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Summary: Rationale: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. Methods: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face‐to‐face meetings, telephone conferences, and e‐mail communications. Results: A two‐step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology‐related diagnosis categories. Conclusion: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re‐considered every 3–5 years. [ABSTRACT FROM AUTHOR]

Background/Objectives:Intravenous (i.v.) glutamine supplementation of parenteral nutrition (PN) can improve clinical outcomes, reduce mortality and infection rates and shorten the length of hospital and/or intensive care unit (ICU) stays compared with standard PN. This study is a pharmacoeconomic analysis to determine whether i.v. glutamine supplementation of PN remains both a highly favourable and cost-effective option for Italian ICU patients.Subjects/Methods:A previously published discrete event simulation model was updated by incorporating the most up-to-date and clinically relevant efficacy data (a clinically realistic subgroup analysis from a published meta-analysis), recent cost data from the Italian health-care system and the latest epidemiology data from a large Italian ICU database (covering 230 Italian ICUs and more than 77 000 patients). Sensitivity analyses were performed to test the robustness of the results.Results:Parenteral glutamine supplementation can significantly improve ICU efficiency in Italy, as the additional cost of supplemented treatment is more than completely offset by cost savings in hospital care. Supplementation was more cost-effective (cost-effectiveness ratio (CER)=[euro ]35 165 per patient discharged alive) than standard, non-supplemented PN (CER=[euro ]40 156 per patient discharged alive), and it resulted in mean cost savings of [euro ]4991 per patient discharged alive or [euro ]1047 per patient admitted to the hospital. Sensitivity analyses confirmed the robustness of these results.Conclusions:Alanyl-glutamine supplementation of PN is a clinically and economically attractive strategy for ICU patients in Italy and may be applicable to selected ICU patient populations in other countries. [ABSTRACT FROM AUTHOR]

Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia-cachexia syndrome. This condition has a negative impact upon patients' nutritional status. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients' nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named "parallel pathway", has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The "parallel pathway" implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey. [ABSTRACT FROM AUTHOR]

Background/Objectives:Disease-related malnutrition is a common comorbidity at hospital admission. The purpose of the present report was to describe the data on nutritional care routines collected during the Project: Iatrogenic MAlnutrition in Italy (PIMAI) study, as these may be helpful to avoid iatrogenic malnutrition and improve nutritional policies.Subjects/Methods:Standards of nutritional care were assessed on the basis of (1) adherence to study protocol (completeness of data collected); (2) attitude in assessing the nutritional status; (3) prescription of nutritional therapy (within 3 days) at least in patients presenting with overt malnutrition (body mass index (BMI) <18.5 kg/m2 or significant weight loss (10% in 3 months and/or 5% in the last month)), regardless of its adequacy, and adherence to current guidelines and (4) attitude in monitoring nutritional status during the stay (number of weight measurements performed compared with those expected).Results:In total, 1583 subjects were assessed. A minimum data set for performing the Nutritional Risk Screening 2002 tool was available in 1284 patients (81.1%), but nutritional screening was possible in every patient by alternative analytical criteria related to food intake, anthropometry and biochemistry. However, several missing values were recorded, particularly in biochemical parameters due to lack of prescription by admission wards. According to ward practices, only 38.2% of the patients had the BMI calculated. A nutritional support was prescribed only to 26/191 patients (13.6%) presenting with overt malnutrition. Finally, we recorded that only 21.6% of the patients (207/960 were randomly selected) had their weight monitored on a scheduled basis. This reality was worse in surgical rather than medical departments (17 vs 26%; P<0.001).Conclusion:Present results confirm that in Italy, nutritional care routines are still poor and need improvements. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is an important pathogenetic mechanism in several diseases, and antioxidant supplementation may reduce morbidity and mortality. The aim of this review is to focus on the role of oxidative stress in the pathogenesis and clinical outcome of critical illness, cancer, and neurological disorders and to evaluate the efficacy of antioxidant supplementation on morbidity and mortality in these conditions. Methods: We reviewed the literature on reactive oxygen species and antioxidants in critically ill, neurological, and neoplastic patients. Results and conclusions: Clinical and experimental evidence demonstrates that oxidative stress and/or antioxidant deficiency contribute to morbidity and mortality in critically ill, neurological, and cancer patients. Nutritional and pharmacological approaches to modulate oxidative stress are beneficial in improving clinical outcome in critically ill (especially respiratory distress syndrome) patients. In contrast, antioxidant supplementation does not substantially reduce the risk of cancer in clinical trials and paradoxically beta carotene has been shown to increase cancer risk in heavy smokers. Increased reactive oxygen species production may be exploited to induce apoptosis and to cure selected types of cancer. In dementia, modulation of oxidative stress by vitamin E administration has failed to provide clinical benefits; other oral antioxidants (lipoic acid and n-acetylcysteine) are currently under investigation. [ABSTRACT FROM AUTHOR]

Reduced appetite, decreased energy intake, and progressive myopathy leading to impaired functioning characterize the clinical course of chronic diseases. These symptoms are frequently observed and clinically relevant because they decrease patients' quality of life while increasing their morbidity and mortality. As the currently available therapeutic strategies are only partially effective, novel treatments are being investigated. Moderate, chronic systemic inflammation also leading to increased oxidative stress is involved in the pathogenesis of the reduction of appetite and muscle mass secondary to chronic diseases. Therefore, antiinflammatory and antioxidant agents may modulate the immune response and protect the patient against reactive oxygen species. In the past few years, experimental and clinical studies have tested the potential role of carnitine and nicotine as immunomodulating and antioxidant agents. Carnitine supplementation reduces chronic inflammation and oxidative stress in patients on hemodialysis and patients with cancer. These results are associated with reduced fatigue and improved outcome. Nicotine is more selective than acetylcholine in activating the antiinflammatory properties mediated by the vagus nerve. In animal models of sepsis and cancer, nicotine-induced activation of the nicotinic antiinflammatory pathway resulted in protection of nutritional status and improved survival. In the continuous effort to improve the metabolic alterations induced by acute and chronic diseases, the use of carnitine and nicotine may represent an interesting therapeutic approach, which needs to be supported by more clinical studies involving larger samples. [ABSTRACT FROM AUTHOR]

Background/Aims Myostatin belongs to the transforming growth factor-β superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-α may be relevant in this regard. Materials and methods Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. Results In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-α contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-α synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. Conclusions These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia. [ABSTRACT FROM AUTHOR]

Background Common variable immunodeficiency (CVI) is a primary defect of the immune system. Infections, persistent diarrhoea and malabsorption may result in malnutrition, which may in turn contribute to increased morbidity. In this paper, the prevalence of malnutrition in CVI was evaluated. Patients and methods Forty CVI patients (20 male, 20 female, aged 17–75 years) underwent anthropometric measurements from which body mass index, arm fat and muscle area were calculated. Body mass index values < 18·5 and arm fat and muscle area values < 10th percentile were considered indicative of malnutrition. Patients were divided into four groups according to circulating CD4+ T cells (lower or greater than 300 µL-1) and serum immunoglobulin A (IgA) levels (detectable and undetectable). Results Body mass index < 18·5, arm fat and muscle area < 10th percentile were observed in 23%, 58% and 44%, respectively, of patients. Lower values of body mass index, arm fat and muscle area were more frequent in patients with low CD4+ cells and undetectable IgA. Low arm fat values were more frequent in patients with diarrhoea (P = 0·03). Infectious episodes were more frequent in undetectable IgA than in detectable IgA patients (P = 0·04). Conclusions Anthropometric measurements revealed an increased rate of malnutrition in CVI patients, particularly in those with low CD4+ and undetectable IgA, suggesting that selected CVI subjects could be considered for standard or specialized nutritional support. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results. We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation. TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64·3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53·6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32·1%) at 20.00 h. Mean TNF levels were 14·3 ± 4 pg mL-1 at 08.00 h, 16·7 ± 4·6 pg mL-1 at 14.00 h (P = 0·05) and 18·5 ± 10·2 pg mL-1 at 20.00 h (P < 0·05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient = - 0·420; P = 0·026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26·3 ± 8·3, 8·9 ± 4·2, 3·8 ± 2·1, respectively; P = 0·04 at one-way anova). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant. The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss. [ABSTRACT FROM AUTHOR]

Albumin synthesis was calculated in healthy male volunteers consuming diets differing in the relative contribution of protein from animal or vegetable sources. In one study (Study 1, n = 4) two isoenergetic and isonitrogenous diets were consumed for a period of 10 d each. One diet (diet A) was animal protein rich (74%), the other one (diet V) contained 67% of vegetable protein. Albumin synthesis rate was measured from L-[(2)H(5)]phenylalanine incorporation (43 mg/kg) at the end of each dietary period. Both albumin fractional synthesis rate (FSR) (5.7 +/- 0.6 vs. 6.7 +/- 0. 8%/d, P = 0.04) and absolute synthesis rate (ASR) (123 +/- 6 vs. 143 +/- 8 mg. kg(-1). d(-1), P = 0.05) were reduced after diet V. In a second study (Study 2, n = 8) a third dietary treatment was added (Diet VS). This was similar to diet V but supplemented with soy protein (18g/d). The results of study 2 confirmed that albumin synthesis was reduced after diet V (FSR: 5.9 +/- 0.3 vs. 6.7 +/- 0. 5%/d, P = 0.015; ASR: 126 +/- 7 vs. 146 +/- 9 mg. kg(-1). d(-1), P = 0.007), but it also showed that the drop could be prevented by adding supplemental protein to the predominantly vegetarian diet (Diet VS) (FSR: 6.4 +/- 0.3%/d, P = 0.08; ASR: 140 +/- 7 mg. kg(-1). d(-1), P = 0.03). Albumin synthesis appears to be modulated by changes in the proportion of animal vs. vegetable protein occurring in the diet. The mechanism might be related to differences in digestibility and consequently in net amino acid availability between diets. [ABSTRACT FROM AUTHOR]

Eighteen untreated cancer patients and ten sex- and age-matched healthy volunteers were studied. In all patients eating behavior was investigated by means of a specific questionnaire from which the presence of anorexia and anorexia-related symptoms was assessed. To investigate the role of tryptophan in cancer anorexia, fasting plasma and CSF levels of tryptophan and other neutral amino acids were assayed in patients and controls. Cancer patients showed abnormally high plasma free tryptophan levels. In case of patients with cancer anorexia a significant rise of the ratio in plasma between free and tryptophan/large neutral amino acids, competing with tryptophan for its brain entry, was observed. This increase was correlated to a consistent rise of CSF tryptophan levels suggesting a specific role of the serotoninergic system in the pathogenesis of cancer anorexia. [ABSTRACT FROM AUTHOR]

Nineteen obese female subjects with body mass index ranging between 30 and 40 were included in a double-blind crossover study aimed at evaluating the effects of oral 5-hydroxytryptophan administration on feeding behavior, mood state and weight loss. Either 5-hydroxytryptophan (8 mg/kg/day) or placebo was administered for five weeks during which patients were not prescribed any dietary restrictions. Feeding behavior was investigated by means of a questionnaire designed to establish the onset of anorexia and related symptoms. Food intake was evaluated using a three-day diet diary. BDI, SI, STAI-T, and STAI-S were used to assess mood state. The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexiarelated symptoms, decreased food intake and weight loss during the period of observation. [ABSTRACT FROM AUTHOR]

The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article "Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?," by A. Scillitani, G. Mazziotti, C. Di Somma, S. Morertti, A. Stigliano, R. Pivonello, A. Giustina and A. Colao in the 2014 issue.