COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.

OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.

Kidney dysfunction is associated with adverse outcomes in internal medicine COVID-19 hospitalized patients.

OBJECTIVE: In this study, we aimed to evaluate the kidney involvement assessed by estimated glomerular filtration rate (eGFR), the associations with specific clinical disease variables and laboratory findings, and the predictive role of eGFR on clinical outcomes of patients admitted with COVID-19 in Internal Medicine ward in the first wave. PATIENTS AND METHODS: Clinical data of 162 consecutive patients hospitalized in the University Hospital Policlinico Umberto I in Rome, Italy, between December 2020 to May 2021 were collected and retrospectively analyzed. RESULTS: The median eGFR was significantly lower in patients with worse outcomes than in patients with favorable outcomes [56.64 ml/min/1.73 m2 (IQR 32.27-89.73) vs. 83.39 ml/min/1.73 m2 (IQR 69.59-97.08), p<0.001]. Patients with eGFR < 60 ml/min/1.73 m2 (n=38) were significantly older compared to patients with normal eGFR [82 years (IQR 74-90) vs. 61 years (IQR 53-74), p<0.001] and they had fever less frequently [39.5% vs. 64.2%, p<0.01]. Kaplan-Meier curves demonstrated that overall survival was significantly shorter in patients with eGFR < 60 ml/min/1.73 m2 (p<0.001). In multivariate analysis, only eGFR < 60 ml/min/1.73 m2 [HR=2.915 (95% CI=1.110-7.659), p<0.05] and platelet to lymphocyte ratio [HR=1.004 (95% CI=1.002-1.007), p<0.01] showed a significant predictive value for death or transfer to intensive care unit (ICU). CONCLUSIONS: Kidney involvement on admission was an independent predictor for death or transfer to ICU among hospitalized COVID-19 patients. The presence of chronic kidney disease could be regarded as a relevant factor in risk stratification for COVID-19.

Analysis of prognostic factors in COVID-19 hospitalized patients: an Italian single-center case-control study.

OBJECTIVE: COVID-19 clinical presentation ranges from asymptomatic infection to an inflammatory cytokine storm with multi-organ failure and fatal outcomes. The identification of high-risk patients for severe disease is crucial to plan an early treatment and intensive follow-up. We aimed to investigate negative prognostic factors in a group of patients hospitalized for COVID-19. PATIENTS AND METHODS: 181 patients (90 men and 91 women, mean age 66.56 ± 13.53 years) were enrolled. Each patient received a work-up including medical history, clinical examination, arterial blood gas analysis, laboratory blood tests, feasible ventilatory support required during hospital stay, intensive care setting required, duration of illness and length of hospital stay (>or<25 days). For the assessment of the severity of COVID-19, three main indicators were considered: 1) the intensive care unit (ICU) admission 2) the hospitalization length >25 days; 3) the need of non-invasive ventilation (NIV). RESULTS: The independent risk factor associated with the ICU admission were lactic dehydrogenase elevation (p=0.046), C reactive protein elevation (p=0.014) at hospital admission and direct oral anticoagulant home therapy (p=0.048); for hospital length >25 days: early corticosteroid therapy (p=0.035); for NIV treatment: ferritin elevation at hospital admission (p=0.006). CONCLUSIONS: The presence of the above factors may be useful to identify patients at high risk of developing a severe COVID-19 that need an early treatment and intensive follow-up.

Nutrition education in medical schools (NEMS) project: Promoting clinical nutrition in medical schools - Perspectives from different actors.

BACKGROUND & AIMS: Nutrition education is not adequately represented in the medical curriculum, and this prompted the European Society for Clinical Nutrition and Metabolism (ESPEN) to launch the Nutrition Education in Medical Schools (NEMS) Project in 2017. The aim of this original paper was to describe the perspectives of different actors in the promotion of nutrition education in medical schools. METHODS: On 11 November 2021, an online meeting was held on this topic, where nine representatives from different backgrounds participated in the scientific programme. More than 640 participants registered to this webinar. RESULTS: The different models of Nutrition Education in Medical Schools were introduced by Prof. Cristina Cuerda (Spain) and Prof. Maurizio Muscaritoli (Italy). The students' perspective was given by Ms. Alexandra Archodoulakis (Germany) and Ms. Sila Gürbüz (Turkey), representing the European Medical Students' Association. The dietitian's perspective was given by Dr. Kirsten Berk (The Netherlands), whereas Dr. Matti Aapro (Switzerland) gave the medical doctor (oncology)'s perspective. Ms. Clare Farrand (Australia) gave the WHO perspective and Dr. Kristiina Patja (Finland) explained the healthy lifestyle teaching to medical students. Lastly, Prof. Michael Chourdakis (Greece) and Prof. Zeljko Krznaric (Croatia) hosted the round-table discussion. CONCLUSIONS: There was strong agreement among the representatives from different settings joining this ESPEN initiative that increasing nutritional knowledge and skills of young doctors is now possible and will launch a virtuous cycle that will proactively involve all the other healthcare professionals working in the nutritional field.

A case of chronic systemic capillary leak syndrome (SCLS) exacerbated during SARS-CoV2 infection.

Systemic capillary leak syndrome (SCLS) is a very rare and lethal disease characterized by hemoconcentration and hypoalbuminemia caused by reversible plasma extravasation. The underlying cause for SCLS remains largely unknown and acute treatment has remained mainly supportive. Prophylaxis with intravenous immunoglobulin (IVIG) has been shown to successfully prevent further episodes in affected patients. We reported a case of SCLS in a patient who presented to our hospital with COVID-19 and developed profound shock.

Nutrition education in medical schools (NEMS) project: Joining ESPEN and university point of view.

BACKGROUND & AIMS: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. RESULTS: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. CONCLUSION: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).

Autonomic dysfunction in kidney diseases.

Kidney diseases are associated with many cardiovascular risk factors, such as anaemia, inflammation and chronic volume overload. Changes in the sympathovagal balance are common findings in patients with end-stage renal disease (ESRD). In particular, sympathetic hyperactivity is linked with an increase in resting heart rate leading to myocardial hypertrophy and fibrosis. The latter increases the risk of sudden cardiac death from fatal arrythmias and therefore assessment of both sympathetic and parasympathetic tones could be clinically relevant in ESRD patients. Heart rate variability and other indices are currently used to evaluate the functionality of the autonomic nervous system. Some of these have emerged as potential diagnostic tools that can support clinical decision-making processes and therapeutic strategies in patients with renal disease, including those who are on dialysis replacement therapy. In this review, we summarize the impact and the relationships between sympathovagal disturbances and kidney diseases, replacement therapies and transplantation.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

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.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

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 (non-volitional 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.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

ESPEN guidelines on nutrition in cancer patients

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet.

ESPEN guidelines on definitions and terminology of clinical nutrition.

BACKGROUND: A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. OBJECTIVE: This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. METHODS: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. RESULTS: Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. CONCLUSION: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support.

Perspectives of health care professionals on cancer cachexia: results from three global surveys.

BACKGROUND: Cachexia has a high prevalence in cancer patients and negatively impacts prognosis, quality of life (QOL), and tolerance/response to treatments. This study reports the results of three surveys designed to gain insights into cancer cachexia (CC) awareness, understanding, and treatment practices among health care professionals (HCPs). METHODS: Surveys were conducted globally among HCPs involved in CC management. Topics evaluated included definitions and synonyms of CC, diagnosis and treatment practices, and goals and desired improvements of CC treatment. RESULTS: In total, 742 HCPs from 14 different countries participated in the surveys. The majority (97%) of participants were medical oncologists or hematologists. CC was most frequently defined as weight loss (86%) and loss of appetite (46%). The terms loss of weight and decreased appetite (51% and 34%, respectively) were often provided as synonyms of CC. Almost half (46%) of the participants reported diagnosing CC and beginning treatment if a patient experienced a weight loss of 10%. However, 48% of the participants would wait until weight loss was ≥15% to diagnose CC and start treatment. HCPs also reported that 61%-77% of cancer patients do not receive any prescription medication for CC before Stage IV of disease is reached. Ability to promote weight gain was rated as the most important factor for selecting CC treatment. Key goals of treatment included ensuring that patients can cope with the cancer and treatment and have a QOL benefit. HCPs expressed desire for treatments with a more CC-specific mode of action and therapies that enhance QOL. CONCLUSIONS: These surveys underscore the need for increased awareness among HCPs of CC and its management.

Effect of personalized dietary intervention on nutritional, metabolic and vascular indices in patients with chronic kidney disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages of the disease and a high prevalence of malnutrition, inflammation, and accelerated atherosclerosis. Personalized nutritional intervention, with of a low-protein diet (LPD), since the early stages of CKD should be able to achieve significant metabolic improvements. In our study we have verified the effects of a personalized dietary intervention in patients in the CKD stages 3/4 KDOQI on nutritional, metabolic and vascular indices. PATIENTS AND METHODS: We have evaluated renal function, lipid profile, mineral metabolism, inflammatory indices, and acid-base balance of 16 patients with CKD (stages 3/4 KDOQI). Assessment of nutritional status, body composition, bone mineral density and muscle mass, using body mass index (BMI), handgrip strength, bioelectrical impedance analysis (BIA), and dual energy X-ray absorptiometry (DEXA) was performed. Vascular indices and endothelial dysfunction such as carotid intima-media thickness (cIMT) and the brachial artery flow-mediated dilation (baFMD) were also analyzed. RESULTS: After dietary interventions, we observed a significant increase in plasma bicarbonate (p = 0.004) and vitamin D levels (p = 0.03) and a concomitant significant reduction of phosphorus concentration (p = 0.001) and C-reactive protein (CRP) (p = 0.01). CONCLUSIONS: Nutritional intervention potentially plays a major role in reducing the progression of CKD and systemic complications of predialysis patients. A low-protein diet (LPD) ensuring vegetable protein intake and a reduced amount of specific micronutrients should be recommended to stage 3/4 CKD patients in order to ameliorate metabolic profile, renal outcome, and reduce cardiovascular risk factors.

Diagnostic criteria for malnutrition - An ESPEN Consensus Statement.

OBJECTIVE: To provide a consensus-based minimum set of criteria for the diagnosis of malnutrition to be applied independent of clinical setting and aetiology, and to unify international terminology. METHOD: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a group of clinical scientists to perform a modified Delphi process, encompassing e-mail communications, face-to-face meetings, in group questionnaires and ballots, as well as a ballot for the ESPEN membership. RESULT: First, ESPEN recommends that subjects at risk of malnutrition are identified by validated screening tools, and should be assessed and treated accordingly. Risk of malnutrition should have its own ICD Code. Second, a unanimous consensus was reached to advocate two options for the diagnosis of malnutrition. Option one requires body mass index (BMI, kg/m(2)) <18.5 to define malnutrition. Option two requires the combined finding of unintentional weight loss (mandatory) and at least one of either reduced BMI or a low fat free mass index (FFMI). Weight loss could be either >10% of habitual weight indefinite of time, or >5% over 3 months. Reduced BMI is <20 or <22 kg/m(2) in subjects younger and older than 70 years, respectively. Low FFMI is <15 and <17 kg/m(2) in females and males, respectively. About 12% of ESPEN members participated in a ballot; >75% agreed; i.e. indicated ≥7 on a 10-graded scale of acceptance, to this definition. CONCLUSION: In individuals identified by screening as at risk of malnutrition, the diagnosis of malnutrition should be based on either a low BMI (<18.5 kg/m(2)), or on the combined finding of weight loss together with either reduced BMI (age-specific) or a low FFMI using sex-specific cut-offs.

Updated cost-effectiveness analysis of supplemental glutamine for parenteral nutrition of intensive-care patients.

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.