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Clinical Nutrition (2008) 27, 515

Available at www.sciencedirect.com

http://intl.elsevierhealth.com/journals/clnu

REVIEW

Prognostic impact of disease-related malnutrition

Kristina Normana, Claude Pichardb, Herbert Lochsa, Matthias Pirlicha,
a

Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, ChariteUniversitatsmedizin Berlin, Berlin b Department of Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland Received 27 September 2006; accepted 12 October 2007

KEYWORDS
Malnutrition; Prognostic impact; Morbidity; Mortality; Length of hospital stay; Costs

Summary This review focuses on the studies investigating the prognostic implications of diseaserelated malnutrition. Malnutrition is a common problem in patients with chronic or severe diseases. Prevalence of hospital malnutrition ranges between 20% and 50% depending on the criteria used in order to determine malnutrition and the patients characteristics. Furthermore, nutritional status is known to worsen during hospital stay which is partly due to the poor recognition by the medical staff and adverse clinical routines. Studies have repeatedly shown that clinical malnutrition however has serious implications for recovery from disease, trauma and surgery and is generally associated with increased morbidity and mortality both in acute and chronic diseases. Length of hospital stay is signicantly longer in malnourished patients and higher treatment costs are reported in malnutrition. Since it has been demonstrated that proper nutritional care can reduce the prevalence of hospital malnutrition and costs, nutritional assessment is mandatory in order to recognise malnutrition early and initiate timely nutritional therapy. & 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Contents Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Denition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Causes for malnutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevalence of malnutrition in hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical implications of malnutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Perioperative morbidity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Corresponding author. Tel.: +49 30 450 514062; fax: +49 30 450 514901.

6 6 7 8 8 8 8

E-mail address: matthias.pirlich@charite.de (M. Pirlich). 0261-5614/$ - see front matter & 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. doi:10.1016/j.clnu.2007.10.007

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6 K. Norman et al. Morbidity in chronic disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Morbidity in acute disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Functional impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Length of hospital stay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Economical implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Conict of interest statement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Background
Malnutrition remains a signicant problem in hospital despite the growing body of evidence describing both its clinical and economical consequences. Depending on the denition used, the prevalence of hospital malnutrition is reported to range between 20% and 50% (see Table 1). In elderly patients1 and in some settings such as in oncology2 this rate is even higher. Although malnutrition undeniably promotes morbidity and appropriate nutritional therapy is available in the afuent

countries, there is evidence that only a small percentage of malnourished patients is receiving nutritional support.24 This has mainly been attributed to the poor awareness and the lack of education of the attending hospital staff and adverse hospital routines.3

Denition
Malnutrition has been described as the imbalance between intake and requirement which results in altered

Table 1 Author

Prevalence of hospital malnutrition in studies reported after 1990 according to country and discipline. Country
127

Discipline Abdominal- or thoracic surgery General medicine Geriatrics Surgery General surgery Internal medicine Respiratory medicine Orthopaedics Geriatrics General surgery General surgery Intensive care Internal medicine Geriatrics Internal medicine Surgery General surgery General medicine Respiratory medicine Geriatrics Orthopedics Multidisciplinary Multidisciplinary Multidisciplinary Multidisciplinary General medicine and surgery Multidisciplinary Multidisciplinary

n 2448 228 47 331 100 100 100 100 100 199 205 129 155 201 4000 244 232 198 60 26 53 750 995 9348 1000 850 590 1886

Prevalence (%) 39 38 45 37 46 27 45 39 43 35 20 43 45 31 48.1 39 7 13 18 15 9 22 31.3 50 47 20 39.9 27.4 41.7 31.4

VA Study Group Coats et al.128 Lansey et al.129 Mowe et al.130 McWhirter and Pennigton3

USA USA USA Norway Scotland

Larsson et al.131 Cederholm et al.132 Giner et al.109 Naber et al.86 Gariballa et al.91 Waitzberg et al.133 Bruun et al.134 Corish et al.135

Sweden Sweden USA Netherlands UK Brazil Norway Ireland

Kondrup et al.49 Kyle et al.136 Correia and Campos2 Wyszynski et al.137 Malnutrition Prevalence Group138 Rasmussen et al.4 Pirlich et al.1

Denmark Switzerland Latin America Argentina UK Denmark Germany

Weighted mean of all listed studies Weighted mean of the US and European studies

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Prognostic impact of disease-related malnutrition metabolism, impaired function and loss of body mass5 or as a state of nutrition in which a deciency or imbalance of energy, protein, and other nutrients causes measurable adverse effects on tissue and/or body form.6 However, there is still no internationally accepted criterion for diagnosing malnutrition which probably explains part of the reported wide range of malnutrition prevalence in hospital. Weight loss (410% in 6 months) which has been proven to be a good predictive parameter on its own7 is part of most published nutritional scores such as the Subjective Global Assessment (SGA),8 the Nutritional Risk Index (NRI),9 the Mini Nutritional Assessment (MNA),10 the Malnutrition Universal Screening Tool (MUST)11 developed by British Association for Parenteral and Enteral Nutrition, and the Nutritional Risk Score (NRS-2002),12 recommended by the European Society for Clinical Nutrition (ESPEN).13 A recently published study has shown that NRS-2002, MUST and NRI are all able to discriminate malnourished from well nourished patients when compared with SGA as criterion method. Furthermore, nutritional status as assessed by these four scores was associated with increased length of hospital stay.14 7 insulin growth factor-1 have been extensively studied in recent years, their relevance is however not yet entirely understood.16 In some cancers, the proteolysis inducing factor (PIF)17 and lipid mobilising factor (LMF)18,19 have been identied to play a major role in the pathogenesis of the cachexia syndrome. Drug-related side effects: (e.g. chemotherapy, morphine derivatives, antibiotics, sedatives, neuroleptics, digoxin, anti-histamines, captopril, etc.) can cause anorexia or interfere with the ingestion of food. In geriatric patients further factors such as dementia, immobilisation, anorexia, and poor dentition can further worsen the situation.20,21 The reasons for developing malnutrition in sickness are multifactorial, but decreased nutritional intake, increased energy and protein requirements, increased losses together with inammation probably play the central role (see Figure 1). The aetiology and prevalence of malnutrition in different diseases and settings are extensively discussed in the recently published ESPEN guidelines on enteral nutrition.2231 Apart from the pathological causes for malnutrition, socioeconomic factors such as low income and isolation may also contribute to the development of malnutrition.32 Malnutrition is frequent in the sick elderly,3335 in patients with malignant36 or severe disease such as chronic liver disease,3739 chronic heart disease,40 renal insufciency,41 HIV/AIDS,42 COPD,43,44 inammatory bowel disease,45 and cystic brosis46 as well as neurodegenerative disease.47 The situation can be further aggravated in hospital due to adverse hospital routines that lead to insufcient nutrient intake.48 Several studies have found evidence to suggest that hospitalised patients often receive less than an optimal level of nutritional care due to lack of training and awareness of hospital staff.49 Patients are frequently ordered nil by mouth without being fed by another route or are called to an investigation immediately prior to the food being served, multiple episodes of fasting before

Causes for malnutrition

In developed countries the main cause of malnutrition is disease. Any disorder, whether chronic or acute, has the potential to result in or aggravate malnutrition in more than one way: response to trauma, infection or inammation may alter metabolism, appetite, absorption, or assimilation of nutrients.15 Mechanical obstructions in the gastrointestinal tract may lead to reduced food intake by causing nausea or vomiting, pain or discomfort induced by the passage of food. The catabolic effects of several mediators such as cytokines (interleukin 1, interleukin 6, and tumour necrosis factor alpha), glucocorticoids, catecholamines, and the lack of

CHRONIC ILLNESS Cancer AIDS COPD Anorexia Malabsorption ACUTE ILLNESS Infection Trauma Burns Hemorrhage Pancreatitis

Starvation

MALNUTRITION

Inflammatory response

STRESS-related CATABOLISM

Frequent infection Altered intestinal function Altered healing Impaired muscle function

Figure 1 Vicious circle of the development and progression of disease-related malnutrition. Most chronic or severe diseases cause anorexia which results in malnutrition. Malnutrition together with stress-related catabolism caused by inammation increases the risk for infections, organ dysfunction and impaired healing. This againas all other severe acute illnessescan be a trigger for inammatory response and consecutively result in starvation and catabolism which further aggravates malnutrition.

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8 an investigation occur and meals are often considered unpalatable. Depression, dementia, and lack of feeding assistance lead to further decreased nutrient intake.50,51 Since disease is one of the major factors for malnutrition and the risk for malnutrition increases with disease severity, it is nearly impossible to analyse the prognostic impact of malnutrition alone. This can only be done in well-characterized settings where the analysis can be stratied according to disease severity. K. Norman et al. acute renal failure, pneumonia, respiratory failure, and infections after cardiac surgery.66 Impaired nutritional status results in impaired ventilatory drive and decreased respiratory muscle function6770 and is associated with an increased need for reventilation71 and with higher morbidity following lung volume reduction surgery for cancer72 or following thoracotomy for cancer.73 Weight loss over 10% in the preceding 6 months was also found to be a predictor of major postoperative complications in head and neck cancer patients.74 Preoperative nutritional status has also been reported to predict the severity of the systemic inammatory response syndrome after major vascular surgery.75 Recently, the phase angle, derived from bioelectrical impedance analysis and interpreted as an indicator of body cell mass and integrity, was shown to be an even better prognostic factor than the traditional nutritional markers (weight loss, SGA) for in-hospital complications in patients following gastrointestinal surgery76 and those with pancreatic77 or colon cancer.78 Morbidity in chronic disease Malnutrition is common in patients with severe congestive heart failure and is associated with increased right atrial pressure and tricuspid regurgitation.79 Patients with weight loss have a worse outcome when undergoing chemotherapy in gastrointestinal cancer.80 Malnourished patients with COPD8184 suffer a poorer prognosis than well-nourished patients. Malnutrition is also associated with poorer outcome in case of cancer, cardiovascular85 or gastrointestinal diseases.86 Morbidity in acute disease Malnutrition is frequent in orthopaedic patients33,34,87,88 and has been shown to result in a longer recovering time in women suffering from fractured neck of femur.89 Patients after acute stroke suffer signicantly more infections, bed sores,90 and poor functional outcome91 if they are malnourished. Taken together, malnutrition is associated with markedly increased morbidity in both acute and chronic disease.

Prevalence of malnutrition in hospital

Table 1 lists studies on the prevalence of hospital malnutrition since 1990. The wide range is probably not only due to the different medical or geographic settings but also to the different patient populations and the differing criteria used to diagnose malnutrition. It is obvious that the general prevalence of malnutrition has not changed during the last 15 years although the treatment of certain diseases has signicantly improved resulting in a better nutritional status (e.g. the reduced risk of wasting syndrome in HIV-infection in the area of highly active antiretroviral therapy (HAART). This observation of unchanged prevalence of malnutrition is probably due to the increasing average age of the hospital patients which might counterbalance medical progress. The weighted mean for European and US studies shows that approximately 31% of all hospital patients are considered malnourished or at nutritional risk.

Clinical implications of malnutrition

Impaired immune function, delayed wound healing, and convalescence from illness and decreased functional status are the main contributors for the enhanced morbidity in malnutrition.

Morbidity
Perioperative morbidity
Malnutrition signicantly affects convalescence following disease, surgery, or trauma. Wound healing is impaired in malnourished surgical patients.52,53 Studies have shown that the inammatory phase is prolonged, the proliferation of the broblasts, the collagen synthesis and the neoangiogenesis are reduced in malnutrition.54 Recent preoperative food intake has been reported to have a greater inuence on wound healing response than absolute losses of protein and fat from body stores.55 The relationship between malnutrition and the risks of major surgery has been studied extensively.7,5662 The degree of malnutrition correlates with the risk of infectious and noninfectious complications. Malnutrition is in general associated with a higher postoperative risk, in particular with the risk for nosocomial infections.63 Furthermore, malnutrition has been suggested as a risk factor for developing pressure ulcers.64 Malnutrition is associated with higher ICU stay and ventilation duration following liver transplantation65 as well as with postoperative complications such as

Functional impairment
A well-known consequence of malnutrition is muscle dysfunction as reected by a decreased grip strength.9295 The pathogenesis of muscle dysfunction in malnutrition is however not yet clearly understood. Handgrip strength correlates with the loss of total body protein60 and has been shown to be a good marker of immediate postoperative complications62,96,97 and predictive of major complications during 1 year in cirrhotic outpatients.98 Decreased handgrip strength is also a predictor of loss of functional status in hospitalised patients.99 In conclusion, malnutrition is associated with decreased muscle function and impaired functional status.

Length of hospital stay

Due to the increased morbidity, malnourished patients experience a signicantly prolonged treatment duration and length of hospital stay. Two recent studies analysing

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Prognostic impact of disease-related malnutrition 9

Table 2 Studies

Malnutrition is associated with an increased length of hospital stay. n Discipline Length of hospital stay (days) No malnutrition Malnutrition 20 15.6 43 20 8.9 16.7 10.2**/25.8*** 15**/17*** 17.2 po0.01 po0.01 po0.01 po0.01 po0.01 po0.01 po0.001 po0.001 p-value

Weinsier et al. (USA 1979)139 Robinson et al. (USA 1987)113 Cederholm et al. (Sweden 1995)132 Naber et al. (NL 1997)86 Edington et al. (UK 2000)138 Correira and Campos (ELAN 2003)2 Kyle et al. (Switzerland 2004)100 Pirlich et al. (Germany 2006)1 Weighted mean

134 100 205 155 850 9348 652 1886

General medicine General medicine Geriatrics Internal medicine Multidisciplinary Multidisciplinary Multidisciplinary Multidisciplinary

12 9.2 18 12.6 5.7 10.1 5.1 11 9.7

Normal nutritional status vs. moderate to severe ELAN, Latin America Nutrition Study.

**

***

malnutrition.

data from more than 1270 patients from two university hospitals in Geneva and Berlin demonstrated a close relationship between the degree of malnutrition and the length of hospital stay.100 A more detailed assessment of body composition with bioelectrical impedance analysis in 1707 patients with a BMI within the normal range has also shown that even patients with high fat mass but loss of fat free mass suffer a signicantly longer hospital stay which suggests that the body mass index alone is not a sensitive marker to detect nutritional depletion.101 Similarly, the recently published German hospital malnutrition study demonstrated in 1886 patients that the BMI is a poor predictor of LOS while malnutrition according to SGA was signicantly associated with increased LOS.1 This clearly indicates that the denition and or criteria of malnutrition inuence the associations between malnutrition and clinical outcome. According to the studies listed in Table 2, the average length of hospital stay in most studies is increased by 4070% in malnourished patients. However, when malnutrition is classied in subcategories (mild, moderate, and severe) the prolongation of LOS becomes even more impressive: in one study, patients assessed as severely malnourished according to NRI had a ve-fold increase of LOS compared to wellnourished patients.102

Cardiac cachexia, which has been dened as a loss of 46% of non-oedematous unintentional weight loss in the last 6 months,40 is a strong independent prognostic factor for mortality in chronic heart failure (CHF). It is more closely associated with hormonal changes in CHF, i.e. neurohormonal activation and catabolic/anabolic imbalance, than with measures of severity of CHF. The cachectic state has been proven to be predictive of 18-month mortality independent of age, New York Health Association class (NYHA class), peak oxygen consumption, and left ventricular ejection fraction.111 A worsening of nutritional status during hospital stay has repeatedly been reported and among elderly patients, malnutrition present at hospital discharge appears to be a strong independent risk factor for mortality in the subsequent 4.5 years.112 Table 3 lists disease settings in which an association between higher mortality and malnutrition has been demonstrated. Taken together, there is ample evidence that malnutrition is associated with increased mortality in both acute and chronic disease.

Economical implications
Due to the longer length of stay in hospital and more intensive treatment of malnourished patients, malnutrition has undeniably also become an economical issue (Figure 2). Robinson et al. demonstrated that patients with an impaired nutritional status on admission to hospital experienced a 30% increase of hospital stay.113 This was associated with a doubling of the costs, even though the patients had the same disease-related group (DRG) and therefore the same reimbursement. A recent study from South America even reported an increase of treatment costs by 300%.114 Inappropriate reimbursement despite more time and cost intensive treatment of malnourished patients was also demonstrated by Reilly et al.115 and more recently by our group116 where we showed that malnourished patients can be detected with a structured assessment and

Mortality
A close relationship between malnutrition and increased mortality has been demonstrated in chronic disease such as HIV/AIDS,42 chronic liver disease,38,103 terminal renal insufciency,41,104,105 cancer,36,106 and COPD107; but also in acute settings such as stroke and hip fracture89,91 as well as following lung resection,72 thoracotomy,73 cardiac surgery,66 and lung108 or liver transplantation,39 malnutrition has been shown to increase mortality. Malnourished patients in an intensive care unit have a poorer prognosis and survival.109 A low BMI has been described as independent predictor of shortened survival in hospitalised elderly.110

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10 K. Norman et al.

Table 3 Disease

Association between malnutrition and mortality according to different diseases in acute and chronic settings. Author Nutritional variables

Chronic disease Organ failure Liver cirrhosis Chronic liver disease (following LTX) Terminal renal insufciency Chronic heart failure

Caregaro et al. 103 Selberg et al. 39 De Lima et al. 104 Anker et al.
40

TSF, MAMC Patients with a deviation of measured from predicted REE 4+20% and a BCMo35% of body weight had reduced survival after LTX (5-year survival rate, 54%) Signicantly lower albumin (3.370.9 vs. 4.070.5 g/dL) in the patients who died within 90 days vs. patients with 10-year survival (retrospective multivariate analysis) The cachectic stateas dened by non-intentional documented weight loss of at least 7.5% of previous normal weightwas predictive of 18-month mortality independent of age, NYHA class, left-ventricular ejection fraction, and peak oxygen consumption. Mortality in the cachectic patients was 18% at 3 months, 29% at 6 months, 39% at 12 months, and 50% at 18 months (Cox proportionalhazards model) In patients with a pre-transplant BMIo17 kg/m2 or 425 kg/m2 the risk of dying within 90 days post-transplant was increased (OR 3.7; p 0.085) 410% of habitual body weight as well as low BMI was signicantly related to decreased survival (po0.005; Cox proportional-hazards model) Combination of TSF, AMC, albumin, transferrin, malnourished patients (index o40) 14 months survival vs. 57 months (multivariate) Malnutrition (height/weight z-score) was the most signicant adverse factor affecting duration of complete remission in a Coxs multivariate model. Children with height for age z-score o2 had a relapse risk of 8.2 (95% condence interval 3.121.9) relative to children with z-score 42 Patients who died within 6 months after diagnosis had signicantly lower values of all nutritional parameters (weight/height, TSF, MUAC, albumin, transferrin, creatinine index, and TLC) than those who survived more than 6 months Malnutrition according to the NRI, correlated with mortality rates with a postoperative mortality rate of 33.3% in the severely malnourished group and 6.5% in the moderate group. In weight loss was greater in those patients who died than in those who survived (p 0.06) Patients with phase angle o5.01 had a signicantly shorter median survival time of 6.3 months (95% CI 3.5, 9.2), than those with phase angle 45.01 who had a median survival time of 10.2 months (95% CI 9.6, 10.8); (p 0.02) Patients with a phase angle p5.57 had a signicantly shorter median survival of 8.6 months (95% CI: 4.8, 12.4), than those with a phase angle 45.57 who had a median survival of 40.4 months (95% CI: 21.9, 58.8; p 0.0001) KaplanMeier analyses revealed a signicantly prolonged survival in patients with a BCM 430% of body weight assessed by BIA or serum albumin levels exceeding 30 g/L (PCM score percentage ideal weight, TSF, MAMC, creatinine height index, albumin, transferring, TLC, DCHS) 1 month survival increased from 2% (mild PCM) to 57% (severe PCM) (po0.001), 6-month survival from 7% to 67% (po0.001) and 12-month survival from 14% to 76% (po0.001) A low TSF was associated with increased hospital stay, death and readmission within 6 months of discharge Serum albumin concentration in the hospital was a strong and independent predictor of mortality at 3 months after acute stroke [hazard ratio 0.91 (95% CI: 0.84, 0.99) for a 1 g/L higher serum albumin concentration]

Lung transplantation Chronic obstructive pulmonary disease Malignant disease Lymphoma Acute lymphatic leukaemiay

Madill et al.
108

Schols et al.
140

Aviles et al.
106

Viana et al.
141

Lung cancer

Lai and Perng142 Rey Ferro et al. 143

Gastric cancer

Pancreatic cancer

Gupta et al.
77

Colon cancer

Gupta et al.
78

Others HIV/AIDS

Suttmann et al. 42

Acute disease Alcoholic hepatitis

Mendenhall et al. 144

Community acquired pneumonia Stroke

Hedlund et al. 145 Gariballa et al. 91

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Prognostic impact of disease-related malnutrition
Table 3 (continued ) Disease Critically ill Author Giner et al.
109

11

Nutritional variables Death in hospital was higher in the malnourished group (low albumin and weight/height ratio) than in the well-nourished group (31% vs. 20%, respectively; po0.05) as well as complications rate 40% in the well-nourished vs. 55% in the malnourished (po0.01)

Note the variety of nutritional parameters used as criterion for the diagnosis of malnutrition. NRI, Nutritional Risk Index; PCM, Protein Calorie Malnutrition (BLACKBURN 1977); TSF, triceps skinfold; MUAC, mid upper arm circumference; MAMC, mid arm muscle circumference; BMI, body mass index; BCM BIA, body cell mass in % of body weight assessed with bioelectrical impedance analysis; TLC, total lymphocyte count; Hb, haemoglobin; Hct, haematocrit. LTX, liver transplantation; NYHA, New York Heart Association; DCHS, delayed cutaneous hypersensitivity Prognosis after liver transplantation resp. surgical intervention. y After chemotherapy.

Malnutrition

Morbidity wound healing infections complications convalescence

Mortality

it substantially reduced treatment cost of postoperative complications.123126 Braga et al. calculated that preoperative immunonutrition reduced total costs by approximately 50%.123 However, there is a lack of recent prospective data on cost containment through nutritional intervention in Europe.

Treatment

Conclusion
Malnutrition is common in sick subjects (especially hospital patients) but is frequently not recognised or underestimated. Malnutrition increases morbidity and mortality in acute and chronic diseases, impairs recovery and convalescence, prolongs treatment duration, and increases treatment costs. Since it has been demonstrated that proper nutritional care can reduce the prevalence of hospital malnutrition and costs, nutritional assessment should be part of every medical examination in order to recognise malnutrition early and initiate timely nutritional therapy. Unfortunately, only a fraction of malnourished patients receives nutritional therapy due to a lack of awareness of the malnutrition-related adverse effects. Improved education of medical staff is needed and screening for malnutrition is mandatory.

Length of hospital stay

COSTS

QUALITY OF LIFE

Figure 2 Prognostic impact of malnutrition. Malnutrition affects morbidity by impaired wound healing and immune system with increased rate of infectious and non-infectious complication rate and a general impairment of convalescence. The increased morbidity results in increased mortality, duration and intensity of treatment, and length of hospital stay. It is obvious that these consequences of malnutrition result in increased treatment costs.

documentation of nutritional status and this is partly reected in the G-DRG/ICD 10 system. This is in contrast to the results of trials that showed that the prevalence of malnutrition can be reduced by proper nutritional care117 and that nutritional therapy in malnourished patients resulted in a signicant reduction of length of stay by approximately 2.5 days in average and treatment costs.118,119 Already 10 years ago, Tucker concluded in his review that nutritional intervention results in approximately $8300 cost savings per bed and per year.118 Several studies have also investigated the benets and cost effectiveness of immunonutrition and have demonstrated that early enteral nutrition with an immune enhancing formula in critically ill results in a signicant reduction in morbidity,120 decreased hospital stay, and signicantly reduced frequency of infections121 as well as mortality.122 When administered pre-, peri-, or postoperatively, immunonutrition was shown to be cost effective since

Conict of interest statement

None declared.

Acknowledgements
We thank Baxter Deutschland GmbH (Erlangen, Germany) and the Foundation Nutrition 2000Plus (Switzerland) for their nancial support.

References
1. Pirlich M, Schutz T, Norman K, Gastell S, Lubke HJ, Bischoff SC, et al. The German hospital malnutrition study. Clin Nutr 2006;25:56372.

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12
2. Correia MI, Campos AC. Prevalence of hospital malnutrition in Latin America: the multicenter ELAN study. Nutrition 2003; 19:8235. 3. McWhirter JP, Pennington CR. Incidence and recognition of malnutrition in hospital. BMJ 1994;308:9458. 4. Rasmussen HH, Kondrup J, Staun M, Ladefoged K, Kristensen H, Wengler A. Prevalence of patients at nutritional risk in Danish hospitals. Clin Nutr 2004;23:100915. 5. Kinosian B, Jeejeebhoy KN. What is malnutrition? Does it matter? Nutrition 1995;11:1967. 6. Lochs H, Allison SP, Meier R, Pirlich M, Kondrup J, Schneider S, et al. Introductory to the ESPEN Guidelines on enteral nutrition: terminology, denitions and general topics. Clin Nutr 2006;25:1806. 7. Windsor JA, Hill GL. Weight loss with physiologic impairment. A basic indicator of surgical risk. Ann Surg 1988;207:2906. 8. Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker S, Mendelson RA, et al. What is subjective global assessment of nutritional status? J Parenter Enteral Nutr 1987;11: 813. 9. Buzby GP, Knox LS, Crosby LO, Eisenberg JM, Haakenson CM, McNeal GE, et al. Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients. Am J Clin Nutr 1988;47:36681. 10. Vellas B, Guigoz Y, Garry PJ, Nourhashemi F, Bennahum D, Lauque S, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition 1999;15:11622. 11. Malnutrition Advisory Group (MAG). MAGguidelines for detection and management of malnutrition. Redditch UK: British Association for Parenteral and Enteral Nutrition; 2000. 12. Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr 2003;22:32136. 13. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M. ESPEN guidelines for nutrition screening 2002. Clin Nutr 2003;22: 41521. 14. Kyle UG, Kossovsky MP, Karsegard VL, Pichard C. Comparison of tools for nutritional assessment and screening at hospital admission: a population study. Clin Nutr 2006;25:40917. 15. Campbell IT. Limitations of nutrient intake. The effect of stressors: trauma, sepsis and multiple organ failure. Eur J Clin Nutr 1999;53(Suppl. 1):S1437. 16. Tisdale MJ. Molecular pathways leading to cancer cachexia. Physiology (Bethesda) 2005;20:3408. 17. Deans DA, Wigmore SJ, Gilmour H, Tisdale MJ, Fearon KC, Ross JA. Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy. Br J Cancer 2006;94:7316. 18. Bing C, Bao Y, Jenkins J, Sanders P, Manieri M, Cinti S, et al. Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc Natl Acad Sci USA 2004;101:25005. 19. Islam-Ali B, Khan S, Price SA, Tisdale MJ. Modulation of adipocyte G-protein expression in cancer cachexia by a lipidmobilizing factor (LMF). Br J Cancer 2001;85:75863. 20. Markson EW. Functional, social, and psychological disability as causes of loss of weight and independence in older communityliving people. Clin Geriatr Med 1997;13:63952. 21. Morley JE. Anorexia of aging: physiologic and pathologic. Am J Clin Nutr 1997;66:76073. 22. Anker SD, John M, Pedersen PU, Raguso C, Cicoira M, Dardai E, et al. ESPEN guidelines on enteral nutrition: cardiology and pulmonology. Clin Nutr 2006;25:3118. 23. Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, et al. ESPEN guidelines on enteral nutrition: non-surgical oncology. Clin Nutr 2006;25:24559.

K. Norman et al.
24. Cano N, Fiaccadori E, Tesinsky P, Toigo G, Druml W, Kuhlmann M, et al. ESPEN guidelines on enteral nutrition: adult renal failure. Clin Nutr 2006;25:295310. 26. Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, et al. ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr 2006;25:21023. 27. Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schutz T, et al. ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr 2006;25:26074. 28. Meier R, Ockenga J, Pertkiewicz M, Pap A, Milinic N, Mace J, et al. ESPEN guidelines on enteral nutrition: pancreas. Clin Nutr 2006;25:27584. 29. Ockenga J, Grimble R, Jonkers-Schuitema C, Macallan D, Melchior JC, Sauerwein HP, et al. ESPEN guidelines on enteral nutrition: wasting in HIV and other chronic infectious diseases. Clin Nutr 2006;25:31929. 30. Plauth M, Cabre E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, et al. ESPEN guidelines on enteral nutrition: liver disease. Clin Nutr 2006;25:28594. 31. Volkert D, Berner YN, Berry E, Cederholm T, Coti BP, Milne A, et al. ESPEN guidelines on enteral nutrition: geriatrics. Clin Nutr 2006;25:33060. 32. Pirlich M, Schutz T, Kemps M, Luhman N, Minko N, Lubke HJ, et al. Social risk factors for hospital malnutrition. Nutrition 2005;21:295300. 33. Hedstrom M. Hip fracture patients, a group of frail elderly people with low bone mineral density, muscle mass and IGF-I levels. Acta Physiol Scand 1999;167:34750. 34. Ponzer S, Tidermark J, Brismar K, Soderqvist A, Cederholm T. Nutritional status, insulin-like growth factor-1 and quality of life in elderly women with hip fractures. Clin Nutr 1999;18:2416. 35. Neumann SA, Miller MD, Daniels L, Crotty M. Nutritional status and clinical outcomes of older patients in rehabilitation. J Hum Nutr Diet 2005;18:12936. 36. DeWys W. Weight loss and nutritional abnormalities in cancer patients: incidence, severity and signicance. In: Calman C, Fearon KC, editors. Nutritional support for the cancer patient. London: W.B. Saunders; 1986. p. 25161. 37. Muller MJ. Malnutrition in cirrhosis. J Hepatol 1995;23 (Suppl. 1):315. 38. Alberino F, Gatta A, Amodio P, Merkel C, Di Pascoli L, Boffo G, et al. Nutrition and survival in patients with liver cirrhosis. Nutrition 2001;17:44550. 39. Selberg O, Bottcher J, Tusch G, Pichlmayr R, Henkel E, Muller MJ. Identication of high- and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology 1997; 25:6527. 40. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, WebbPeploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet 1997;349:10503. 41. Lawson JA, Lazarus R, Kelly JJ. Prevalence and prognostic signicance of malnutrition in chronic renal insufciency. J Ren Nutr 2001;11:1622. 42. Suttmann U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, Muller MJ. Incidence and prognostic value of malnutrition and wasting in human immunodeciency virus-infected outpatients. J Acquir Immune Dec Syndr Hum Retrovirol 1995;8: 23946. 43. Cano NJ, Roth H, Court-Fortune I, Cynober L, GerardBoncompain M, Cuvelier A, et al. Nutritional depletion in patients on long-term oxygen therapy and/or home mechanical ventilation. Eur Respir J 2002;20:307. 44. Cano NJ, Pichard C, Roth H, Court-Fortune I, Cynober L, Gerard-Boncompain M, et al. C-reactive protein and body mass index predict outcome in end-stage respiratory failure. Chest 2004;126:5406.

ARTICLE IN PRESS
Prognostic impact of disease-related malnutrition
45. Grand RJ. Malnutrition and inammatory bowel disease. Curr Concepts Nutr 1980;9:12540. 46. Roulet M. Protein-energy malnutrition in cystic brosis patients. Acta Paediatr Suppl 1994;83:438. 47. Cameron A, Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Curr Opin Clin Nutr Metab Care 2002;5:63143. 48. Dupertuis YM, Kossovsky MP, Kyle UG, Raguso CA, Genton L, Pichard C. Food intake in 1707 hospitalised patients: a prospective comprehensive hospital survey. Clin Nutr 2003;22: 11523. 49. Kondrup J, Johansen N, Plum LM, Bak L, Larsen IH, Martinsen A, et al. Incidence of nutritional risk and causes of inadequate nutritional care in hospitals. Clin Nutr 2002;21:4618. 50. Incalzi RA, Gemma A, Capparella O, Cipriani L, Landi F, Carbonin P. Energy intake and in-hospital starvation. A clinically relevant relationship. Arch Intern Med 1996;156: 4259. 51. Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly hospitalized patients: a prospective study. JAMA 1999;281:20139. 52. Haydock DA, Hill GL. Impaired wound healing in surgical patients with varying degrees of malnutrition. J Parenter Enteral Nutr 1986;10:5504. 53. Rai J, Gill SS, Kumar BR. The inuence of preoperative nutritional status in wound healing after replacement arthroplasty. Orthopedics 2002;25:41721. 54. Waldorf H, Fewkes J. Wound healing. Adv Dermatol 1995;10: 7796. 55. Windsor JA, Knight GS, Hill GL. Wound healing response in surgical patients: recent food intake is more important than nutritional status. Br J Surg 1988;75:1357. 56. Mullen JL, Buzby GP, Waldman MT, Gertner MH, Hobbs CL, Rosato EF. Prediction of operative morbidity and mortality by preoperative nutritional assessment. Surg Forum 1979;30: 802. 57. Mullen JL, Gertner MH, Buzby GP, Goodhart GL, Rosato EF. Implications of malnutrition in the surgical patient. Arch Surg 1979;114:1215. 58. Mullen JL, Buzby GP, Matthews DC, Smale BF, Rosato EF. Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support. Ann Surg 1980;192:60413. 59. Nakamura K, Moriyama Y, Kariyazono H, Hamada N, Toyohira H, Taira A, et al. Inuence of preoperative nutritional state on inammatory response after surgery. Nutrition 1999;15: 83441. 60. Windsor JA, Hill GL. Grip strength: a measure of the proportion of protein loss in surgical patients. Br J Surg 1988;75:8802. 61. Windsor JA. Underweight patients and the risks of major surgery. World J Surg 1993;17:16572. 62. Webb AR, Newman LA, Taylor M, Keogh JB. Hand grip dynamometry as a predictor of postoperative complications reappraisal using age standardized grip strengths. J Parenter Enteral Nutr 1989;13:303. 63. Schneider SM, Veyres P, Pivot X, Soummer AM, Jambou P, Filippi J, et al. Malnutrition is an independent factor associated with nosocomial infections. Br J Nutr 2004;92: 10511. 64. Breslow R. Nutritional status and dietary intake of patients with pressure ulcers: review of research literature 1943 to 1989. Decubitus 1991;4:1621. 65. Pikul J, Sharpe MD, Lowndes R, Ghent CN. Degree of preoperative malnutrition is predictive of postoperative morbidity and mortality in liver transplant recipients. Transplantation 1994;57:46972. 66. Abel RM, Fischer JE, Buckley MJ, Barnett GO, Austen WG. Malnutrition in cardiac surgical patients. Results of a prospec-

13
tive, randomized evaluation of early postoperative parenteral nutrition. Arch Surg 1976;111:4550. Arora NS, Rochester DF. Respiratory muscle strength and maximal ventilatory ventilation in undernourished patients. Am Rev Respir Dis 1982;126:58. Askanazi J, Weissmann C, La Sala PA. Effect of protein intake on ventilatory drive. Anesthestiology 1984;60:10610. Pieters T, Boland B, Beguin C, Veriter C, Stanescu D, Frans A, et al. Lung function study and diffusion capacity in anorexia nervosa. J Intern Med 2000;248:13742. Sheldon GF, Petersen S. R. Malnutrition and cardiopulmonary function: relation to oxygen transport. J Parenter Enteral Nutr 1980;4:37683. Jagoe RT, Goodship TH, Gibson GJ. The inuence of nutritional status on complications after operations for lung cancer. Ann Thorac Surg 2001;71:93643. Mazolewski P, Turner JF, Baker M, Kurtz T, Little AG. The impact of nutritional status on the outcome of lung volume reduction surgery: a prospective study. Chest 1999;116:6936. Bashir Y, Graham TR, Torrance A, Gibson GJ, Corris PA. Nutritional state of patients with lung cancer undergoing thoracotomy. Thorax 1990;45:1836. van Bokhorst-de van der Schueren MA, van Leeuwen PA, Sauerwein HP, Kuik DJ, Snow GB, Quak JJ. Assessment of malnutrition parameters in head and neck cancer and their relation to postoperative complications. Head Neck 1997;19: 41925. Hassen TA, Pearson S, Cowled PA, Fitridge RA. Preoperative nutritional status predicts the severity of the Systemic Inammatory Response Syndrome (SIRS) following major vascular surgery. Eur J Vasc Endovasc Surg 2007;33:696702. Barbosa-Silva MC, Barros AJ. Bioelectric impedance and individual characteristics as prognostic factors for postoperative complications. Clin Nutr 2005;24:8308. Gupta D, Lis CG, Dahlk SL, Vashi PG, Grutsch JF, Lammersfeld CA. Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer. Br J Nutr 2004;92: 95762. Gupta D, Lammersfeld CA, Burrows JL, Dahlk SL, Vashi PG, Grutsch JF, et al. Bioelectrical impedance phase angle in clinical practice: implications for prognosis in advanced colorectal cancer. Am J Clin Nutr 2004;80:16348. Carr JG, Stevenson LW, Walden JA, Heber D. Prevalence and hemodynamic correlates of malnutrition in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1989;63:70913. Andreyev HJN, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer 1998;34:5039. Braun SR, Dixon RM, Keim NL, Luby M, Anderegg A, Shrago ES. Predictive clinical value of nutritional assessment factors in COPD. Chest 1984;85:3537. Engelen MP, Schols AM, Baken WC, Wesseling GJ, Wouters EF. Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD. Eur Respir J 1994;7:17937. Knowles JB, Fairbarn MS, Wiggs BJ, Chan-Yan C, Pardy RL. Dietary supplementation and respiratory muscle performance in patients with COPD. Chest 1988;93:97783. Schols AM, Soeters PB, Dingemans AM, Mostert R, Frantzen PJ, Wouters EF. Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147:11516. Edington J, Winter PD, Coles SJ, Gale CR, Martyn CN. Outcomes of undernutrition in patients in the community with cancer or cardiovascular disease. Proc Nutr Soc 1999;58: 65561.

67.

68. 69.

70.

71.

72.

73.

74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

85.

ARTICLE IN PRESS
14
86. Naber TH, Schermer T, de Bree A, Nusteling K, Eggink L, Kruimel JW, et al. Prevalence of malnutrition in nonsurgical hospitalized patients and its association with disease complications. Am J Clin Nutr 1997;66:12329. 87. Bachrach-Lindstrom M, Unosson M, Ek AC, Arnqvist HJ. Assessment of nutritional status using biochemical and anthropometric variables in a nutritional intervention study of women with hip fracture. Clin Nutr 2001;20:21723. 88. Galvard H, Elmstahl S, Elmstahl B, Samuelsson SM, Robertsson E. Differences in body composition between female geriatric hip fracture patients and healthy controls: body fat is more important as explanatory factor for the fracture than body weight and lean body mass. Aging (Milano) 1996;8:2826. 89. Bastow MD, Rawlings J, Allison SP. Benets of supplementary tube feeding after fractured neck of femur: a randomised controlled trial. Br Med J (Clin Res Ed) 1983;287:158992. 90. Davalos A, Ricart W, Gonzalez-Huix F, Soler S, Marrugat J, Molins A, et al. Effect of malnutrition after acute stroke on clinical outcome. Stroke 1996;27:102832. 91. Gariballa SE, Parker SG, Taub N, Castleden CM. Inuence of nutritional status on clinical outcome after acute stroke. Am J Clin Nutr 1998;68:27581. 92. Norman K, Schutz T, Kemps M, Josef LH, Lochs H, Pirlich M. The Subjective Global Assessment reliably identies malnutritionrelated muscle dysfunction. Clin Nutr 2005;24:14350. 93. Russell DM, Prendergast PJ, Darby PL, Garnkel PE, Whitewell J, Jeejeebhoy KN. A comparison between muscle function and body composition in anorexia nervosa: the effect of refeeding. Am J Clin Nutr 1983;38:22937. 94. Lennmarken C, Larsson J. Skeletal muscle function and energy metabolites in malnourished surgical patients. Acta Chir Scand 1986;152:16973. 95. Vaz M, Thangam S, Prabhu A, Shetty PS. Maximal voluntary contraction as a functional indicator of adult chronic undernutrition. Br J Nutr 1996;76:915. 96. Klidjian AM, Foster KJ, Kammerling RM, Cooper A, Karran SJ. Relation of anthropometric and dynamometric variables to serious postoperative complications. Br Med J 1980;281: 899901. 97. Pettigrew RA, Burns HJG, Carter DC. Evaluating surgical risk: the importance of technical factors in determining outcome. Br J Surg 1987;74:791. 98. Alvares-da-Silva MR, Reverbel DS. Comparison between handgrip strength, subjective global assessment, and prognostic nutritional index in assessing malnutrition and predicting clinical outcome in cirrhotic outpatients. Nutrition 2005;21: 1137. 99. Humphreys J, de la MP, Hirsch S, Barrera G, Gattas V, Bunout D. Muscle strength as a predictor of loss of functional status in hospitalized patients. Nutrition 2002;18:61620. 100. Kyle UG, Pirlich M, Schuetz T, Lochs H, Pichard C. Is nutritional depletion by Nutritional Risk Index associated with increased length of hospital stay? A population-based study. J Parenter Enteral Nutr 2004;28:99104. 101. Kyle UG, Pirlich M, Lochs H, Schuetz T, Pichard C. Increased length of hospital stay in underweight and overweight patients at hospital admission: a controlled population study. Clin Nutr 2005;24:13342. 102. Kyle UG, Schneider SM, Pirlich M, Lochs H, Hebuterne X, Pichard C. Does nutritional risk, as assessed by Nutritional Risk Index, increase during hospital stay? A multinational population-based study. Clin Nutr 2005;24:51624. 103. Caregaro L, Alberino F, Amodio P, Merkel C, Bolognesi M, Angeli P, et al. Malnutrition in alcoholic and virus-related cirrhosis. Am J Clin Nutr 1996;63:6029. 104. De Lima JJ, da Fonseca JA, Godoy AD. Baseline variables associated with early death and extended survival on dialysis. Ren Fail 1998;20:5817.

K. Norman et al.
105. Kushner RF, de Vries PM, Gudivaka R. Use of bioelectrical impedance analysis measurements in the clinical management of patients undergoing dialysis. Am J Clin Nutr 1996;64: 503S9S. 106. Aviles A, Yanez J, Lopez T, Garcia EL, Guzman R, Diaz-Maqueo JC. Malnutrition as an adverse prognostic factor in patients with diffuse large cell lymphoma. Arch Med Res 1995;26:314. 107. Soler-Cataluna JJ, Sanchez-Sanchez L, Martinez-Garcia MA, Sanchez PR, Salcedo E, Navarro M. Mid-arm muscle area is a better predictor of mortality than body mass index in COPD. Chest 2005;128:210815. 108. Madill J, Gutierrez C, Grossman J, Allard J, Chan C, Hutcheon M, et al. Nutritional assessment of the lung transplant patient: body mass index as a predictor of 90-day mortality following transplantation. J Heart Lung Transplant 2001;20:28896. 109. Giner M, Laviano A, Meguid MM, Gleason JR. In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists. Nutrition 1996;12:239. 110. Landi F, Onder G, Gambassi G, Pedone C, Carbonin P Bernabei R. , Body mass index and mortality among hospitalized patients. Arch Intern Med 2000;160:26414. 111. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation 1997;96:52634. 112. Sullivan DH, Walls RC. Protein-energy undernutrition and the risk of mortality within six years of hospital discharge. J Am Coll Nutr 1998;17:5718. 113. Robinson G, Goldstein M, Levine GM. Impact of nutritional status on DRG length of stay. J Parenter Enteral Nutr 1987;11: 4951. 114. Correia MI, Waitzberg DL. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr 2003;22:2359. 115. Reilly Jr. JJ, Hull SF, Albert N, Waller A, Bringardener S. Economic impact of malnutrition: a model system for hospitalized patients. J Parenter Enteral Nutr 1988;12:3716. 116. Ockenga J, Freudenreich M, Zakonsky R, Norman K, Pirlich M, Lochs H. Nutritional assessment and management in hospitalised patients: implication for DRG-based reimbursement and health care quality. Clin Nutr 2005;24:9139. 117. OFlynn J, Peake H, Hickson M, Foster D, Frost G. The prevalence of malnutrition in hospitals can be reduced: results from three consecutive cross-sectional studies. Clin Nutr 2005; 24:107888. 118. Tucker HN, Miguel SG. Cost containment through nutritional intervention. Nutr Rev 1996;54:11121. 119. Kruizenga HM, Van Tulder MW, Seidell JC, Thijs A, Ader HJ, Van Bokhorst-de van der Schueren MA. Effectiveness and costeffectiveness of early screening and treatment of malnourished patients. Am J Clin Nutr 2005;82:10829. 120. Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guys Hospital Intensive Care Group. Crit Care Med 1998;26:116472. 121. Bower RH, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and sh oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med 1995; 23:43649. 122. Galban C, Montejo JC, Mesejo A, Marco P, Celaya S, SanchezSegura JM, et al. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med 2000;28:6438. 123. Braga M, Gianotti L. Preoperative immunonutrition: costbenet analysis. J Parenter Enteral Nutr 2005;29:S5761.

ARTICLE IN PRESS
Prognostic impact of disease-related malnutrition
124. Gianotti L, Braga M, Frei A, Greiner R, Di CV. Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition. Shock 2000;14: 32530. 125. Senkal M, Mumme A, Eickhoff U, Geier B, Spath G, Wulfert D, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med 1997;25:148996. 126. Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg 1999;134:130916. 127. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:52532. 128. Coats KG, Morgan SL, Bartolucci AA, Weinsier RL. Hospitalassociated malnutrition: a reevaluation 12 years later. J Am Diet Assoc 1993;93:2733. 129. Lansey S, Waslien C, Mulvihill M, Fillit H. The role of anthropometry in the assessment of malnutrition in the hospitalized frail elderly. Gerontology 1993;39:34653. 130. Mowe M, Bohmer T, Kindt E. Reduced nutritional status in an elderly population is probable in before disease and possible contributes to the development of disease. Am J Clin Nutr 1994;59:31724. 131. Larsson J, Akerlind I, Permerth J, Hornqvist JO. The relation between nutritional state and quality of life in surgical patients. Eur J Surg 1994;160:32934. 132. Cederholm T, Jagren C, Hellstrom K. Outcome of proteinenergy malnutrition in elderly medical patients. Am J Med 1995;98:6774. 133. Waitzberg DL, Caiaffa WT, Correia MI. Hospital malnutrition: the Brazilian national survey (IBRANUTRI): a study of 4000 patients. Nutrition 2001;17:57380. 134. Bruun LI, Bosaeus I, Bergstad I, Nygaard K. Prevalence of malnutrition in surgical patients: evaluation of nutritional support and documentation. Clin Nutr 1999;18:1417. 135. Corish CA, Flood P, Mulligan S, Kennedy NP. Apparent low frequency of undernutrition in Dublin hospital in- patients:

15
should we review the anthropometric thresholds for clinical practice? Br J Nutr 2000;84:32535. Kyle UG, Pirlich M, Schuetz T, Luebke HJ, Lochs H, Pichard C. Prevalence of malnutrition in 1760 patients at hospital admission: a controlled population study of body composition. Clin Nutr 2003;22:47381. Wyszynski DF, Perman M, Crivelli A. Prevalence of hospital malnutrition in Argentina: preliminary results of a populationbased study. Nutrition 2003;19:1159. Edington J, Boorman J, Durrant ER, Perkins A, Gifn CV, James R, et al. Prevalence of malnutrition on admission to four hospitals in England. The Malnutrition Prevalence Group. Clin Nutr 2000;19:1915. Weinsier RL, Hunker EM, Krumdieck CL, Butterworth Jr. CE. Hospital malnutrition. A prospective evaluation of general medical patients during the course of hospitalization. Am J Clin Nutr 1979;32:41826. Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157: 17917. Viana MB, Murao M, Ramos G, Oliveira HM, de Carvalho RI, de Bastos M, et al. Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis. Arch Dis Child 1994;71:30410. Lai SL, Perng RP. Impact of nutritional status on the survival of lung cancer patients. Zhonghua Yi Xue Za Zhi (Taipei) 1998; 61:13440. Rey-Ferro M, Castano R, Orozco O, Serna A, Moreno A. Nutritional and immunologic evaluation of patients with gastric cancer before and after surgery. Nutrition 1997;13: 87881. Mendenhall CL, Tosch T, Weesner RE, Garcia-Pont P, Goldberg SJ, Kiernan T, et al. VA cooperative study on alcoholic hepatitis. II: Prognostic signicance of proteincalorie malnutrition. Am J Clin Nutr 1986;43:2138. Hedlund J, Hansson LO, Ortqvist A. Short- and long-term prognosis for middle-aged and elderly patients hospitalized with community-acquired pneumonia: impact of nutritional and inammatory factors. Scand J Infect Dis 1995;27:327.

136.

137.

138.

139.

140.

141.

142.

143.

144.

145.