scor-
ing sites such as Altmetric and ResearchGate. Several
authors have found a strong positive correlation between
early Internet hits or downloads and subsequent citation
rates [21, 22]. Perneger hypothesizes that scientific value
explains the association between hits and citations, and con-
cludes that the number of early hits is a potentially useful
measure of the scientific value of published medical research
papers [22]. For case reports, considering that they deal with
practical patient management in the real world of medicine,
hits may be more important than citations as a measure of
impact. The high ratio of hits to citations for case reports
seems to support this premise. Consider the numbers for
References 181
three of my own open-access case reports: 6484 accesses/10

citations [1], 8337 accesses/9 citations [23], and 2080 accesses/4
citations [24]. This comes to 500900 accesses for every cita-
tion, which suggests not only that people like reading case
reports, but that many must be reading them (we hope!) for
practical reasons such as education and better clinical care.
Altmetric is a system that tracks, collects, and collates the
attention that scholarly articles receive online, and presents
the data on a single web page. It gathers data from three main
sources: social media (Twitter, Facebook, Google+, Pinterest,
and blogs), traditional media (both mainstream and science-
specific), and online reference managers such as Mendelay
and CiteULike. The data are organized by category, and an
Altmetric score is generated that purports to measure both
the quantity and quality of the online response [25].
ResearchGate is a similar service that tracks reads and down-
loads, and generates an RG Score based on both the publi-
cations in an authors profile, and how other researchers
interact with that authors content [26]. For case report
authors, these systems can give insight into the ongoing
response to ones work, irrespective of citations. For example,
over the past week, I know from my ResearchGate page that
seven of my case reports have been read or downloaded a
total of 19 times; eight of the readers were from Brazil, five
from the United States, four from Russia, and one each from
China and the Philippines [27]. While the practical utility of
this information is unclear in terms of promotion or career
advancement, it is certainly good for morale to know that
people around the world are reading ones case reports.
References
sumption: a case report. Cases J. 2008;1(1):32.
2. Tsimihodimos V, Kakaidi V, Elisaf M. Cola-induced hypokalae-
mia: pathophysiological mechanisms and clinical implications.
Int J Clin Pract. 2009;63(6):9002.
3. Packer CD. Cola-induced hypokalemia: a super-sized problem.

Int J Clin Pract. 2009;63(6):8335.
4. BBC News. Too much cola zaps muscle power. http://news.bbc.
co.uk/2/hi/health/8056028.stm. Accessed 5 Mar 2016.
5. The Telegraph. Drinking large amounts of cola can cause paraly-
sis, doctors warn. http://www.telegraph.co.uk/news/science/
science- news/5350530/Drinking-large-amounts-of-cola-can-
cause-paralysis-doctors-warn.html. Accessed 5 Mar 2016.
6. Spiegel On Line. Mediziner-Warnung: Cola klaut dem Krper
Kraft http://www.spiegel.de/wissenschaft/mensch/mediziner-
warnung-cola-klaut-dem-koerper-kraft-a-625807.html. Accessed
5 Mar 2016.
7. Wikipedia. Hypokalemia. https://en.wikipedia.org/wiki/
Hypokalemia. Accessed 5 Mar 2016.
8. Coca-Cola Company Statements. Statement on cola-induced
hypokalemia. http://www.coca-colacompany.com/press-center/
company-statements/statement-on-cola-induced-hypokaleae-
mia/. Accessed 5 Mar 2016.
9. Packer CD. Letter to the editor: reply. Int J Clin Pract.
2009;63(10):15456.
10. Sharma R, Guber HA. Cola-induced hypokalemia a case
report and review of the literature. Endocr Pract. 2013;19(1):
e213.
11. Pyke DA. Writing and speaking in medicine. How I referee. Br
Med J. 1976;2(6044):11178.
12. Neill US. How to write an effective referee report. J Clin Invest.
2009;119(5):105860.
13. Ajao OG. Peer review and refereeing in medicine and medical
sciences. Saudi J Gastroenterol. 1997;3:10712.
14. Johnson S. The Works of Samuel Johnson, vol. 7. Troy: Pafraets
Press; 1903. p. 156.
15. US National Library of Medicine Fact Sheet. MEDLINE
Journal Selection. https://www.nlm.nih.gov/pubs/factsheets/jsel.
html#. Accessed 20 Mar 2016.
16. Shariff SZ, Bejaimal SA, Sontrop JM, et al. Retrieving clinical
evidence: a comparison of PubMed and Google Scholar for
quick clinical searches. J Med Internet Res. 2013;15(8):e164.
17. Anders ME, Evans DP. Comparison of PubMed and Google
Scholar literature searches. Respir Care. 2010;55(5):57883.
18. Patsopoulos NA, Analatos AA, Ioannidis JP. Relative citation
impact of various study designs in the health sciences. JAMA.
2005;293(19):23626.
References 183
19. Bhandari M, Busse J, Devereaux PJ, et al. Factors associated

with citation rates in the orthopedic literature. Can J Surg.
2007;50(2):11923.
20. Nieder C, Pawinski A, Dalhaug A. Contribution of case reports
to brain metastases research: systematic review and analysis of
pattern of citation. PLoS One. 2012;7(3):e34300.
21. Deciphering citation statistics. Nat Neurosci. 2008;11(6):619.
22. Perneger TV. Relation between online hit counts and subse-
quent citations: prospective study of research papers in the
BMJ. BMJ. 2004;329(7465):5467.
23. Packer CD, Hornick TR, Augustine SA. Fatal hemolytic anemia
associated with metformin: a case report. J Med Case Rep.
2008;2:300.
24. Chiang E, Packer CD. Concurrent reactive arthritis, Graves
disease, and warm autoimmune hemolytic anemia: a case report.
Cases J. 2009;2:6988.
25. Altimetric score. https://help.altmetric.com/support/solutions/
articles/6000059309-about-altmetric-and-the-altmetric-score.
26. RG Score. A new way to measure scientific reputation. https://
www.researchgate.net/publicprofile.RGScoreFAQ.html .
27. ResearchGate Stats. https://www.researchgate.net/profile/
Clifford_Packer/stats. Accessed 25 Mar 2016.
Chapter 14
The Future of the Case
Report
Clifford D. Packer
When evidence-based medicine purists raise the argument

that case reports are a weak form of evidence, I recall an old
joke from one of my college philosophy courses. A logical
positivist bought his fiance a ring. When he presented it to
her, she broke into tears. Its not engraved, dear cant you
have it engraved? Certainly, he replied and rushed back
to the jeweler, had the ring engraved, and raced back to give
it to her. On looking at it, to the astonishment of the logical
positivist, she again began to sob inconsolably. What on
earth is wrong? asked the logical positivist. I had it
engraved exactly as you asked. Of course, as you may have
guessed, it was engraved with the word: Ring.
Now think of the logical positivist as evidence-based medi-
cine; his fiance is the individual patient, and the ring is the
proposed treatment. The ring was engraved correctly based
on strong empiric evidence that it was indeed a ring; the per-
sonal touch, however, was sorely lacking. In a future where
the demand for personalized medicine will almost certainly
increase, the case report or aggregations of case reports
will play an increasingly important role in delivering care that
fits the characteristics of the individual patient.
In this book, we have discussed how the case report can be
used in hypothesis-generation, identification of new syn-
dromes, pharmacovigilance, and as evidence for patient care
decisions when randomized trials are unavailable. We have

DOI 10.1007/978-3-319-41899-5_14
186 Chapter 14. The Future of the Case Report
touched on ways in which case reports can serve in personal-

ized medicine, such as n-of-1 trials and genomic studies of
outlier cancer survivors. These trends will undoubtedly con-
tinue. In addition, we will see increasingly broad and innova-
tive uses of aggregated case reports, patient registries, and
other clinical databases. It has been estimated that our cur-
rent databases collect only about 20 % of the data contained
in medical texts[1]; case reports represent an enormous
potential reservoir of knowledge that is largely untapped at
the present time [2]. As our data-mining and biometric tech-
nologies improve, case reporting will begin to merge with
population medicine and population health. Aggregation of
case reports will help us to collect usable evidence in patients
with multiple chronic conditions, such as diabetes, hyperten-
sion, COPD, heart failure, and cancer, where the interplay of
disease and treatment variables is too complex to be studied
with randomized controlled trials. As Jonathan Teich has said:
The sweet spot is where there are variations and unknowns. While
we know how to treat COPD patients, there may be answers con-
tained in populations about how the disease affects certain demo-
graphics. Using a large population lets you mine for that
information. You can ask a lot of questions of that data and find
something you weren't looking for. [1]
Potential roles for case report databases could include

investigating the interdependence of sequential events;
assessing the efficacy of various treatment schedules, doses,
and regimens; evaluating concomitant or causal comorbidi-
ties; and improving our contingency decision-making in com-
plex patients, using real-life examples [3]. Eventually, as
electronic data collection grows more and more pervasive, I
expect that every patient encounter will become a de facto
case report, in the sense that every encounter will contribute
real-time data to a massive database. At the same time, infor-
mation will flow from the database back to the physician to
support clinical decision-making at the point of contact. More
cases, more data; more data, better care.
Because they capture novelty and innovation, case reports
tend to flourish at the cutting edge of new technologies.
Chapter 14. The Future of the Case Report 187
Consider a recently published case report by Rudner et al. in

Annals of Emergency Medicine, Interrogation of patient
smartphone activity tracker to assist arrhythmia manage-
ment[4]. In this case, it was determined that a patient with
new atrial fibrillation was safe for immediate cardioversion
when examination of his wrist activity tracker revealed that
the arrhythmia had occurred within the past 3 hours. The
patient was safely and successfully cardioverted in the emer-
gency room. This was the first reported use of the information
in a smartphone activity-tracking system to assist in specific
medical decision-making. The case report received extensive
media coverage, including a story on National Public Radio
[5]. Another exciting new technology is the liquid biopsy,
where blood testing for circulating tumor DNA (ctDNA)
shows great promise as a tool for diagnosing cancer, identify-
ing mutations to guide treatment, detecting relapses, and
exploring mechanisms of tumor resistance, while allowing
cancer patients to avoid painful and invasive biopsies [6]. Case
reports and case series will play an important role in develop-
ing clinical applications for ctDNA testing. For example, a
recent case report describes the use of ctDNA multiplex geno-
typing in a patient with metastatic non-small cell lung cancer
and rapidly progressive liver metastases. The test identified a
novel ALK translocation as the mechanism of tumor resis-
tance, without the need for a risky liver biopsy [7]. The patient
then had excellent clinical responses to two different ALK
inhibitors. We should expect to see many more such case
reports highlighting new technologies in the coming decades.
What will case reports look like in the year 2050? Will
Cherenkov radiation and nanoparticle imaging be the stan-
dard of care? Will 3D holograms replace the routine chest
X-ray? And will genomic profiling be as easy and accessible
as ordering a CBC? Whatever technologies evolve, case
reports will be there at the forefront, and I hope and
expect that the basic form and function of the case report
will not change. However compelling the image, however
powerful the technology, we must put the case in context,
explain it, and find out what it has to teach us.
188 Chapter 14. The Future of the Case Report
References
1. Healthcare IT News: populations hold key to future medicine.
http://www.healthcareitnews.com/news/populations-hold-key-
future-medicine. Accessed 29 Apr 2016.
2. Jackson D, Daly J, Saltman DC. Aggregating case reports: a way
for the future of evidence-based health care? Clin Case Rep.
2014;2(2):234.
3. Kidd MR, Saltman DC. Case reports at the vanguard of 21st
Century medicine. J Med Case Rep. 2012;6:156.
4. Rudner J, McDougall C, Sailam V, Smith M, Sacchetti A.
Interrogation of patient smartphone activity to assist arrhythmia
management.Ann Emerg Med.2016.pii:S0196-0644(16)00143-148.
[Epub ahead of print].
5. A Fitbit Saved His Life? Well, Maybe. http://www.npr.org/
sections/health-shots/2016/04/11/473393761/a-fitbit-saved-his-
life-well-maybe. Accessed 30 Apr 2016.
6. Chi KR. The tumour trail left in blood. Nature. 2016;532:26971.
7. Liang W, He Q, Chen Y, Chuai S, Yin W, Wang W, et al. Metastatic
EML4-ALK fusion detected by circulating DNA genotyping in
an EGFR-mutated NSCLC patient and successful management
by adding ALK inhibitors: a case report. BMC Cancer. 2016;16:62.
Index
A Airway obstruction, 2324

ACP. See American College of Altmetric score site, 179181
Physicians (ACP) American College of Physicians
Acquired immune deficiency (ACP), 28, 122, 124
syndrome (AIDS), 5, 16, Annals of Thoracic Surgery, 152
35, 45, 91, 106 Antimicrobial therapy, 25, 26
Acquired immunity, 11 Aphorisms, 10
Adverse drug reaction (ADR) Atenolol, 2, 3
case report Authorship responsibilities,
azathioprine 5961
hypersensitivity, 101 Automated submission system,
dose related/augmented type, 97 158
drug interaction case reports, 99 Autopsy, 13, 14
iatrogenic Cushings
syndrome, 101
mechanism of reaction, 101 B
Naranjo scale, 98, 100 Bartters syndrome, 108
patients platelet counts, 99 Behcets syndrome, 29
pharmacovigilance, 97 British Medical Journal (BMJ),
postmarketing 54, 56, 57, 179
surveillance, 98
quality and clinical usefulness,
102 C
ritonavir and oral budesonide, Canadian Medical Association
101102 Journal (CMAJ), 110
timeline, 98 Cannabinoid hyperemesis
Adverse events, 45 syndrome, 28, 66
Aequanimitas, 15 Career enhancement, 3940
AIDS. See Acquired immune Case presentation, 67, 68, 72, 163
deficiency syndrome CAse REport (CARE)
(AIDS) guidelines, 1819, 36, 93

DOI 10.1007/978-3-319-41899-5
190 Index
Case reports discussion, 77, 79, 80

abstract, 6769 effective and succinct
aggregations of, 185 introductions, 7071
in ancient and medieval times electronic case report
Chinese case reports, 12 journals, 18
diabetes mellitus, ancient evidence-based medicine, 185
Hindu text on, 9 evidence value of, 45
Egyptian medicine, 910 form and function, in twenty
European case reports, 12 first century, 67
Galens On the Affected future case reports, 18
Parts, 11 hypothesis development
Hippocratic case histories, 10 aggressive gastric
Rhazes, case histories of, carcinoma, 89
1112 hemangiomas, 85
authorship responsibilities, lithium toxicity, 87
5961 plausibility (and
brevity, 70 publishability), 88
CARE checklist, 93 propranolol, 85
career enhancement, 3940 steps in, 86
CARE guidelines, 1819, 93 supposition/proposed
case description explanation, 84
clinimetrics, 71 TCMA, 87, 88
diagnostic assessment, 75 TIA mimics, 87
Duke criteria score, 72 Warburg effect, 89
essential elements, 72 watershed zones, 88
laboratory test results, 74 images and data collection,
physical examination, 74 5859
prescribed medications, 73 impact of, 56
serum potassium values, 73 informed consent to
clinical decision-making, 186 publication
clinical presentation, 69 BMJ Case
cola-induced hypokalemia, 3 Reports, 54, 56, 57
context of ICMJE, protection of
acute obstructive privacy, 5556
suppurative pancreatic just write something, 6162
ductitis, 8283 liquid biopsy, 187
advanced search tool, 80 medical literature, 3436
clinical presentation and medical students and
bacteriology, 84 residents, 3839
clinical setting, 80 modern case report, origins of
direct Coombs test, 80 Charcots case report, 14
literature review, 80 heart disease, distressing
metformin-induced effects of, 14
hemolytic anemia, 81 Oslers interspecies case
ctDNA testing, 187 report, 1416
data-mining and biometric Parkinsons Essay on the
technologies, 186 Shaking Palsy, 1314
Index 191
Pomatas Observationes, Clinical images

1213 article, 109111
syphilitic abdominal aortic Clinical problem solving (CPS)
aneurysm, 15 manuscript
Warrens Remarks on case discussion construction,
Angina Pectoris, 13 139144
patient care, 3738 aliquots, 139140
personalized medicine, antiphospholipid
185, 186 syndrome, 143
population medicine and arthralgias, 141
health, 186 commentary
as reports from the section, 144
frontline, 5 embolic phenomena, 142
speculation, 9091 extemporaneous
teaching point, 9192 thinking, 139
timeline, 7577, 79 invasiveness and
title, 6566 adherence, 143
in twentieth century, 1617 magnetic resonance
vibrato, atenolol effects imaging, 142, 144
on, 23 nephrotic syndrome, 143
Case Reports in Medicine, 179 next-to-last aliquot, 140
Case series patients progressive
case-control studies, 105 dyspnea, 140
childhood Bartters reported problems
syndrome, 108 duration, 140
comparison table, 107 specialty-level inquiries, 144
cross-sectional studies, 106 symptoms and history, 142
disadvantages, 106 teaching points, 144
immune suppression transesophageal
hypothesis, 106 echocardiography, 142
limitations of, 109 case protocol construction,
MMR vaccination, 106 138139
Patients and Methods case selection, 135136
section, 107 clinical reasoning
pneumonia and Kaposis clinical information, 145
sarcoma, 106 clinician, 146
statistical analysis, 105 diagnostic reasoning, 146
teaching points, 108 JGIM ECR, 145
Cellulitis, 10 problem representation, 147
Centers for Disease Control clinical teaching points
(CDC), 35, 45, 153 authorship, 150
Chen Hue, 12 final author, 150
Chinese case reports, 12 final steps, 148149
Circulating tumor DNA first author, 149
(ctDNA), 187 middle authors, 149
CiteULike, 181 manuscript writing, 140
Claudication, 1415 planning stage, 136137
192 Index
Clinical quiz/mystery image D

antimicrobial susceptibility Data Protection Act, 57
testing, 115 Diabetes mellitus, 9, 68, 70
vs.clinical images, 116117 Drug Interaction Probability
post-intubation tracheal Scale (DIPS), 99
stenosis, 112, 113 Duke criteria score, 72
subspecialty journals, 115
teaching points, 114
tracheal stenosis case, 115 E
When Asthma is Not Early warning system, 90
Asthma, 112 Ebers papyrus, 9
Clinical vignette abstracts Ebola virus, 5, 25, 26
academic style of writing, Ebsteins anomaly, 29
124125 Editorial writing, 176178
case description, 123 Educational benefits
chief complaint, 125 of reading case reports
clinical encounter, 125126 Ebola virus infection, 25, 26
focused discussion infectious mononucleosis,
case report authors, 131 2325
key points, 132 prostate cancer,
teaching points, metastatic, 2627
131132 recognition patterns, 26
lab values, 127128 of writing case reports
learning objectives for medical students and
as actions, 129130 residents, 2729
important lessons, 129 for practicing physicians, 30
lengthy and run-on sentences, Egyptian medicine, 910
avoiding, 126127 Egyptian papyrus, 910
objective data, 127 Electronic case report journals, 18
opening sentence, 123124 Epidemics, 7, 10
peer review of, 122 Essay on the Shaking Palsy,
physical examination 1314, 45
findings, 126 European case reports, 12
relevant examination findings, Evidence-based medicine, 17,
inclusion of, 127 3437, 185
reporting data, 129 Exceptional Responders
section headings, 126 Initiative, 104
site of care, 125
tests, 128
unnecessary information, F
avoiding, 128129 Fetal microcephaly, 5
word limits/style, 123 Foot infection, 10
Cola-induced hypokalemia, 3, 86,
90, 171177
Collaborative writing, 27 G
CONSORT guidelines, 35 Galen, 11
Coombs test, 68, 71 Genomic sequencing, 67
Index 193
Glasgow Coma Scale, 72 Clinical Reasoning

Google Scholar, 178 series
(JGIM ECR), 145
Journal of Hospital Medicine
H (JHM), 137
Heart disease, 14, 90, 98 Journal of Medical Case
Hippocrates, 10, 11, 91 Reports, 179
History of present illness Journal of Paediatrics and Child
(HPI), 139 Health, 54
Hypertension, 2, 3, 66, 73, 92, 101
Hypokalemia, 3, 65, 70, 7375, 86,
90, 92, 101, 108, K
171176 Kissing tonsils, 23, 24
Klebsiella pneumoniae, 115
I
ICMJE. See International L
Committee of Medical Lectures on Literature, 3
Journal Editors Left upper quadrant (LUQ)
(ICMJE) abdominal
IJCP. See International Journal pain, 145, 146
of Clinical Practice Leg claudication, 15
(IJCP) Liquid biopsy technology, 187
Index Medicus, 178 Lusitanus, Amatus, 12
Infectious mononucleosis, 2325
Informed consent
BMJ Case Reports, 54, 56, 57 M
ICMJE, protection of privacy, Manuscript review
5556 presubmission checklist
Intermittent claudication, 14, 15 active voice, revise for, 160
International Committee of clarity and flow, re-reading
Medical Journal for, 159160
Editors (ICMJE), double-checking images,
5556, 60 161162
International Journal of Clinical double-checking tenses,
Practice 160161
(IJCP), 171, 173 first/second person usage,
Interspecies case report, 1416 elimination of, 161
Islamic medicine, 1112 plagiarism, 158159
re-reading manuscript, 158
submission guidelines,
J 157158
Journal of General Internal revised manuscript
Medicine critical requirement,
(JGIM), 47, 137, 145 163164
Journal of General Internal draft responses and
Medicine Exercises in revisions, 164168
194 Index
Manuscript review (cont.) phenotypic monitoring

reviewer and editor devices, 104
comments, 164 prazosin, 104
Manuscript submission process RCTs, 103
abstract, 155
journal and format selection,
153154 O
journals guidelines, 154 Observationes, 12
predatory publishers, 154 Onchocerca lupi infection, 35
section requirements, 155 Online case report journals, 18
target audience, 151152 Online reference managers, 181
word count and formatting, 155 On the Affected Parts, 11
Measles, 11, 106 Open-access electronic case
Measles, mumps and rubella report journals, 18
(MMR) vaccination, 106 Osler, William, 1416, 30
Medical literature
CARE guidelines, 36
CONSORT guidelines, 35 P
evidence-based medicine, Parasite-derived cancer cells, 16
3436 Parkinson, James, 1314, 45
PRISMA, 35 Past medical history (PMH), 139
Medical students, case reports Patient care, 3738, 45, 67, 185
for, 2729, 3839 Peer review process, 1, 2, 18, 27,
Mendelay, 181 122, 154, 162168,
MeSH database, 80 174176
Metformin-associated lactic Pharyngeal airway obstruction,
acidosis, 175 23, 25
Morbidity and Mortality Weekly Phenotypic monitoring devices,
Report (MMWR), 35, 45 7, 104
Pneumocystis pneumonia, 35, 45
Pomata, Gianna, 1213
N Presubmission checklist
Naranjo Adverse Drug Reaction active voice, revise for, 160
Probability Scale, 72 clarity and flow, re-reading
National Health and Nutrition for, 159160
Examination Survey double-checking
(NHANES), 173 images, 161162
National Institutes of tenses, 160161
Health, 153 first/second person usage,
New England Journal of elimination of, 161
Medicine (NEJM), plagiarism, 158159
109110, 137, 140 re-reading manuscript, 158
N-of-1 trials submission guidelines,
anecdotal cases, 103 157158
clinical decision-making, 105 PRISMA, 35
imprecision medicine, 103 Prostate cancer, 26, 28
individual patients, 102 Publication analytics, 179181
Index 195
Publication criteria, case reports Septicemia, 25, 26

adverse events, 45 SHM. See Society of Hospital
categories of, 46 Medicine (SHM)
characteristics, 4445 Smallpox, 11
medical science, Social media, 179181
contribution to, 46 Society of General Internal
modified five-question Medicine (SGIM), 28,
algorithm, 4749 122, 124
reflection/perspective Society of Hospital Medicine
pieces, 4546 (SHM), 122, 124
treatment, 47 Stone Mountain Medical Case
Published case reports Histories of Wang Ji, 12
article indexing, 178179 Students, case reports for, 2729,
chronic hypokalemia, 171 3839
editorial comments, 171 Subspecialty journals, 115, 152,
editorial writing 158
opportunities, 176178 Syphilitic abdominal aortic
heavy cola consumption, 173 aneurysm, 15
IJCP, 171
limitations of, 173
peer review opportunities, T
174176 Take-home points, 148, 152
publication analytics and TCMA. See Transcortical motor
social media, 179181 aphasia (TCMA)
review article, 171 TEACH, 135136
PubMed, 80, 105, 154, 178, 179 TNM cancer staging, 72
Tonsillar hypertrophy, 23
Traditional media, 181
R Transcortical motor aphasia
Randomized controlled trials (TCMA), 87, 88
(RCTs), 45, 17, 103 Two cheers for case reports, 43
Recognition patterns, 26
Remarks on Angina Pectoris, 13
ResearchGate score site, 179181 V
Response letter, 168 Verminous aneurysms, 14
Revised manuscript Vertebral sarcoidosis, 6668,
critical requirement, 163164 92, 175
draft responses and revisions, Veterinary medicine, 14, 15
164168 Vibrato, 23, 66
reviewer and editor
comments, 164
Rhazes, 1112 W
Warren, John, 13
S
Self-citation, 179 Z
Sepsis, 10 Zika virus infection, 5

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Clifford D.

Writing Case Reports

Writing Case Reports

ISBN 978-3-319-41898-8 ISBN 978-3-319-41899-5 (eBook)

Library of Congress Control Number: 2016955956

Springer International Publishing Switzerland 2017

Printed on acid-free paper

This Springer imprint is published by Springer Nature

CDP acknowledges his medical students,

GB dedicates this book to all the students and

GB wishes to thank her colleagues at the University

SM dedicates this book to his best friend,

SM wishes to acknowledge the University of

Cleveland, OH, USA Clifford D. Packer, MD

2 The Historical Tradition of Case Reporting . . . . . . . 9

3 The Educational Value of Case Reports . . . . . . . . . . 23

4 Practical Benefits of Case Reporting . . . . . . . . . . . . . 33

5 Is My Case Good Enough? . . . . . . . . . . . . . . . . . . . . 43

6 How to Get Started . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

7 How to Write a Traditional Case Report. . . . . . . . . . 65

9 How to Write a Clinical Vignette Abstract . . . . . . . . 121

10 How to Write a Clinical Problem

11 Submitting a Case Report Manuscript . . . . . . . . . . . . 151

12 The View from the Journal . . . . . . . . . . . . . . . . . . . . . 157

13 Its Published! . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

14 The Future of the Case Report . . . . . . . . . . . . . . . . . . 185

Gabrielle N. Berger, MD Division of General Internal

Gurpreet Dhaliwal, MD Department of Medicine, University

Brian J. Harte, MD Department of Medicine, Cleveland

Somnath Mookherjee, MD Division of General Internal

Clifford D. Packer, MD Case Western Reserve University

Jeffrey Wiese, MD Department of Internal Medicine, Tulane

Writing Case Reports

There are many good reasons to write case reports: to edu-

Springer International Publishing Switzerland 2017 1

clinical problem-solving cases. These chapters have numerous

The Violinist Who Lost His Vibrato

is produced by quick oscillations of the violinists hand to

Evidence Value of Case Reports: What

Case reports may remain the lowest or weakest level of

search will usually yield a handful of similar cases that may

Impact of Case Reports

mechanisms of disease (Chap. 7), medical education (Chaps. 3, 8,

Case Reports: Form and Function

Traditional case report

N-of-1 trial Pharmacogenomic

Clinical problem-solving case

Clinical reasoning case

Figure 1.1 Taxonomy of the twenty first century case report

specific treatment. Similarly, n-of-1 trials of patients with

7. Mlakar J, Korva M, Tul N, Popovi M, Poljak-Prijatelj M, Mraz

The Case Report in Ancient

The medical case report as we know it today is not a static

Springer International Publishing Switzerland 2017 9

entwined with magic [3]. In contrast, the Hippocratic case

Hippocrates crowning achievement was the Aphorisms, a

In the modern case report, it is still customary to conclude

Galen (129ca.200 AD), the eminent Greek physician and

Galen made many brilliant observations, and his medical

Origins of the Modern Case Report

As the Enlightenment eased religious restrictions, autopsy

In his Essay on the Shaking Palsy (1817), James Parkinson

Note the personification (exhausted nature) and the