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Muscle inactivity leads to muscle atrophy and insulin resistance. The branched-chain amino acid (BCAA) leucine interacts with the insulin signaling pathway to modulate glucose metabolism. We have tested the ability of a high-protein BCAA-enriched diet to prevent insulin resistance during long-term bed rest (BR). Stable isotopes were infused to determine glucose and protein kinetics in the postabsorptive state and during a hyperinsulinemic-euglycemic clamp in combination with amino acid infusion (Clamp + AA) before and at the end of 60 days of BR in two groups of healthy, young women receiving eucaloric diets containing 1 g of protein/kg per day (n = 8) or 1.45 g of protein/kg per day enriched with 0.15 g/kg per day of BCAAs (leucine/valine/isoleucine = 2/1/1) (n = 8). Body composition was determined by Dual X-ray Absorptiometry. BR decreased lean body mass by 7.6 ± 0.3 % and 7.2 ± 0.8 % in the groups receiving conventional or high protein-BCAA diets, respectively. Fat mass was unchanged in both groups. At the end of BR, percent changes of insulin-mediated glucose uptake significantly (p = 0.01) decreased in the conventional diet group from 155 ± 23 % to 84 ± 10 % while did not change significantly in the high protein-BCAA diet group from 126 ± 20 % to 141 ± 27 % (BR effect, p = 0.32; BR/diet interaction, p = 0.01; Repeated Measures ANCOVA). In contrast, there were no BR/diet interactions on proteolysis and protein synthesis Clamp + AA changes in the conventional diet and the high protein-BCAA diet groups. A high protein-BCAA enriched diet prevented inactivity-induced insulin resistance in healthy women. [ABSTRACT FROM AUTHOR]

In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020–2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report. [ABSTRACT FROM AUTHOR]

Corticosteroids lower mortality in hospitalized patients with COVID-19 pneumonia requiring oxygen support. In this observational retrospective study (September 2020–June 2021), we explored the association between receiving home corticosteroids without oxygen supply and 30-day mortality in hospitalized patients with COVID-19 pneumonia. Among a total of 794 COVID-19 pneumonia patients, 763 were included into the study (males 68%; mean age 65 ±12 years), of whom 197 (26%) received home corticosteroids (mean daily prednisone equivalent-dose 40 mg ± 12 mg; range 10–50 mg; median 50 mg; IQR 25–50 mg; for 4 days). The overall 30-day mortality of the study population was 12%. The risk of death—adjusted for age, comorbidities, administration of remdesivir and respiratory failure severity—was lower (HR 0.405; p = 0.024) in patients receiving home corticosteroids. After stratifying the study population by age categories, home corticosteroids were associated with an adjusted decrease in mortality risk in patients > 77 years (HR 0.346; p = 0.040). Home corticosteroids may lower the 30-day mortality in elderly COVID-19 patients. [ABSTRACT FROM AUTHOR]

Summary Background & aims Physical inactivity is associated with lean body mass wasting, oxidative stress and pro-inflammatory changes of cell membrane lipids. Alkalinization may potentially counteract these alterations. We evaluated the effects of potassium bicarbonate supplementation on protein kinetics, glutathione status and pro- and anti-inflammatory polyunsaturated fatty acids (PUFA) in erythrocyte membranes in humans, during experimental bed rest. Methods Healthy, young, male volunteers were investigated at the end of two 21-day bed rest periods, one with, and the other without, daily potassium bicarbonate supplementation (90 mmol × d−1), according to a cross-over design. Oxidative stress in erythrocytes was evaluated by determining the ratio between reduced (GSH) and oxidized glutathione (GSSG). Glutathione turnover and phenylalanine kinetics, a marker of whole body protein metabolism, were determined by stable isotope infusions. Erythrocyte membranes PUFA composition was analyzed by gas-chromatography. Results At the end of the two study periods, urinary pH was 10 ± 3% greater in subjects receiving potassium bicarbonate supplementation (7.23 ± 0.15 vs. 6.68 ± 0.11, p < 0.001). Alkalinization increased total glutathione concentrations by 5 ± 2% (p < 0.05) and decreased its rate of clearance by 38 ± 13% (p < 0.05), without significantly changing GSH-to-GSSG ratio. After alkalinization, net protein balance in the postabsorptive state improved significantly by 17 ± 5% (p < 0.05) as well as the sum of n-3 PUFA and the n-3-to-n-6 PUFA ratio in erythrocyte membranes (p < 0.05). Conclusions Alkalinization during long-term inactivity is associated with improved glutathione status, anti-inflammatory lipid pattern in cell membranes and reduction in protein catabolism at whole body level. This study suggests that, in clinical conditions characterized by inactivity, oxidative stress and inflammation, alkalinization could be a useful adjuvant therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess whether functional genetic polymorphisms of matrix metalloproteinases (MMPs) 1, 3, 9, and 12 are associated with arterial enlargements or aneurysms of the thoracic aorta or popliteal arteries in patients with abdominal aortic aneurysm (AAA). Methods The associations between MMP1 (−1607 G in/del, rs1799750), MMP3 (−1171 A in/del rs35068180), MMP9 (13-26 CA repeats around −90, rs2234681, rs917576, rs917577), and MMP12 (G/T missense variation, rs652438) polymorphisms and enlargements or aneurysms of the thoracic aorta and popliteal arteries were tested in 169 consecutive AAA patients. Results Thoracic aorta enlargement or aneurysm (TE/A; maximum diameter, >35 mm) was detected in 34 patients (20.1% prevalence). MMP9 rs2234681 microsatellite was the only genetic determinant of TE/A in AAA patients ( P = .003), followed by hypercholesterolemia and antiplatelet use. Carriers of both alleles with ≥22 CA repeats had a 5.9 (95% confidence interval, 1.9-18.6; P < .0001) increased odds of TE/A, and a score considering all three variables showed 98% negative predictive value and 30% positive predictive value for thoracic aortic aneurysm detection. Eighty-two popliteal artery enlargements or aneurysms (diameter >10 mm) occurred in 55 patients (33.1% prevalence). Carriers of MMP12 rs652438 C allele showed an 18% ( P = .006) increased diameter in popliteal arteries and a 2.8 (95% confidence interval, 1.3-6; P = .008) increased odds of popliteal artery enlargement or aneurysm compared with TT genotype. Conclusions Among patients with AAA, carriers of homozygous ≥22 CA repeats in MMP9 rs12234681 and of C allele in MMP12 rs652438 have a substantial risk of carrying thoracic and popliteal enlargements, respectively. [ABSTRACT FROM AUTHOR]

Summary Background & aims Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring- 2 H 5 ]phenylalanine (D 5 Phe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine. Methods We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid D 5 Phe, diluted in water, given as single oral load. The metabolic fate of D 5 Phe is either utilization for protein synthesis or irreversible hydroxylation to L[ring- 2 H 4 ]tyrosine (D 4 Tyr). AR was defined as ratio between the areas under the curves of D 4 Tyr-to-D 5 Phe plasma concentrations over 6 h meal absorption. To determine the relationships between AR and muscle changes following bed rest, quadriceps muscle volume (QMV) was determined by magnetic resonance imaging (MRI). Results At baseline, in pooled Y and O subjects, values of AR were inversely correlated with QMV (R = −0.75; p < 0.03). Following 2-weeks of inactivity, there were significant bed rest effects on AR (p < 0.01) and QMV (p < 0.03), as well as significant bed rest × group interaction for AR (p < 0.03; +9.2% in Y; +21.9% in O) and QMV (p < 0.05; −5.7% in Y; −%7.3 in O). In pooled subjects, the percentage delta changes in AR and QMV, induced by bed rest, were inversely correlated (R = −0.57; p < 0.05). Conclusion Bed rest-induced AR is much greater in the older than in younger adults. We have developed a new, simple, non-invasive method for the assessment of AR. The results indicate that this metabolic abnormality is a key mechanism for sarcopenia of aging and inactivity. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Summary Background & aims Patients with acute decompensated heart failure (ADHF) have exacerbation of symptoms and fluid retention, and high risk of re-hospitalizations and mortality. The aim of this study was to evaluate the role of phase angle at hospital admission as a prognostic marker of mortality in patients with ADHF. Methods Patients hospitalized for ADHF, with left ventricular ejection fraction (LVEF) <45% and BOSTON criteria ≥8 points were included. The patients were evaluated at hospital admission (first 36 h) and then followed up for assessment of outcomes. Phase angle was measured with tetra polar bioelectrical impedance device. Mortality data was obtained from an average of 24 months after discharge, from the medical records of the hospital and outpatient or telephone contact with patients or family members. The best-discriminatory level of phase angle was selected based on the ROC curve for mortality. Results Seventy-one patients were included and the majority was male (63%), with a mean age of 61 ± 12 years, ischemic etiology being the most prevalent (48%) and LVEF average of 26 ± 8%. Mortality was 49% at an average of 24 months after hospital discharge. The average phase angle at hospital admission was 5.6 ± 2°, and lower values were associated with higher mortality. Survivors were compared to died patients in the risk factor variables for mortality. In multivariate analysis adjusting for age, LVEF and urea, phase angle <4.8° was independently associated with increased mortality (HR 2.67; p = 0.015). Conclusions Phase angle seems to be a prognostic marker in patients with ADHF independently of other known risk factors. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to investigate the prevalence of electrolyte imbalance (EI) in the emergency department (ED) with systemic diseases in different decades of life.Methods: We enrolled patients admitted to the ED. The population study included 7941 patients, subdivided in 3 groups: young group (Y), middle-aged group (MA), and elderly group (E).Results: We observed EI in 13.7% of the whole population. Hyponatremia (hNa+) is the most frequent EI (44%) followed by hypokalemia (hK+) (39%), hyperkalemia (HK+) (13%), and hypernatremia (HNa+) (4.4%). In the Y group, the EI occurred in 7.1% of all patients (P< .05 vs MA and E), whereas in the MA group, they were shown in 11.5% of patients and in the E group in 22% of all patients group (P< .05 vs MA and Y). In the Y group, gastrointestinal diseases are the most frequently associated disease (24.6%; P< .05 vs MA and E). In the MA group, the most frequently associated disease was a current cardiovascular disease (29.7%; P< .05 vs Y and E). In the E group, the frequently associated diseases are cardiovascular (22.8%; P< .05 vs Y) and lung diseases (16.7%; P< .05 vs MA and Y).Conclusions: In our study, 13.7% of all patients showed an EI, and only 2% of cases were alone without any associated systemic disease. Most EIs are associated to other systemic diseases. The present data also depict different age-related and disease-associated prevalence patterns of EI, thus highlighting a complex clinical scenario. [ABSTRACT FROM AUTHOR]

Summary Background The correlation between Parkinson disease and malnutrition is well established, however a protein-restricted diet is usually prescribed because of potentially negative interactions between dietary amino acids and l -dopa pharmacokinetics. This strategy could increase the risk of further nutritional deficits. Methods A monocentric, prospective, randomized, double-blind pilot study was performed on two groups of Parkinson-affected, protein-restricted, patients: Intervention (n = 7; amino acid supplementation twice daily) and Placebo (n = 7; placebo supplementation twice daily). At enrolment, after 3- and 6-month supplementation, neurological evaluations (UPDRS III, Hoenh–Yahr scale, l -dopa equivalent dose assessment) were performed and blood sample was collected to define insulin sensitivity (QUICKI index) and oxidative stress (oxidized and reduced glutathione). Repeated measure ANCOVA was applied to define time effect and time × treatment interaction. Results Participants were comparable at baseline for all assessed parameters. Neurological outcomes and l -dopa requirement were comparable in both group after 6-month of supplementation, without time × treatment interaction. The decrease in insulin sensitivity, as assessed by QUICKI index, observed after 6 months in both groups, was greater in Placebo than in Intervention (time effect p < 0.001; time × treatment interaction p = 0.01). Moreover, despite no changes in total erythrocyte glutathione concentrations, oxidized glutathione levels decreased by 28 ± 17% in the Intervention while increased by 55 ± 38% in Placebo (time effect p = 0.05; time × treatment interaction p = 0.05), after 6-month supplementation. Conclusions Amino acid supplementation, assumed with shrewd temporal distribution, did not show detrimental effects on neurological and pharmacological control in protein-restricted Parkinson-affected patients, chronically treated with l -dopa. Furthermore, daily amino acid supplementation partially counteracted insulin resistance development and the loss in antioxidant availability. [ABSTRACT FROM AUTHOR]

Background & aims: Sarcopenic obesity may be defined by a high fat to fat-free mass (FM/FFM) ratio. Skeletal muscle may be negatively influenced by th e pro-inflammatory milieu associated with visceral fat, while the loading effect induced by a heavier body mass index (BMi) may enhance muscle anabolism. Recently, a new anthropometric measure based on waist circumference (A Body Shape Index, ABSI) was developed. In this study we have assessed the predictive power of ABSI on the FFM index (FFMI), a surrogate marker of lean mass. Methods: Standard anthropometric parameters and ABSI as well as body composition data (fat and fat-free mass determined by bioelectrical impedance analysis) were assessed in 111 female and 89 male overweight/obese subjects, with no clinically significant co-morbidities. Groups with higher- or lower-ABSI were identified according to median values of this index. Results: In women and men, ABSI did not correlate with BMI, while multiple linear regression indicated that BMI ((β-coefficients: 0.62 and 0.77, respectively) and ABSI (β-coefficients: -0.26 and -0.22, respectively) independently predicted FFMI (multiple R: 0.72 and 0.83, respectively, P < 0.001). Men and women with lower-ABSI exhibited significantly greater FFMI than the higher-ABSI groups for comparable values of BMI. In men, ABSI was correlated positively with C-reactive protein (CRP) (R = 0.30; P < 0.05) and negatively with th e reciprocal of insulin (R = 0.28; P < 0.05), an index of insulin sensitivity. FM/FFM ratio significantly (P < 0.01) correlated with CRP (R = 0.31) in women only. Conclusions: ABSI, a recently introduced marker of abdominal adiposity, may contribute to define the risk of sarcopenia in overweight/obese individuals. [ABSTRACT FROM AUTHOR]

Background & aims: Sarcopenic obesity may be defined by a high fat to fat-free mass (FM/FFM) ratio. Skeletal muscle may be negatively influenced by th e pro-inflammatory milieu associated with visceral fat, while the loading effect induced by a heavier body mass index (BMi) may enhance muscle anabolism. Recently, a new anthropometric measure based on waist circumference (A Body Shape Index, ABSI) was developed. In this study we have assessed the predictive power of ABSI on the FFM index (FFMI), a surrogate marker of lean mass. Methods: Standard anthropometric parameters and ABSI as well as body composition data (fat and fat-free mass determined by bioelectrical impedance analysis) were assessed in 111 female and 89 male overweight/obese subjects, with no clinically significant co-morbidities. Groups with higher- or lower-ABSI were identified according to median values of this index. Results: In women and men, ABSI did not correlate with BMI, while multiple linear regression indicated that BMI ((β-coefficients: 0.62 and 0.77, respectively) and ABSI (β-coefficients: -0.26 and -0.22, respectively) independently predicted FFMI (multiple R: 0.72 and 0.83, respectively, P < 0.001). Men and women with lower-ABSI exhibited significantly greater FFMI than the higher-ABSI groups for comparable values of BMI. In men, ABSI was correlated positively with C-reactive protein (CRP) (R = 0.30; P < 0.05) and negatively with th e reciprocal of insulin (R = 0.28; P < 0.05), an index of insulin sensitivity. FM/FFM ratio significantly (P < 0.01) correlated with CRP (R = 0.31) in women only. Conclusions: ABSI, a recently introduced marker of abdominal adiposity, may contribute to define the risk of sarcopenia in overweight/obese individuals. [ABSTRACT FROM AUTHOR]

Summary The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0–1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2–1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible. [ABSTRACT FROM AUTHOR]

Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Since the publications of the ESPEN guidelines on enteral and parenteral nutrition in ICU, numerous studies have added information to assist the nutritional management of critically ill patients regarding the recognition of the right population to feed, the energy-protein targeting, the route and the timing to start. Methods: We reviewed and discussed the literature related to nutrition in the ICU from 2006 until October 2013. Results: To identify safe, minimal and maximal amounts for the different nutrients and at the different stages of the acute illness is necessary. These amounts might be specific for different phases in the time course of the patient's illness. The best approach is to target the energy goal defined by indirect calorimetry. High protein intake (1.5 g/kg/d) is recommended during the early phase of the ICU stay, regardless of the simultaneous calorie intake. This recommendation can reduce catabolism. Later on, high protein intake remains recommended, likely combined with a sufficient amount of energy to avoid proteolysis. Conclusions: Pragmatic recommendations are proposed to practically optimize nutritional therapy based on recent publications. However, on some issues, there is insufficient evidence to make expert recommendations. [Copyright &y& Elsevier]

The article focuses on Congress codifying several disciplinary procedural rights for service members in the Uniform Code of Military Justice (UCMJ). It mentions the military right against self-incrimination and compares to the protection against the civilian equivalent along with immunity for both laws including military, and civilian. It further mentions that the judiciary developments would enable the immunized testimony for service member in nonjudicial proceedings.

Summary: Background & aims: Although decreased levels of circulating TRAIL have been associated to cardiovascular risk and overall mortality, the mechanisms controlling TRAIL levels in physiopathological conditions are currently unknown. The aim of the present study was to investigate whether changes in the energy intake and insulin sensitivity may influence circulating TRAIL, and to analyze potential relationships between circulating TRAIL and changes in fat mass in healthy subjects receiving hypocaloric or hypercaloric diets. Methods: Three distinct groups of participants were studied, at the end of a 14-day (n = 9), 35-day (n = 30) or 60-day (n = 16) period of experimental bed rest to induce insulin resistance and during controlled ambulation, after receiving eucaloric, hypocaloric or hypercaloric diets. Results: After bed rest conditions, energy restriction significantly decreased circulating TRAIL, while overfeeding significantly increased TRAIL levels with respect to eucaloric control subjects. Moreover, a positive correlation was found between levels of circulating TRAIL and energy intake as well as between circulating TRAIL and energy balance, as determined by changes in fat mass in these subjects. Conclusions: Circulating levels of TRAIL exhibit a clear-cut positive correlation with the energy intake and balance in healthy subjects during experimental physical inactivity. [Copyright &y& Elsevier]

Abstract: Background: Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery. Methods and Results: We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 wk) and late (> 6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients. Conclusions: ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF. [Copyright &y& Elsevier]

Abstract: Background: The role of matrix metalloproteinases (MMPs) polymorphisms on heart failure (HF) susceptibility, phenotypic characteristics, and prognosis has been poorly explored. Methods and Results: We studied 313 HF patients with left ventricular systolic dysfunction and 367 healthy control subjects. Genotyping of MMP-1 (−1607 1G/2G), MMP-3 (−1171 5A/6A), and MMP-9 (−1562 C/T) polymorphisms was performed by polymerase chain reaction. Allelic and genotypic frequencies of MMP-1, -3, and -9 were similar in HF patients and controls. MMP1 2G allele carriers were positively associated to ischemic etiology and history of myocardial infarction (all P values <.05). Patients were followed-up for a median of 40 months and 58 HF-related deaths occurred during this period. HF-related survival was significantly better in MMP1 2G allele carriers (71% versus 42% for 1G/1G patients, P = .002) and in MMP-3 6A allele carriers (70% versus 61% for 5A/5A patients, P = .064), particularly in non-ischemic patients (P = .039). MMP1 2G allele was independently associated to HF survival after adjustment for several other predictors of risk (hazard ratio 0.47, 95% confidence interval 0.27 to 0.82; P = .008). Conclusions: MMP-1, -3, and -9 polymorphisms were not associated to HF susceptibility. However, MMP1 2G allele carriers were related to a higher prevalence of ischemic etiology among patients with systolic HF and better HF-related prognosis. [Copyright &y& Elsevier]

Summary: Background & aims: Low-grade systemic inflammation and pro-inflammatory pattern of cell membrane fatty acid composition characterize patients affected by type 2 diabetes and metabolic syndrome. We hypothesize that inactivity-induced insulin resistance could affect levels of pro-inflammatory fatty acids in cell membranes. Methods: Thirty healthy, male, young volunteers were investigated before and after 35-day experimental bed rest. Diet composition was adapted to previous dietary habits. Fatty acid composition of erythrocyte membranes was analyzed by gas-chromatography using flame ionization detector. Results: Following bed rest, the HOMA index of insulin resistance significantly increased by +51±11% (P <0.01). Bed rest was associated with increased n-6 polyunsaturated (+4.7±2.2%; P <0.01) and decreased monounsaturated (−4.8±1.5%; P <0.01) fatty acid content in erythrocyte membranes. Fractional content of arachidonic acid increased by +14±12% (P =0.01) following inactivity. Δ5 and Δ9 desaturase indexes, as estimated from product-to-precursor ratios, significantly diminished following bed rest from 9.6±0.4 to 8.4±0.3 (P <0.001) and from 0.72±0.02 to 0.69±0.01 (P <0.05), respectively. The n-3 fatty acids, α-linolenic and eicosapentaenoic, were decreased (P =0.05) following inactivity by 4.7±13.2% and 3.8±5.2%, respectively. Conclusions: Inactivity-mediated insulin resistance was associated with altered Δ5 and Δ9 desaturase indexes and with pro-inflammatory fatty acid pattern in erythrocyte membranes. These abnormalities could contribute to the low-grade inflammation associated to inactivity. [Copyright &y& Elsevier]

Summary: Chronic diseases as well as aging are frequently associated with deterioration of nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired quality of life and increased risk for morbidity and mortality. Although simple and effective tools for the accurate screening, diagnosis and treatment of malnutrition have been developed during the recent years, its prevalence still remains disappointingly high and its impact on morbidity, mortality and quality of life clinically significant. Based on these premises, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN with the aim of developing and spreading the knowledge on the basic and clinical aspects of cachexia and anorexia as well as of increasing the awareness of cachexia among health professionals and care givers. The definition, the assessment and the staging of cachexia, were identified as a priority by the SIG. This consensus paper reports the definition of cachexia, pre-cachexia and sarcopenia as well as the criteria for the differentiation between cachexia and other conditions associated with sarcopenia, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics. [Copyright &y& Elsevier]

Chronic diseases as well as aging are frequently associated with deterioration of nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired quality of life and increased risk for morbidity and mortality. Although simple and effective tools for the accurate screening, diagnosis and treatment of malnutrition have been developed during the recent years, its prevalence still remains disappointingly high and its impact on morbidity, mortality and quality of life clinically significant. Based on these premises, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN with the aim of developing and spreading the knowledge on the basic and clinical aspects of cachexia and anorexia as well as of increasing the awareness of cachexia among health professionals and care givers. The definition, the assessment and the staging of cachexia, were identified as a priority by the SIG. This consensus paper reports the definition of cachexia, pre-cachexia and sarcopenia as well as the criteria for the differentiation between cachexia and other conditions associated with sarcopenia, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics. [ABSTRACT FROM AUTHOR]

The article presents a study on hydrogen peroxide (H2O2)-dependent and -independent myocardial remodeling which demonstrates the nature of cardiomyopathy and heart failure in transgenic mice. It explores the methods used in the study including the use of Gαq-overexpressing mice and production of crossbreeds that show catalase overexpression. Moreover, it concludes that catalase overexpression prevented myocyte apoptosis, myocyte hypertrophy, and heart failure.

The article focuses on a study which tested the hypothesis that episodes of acute chronic heart failure (AHFS) were associated with increased levels of troponin and extracellular matrix markers. The study discovered that troponin I and three markers of extracellular matrix (ECM) turnover were elevated. It concluded that AHFS episodes were associated with transient increases in markers of myocyte injury and ECM turnover.

Abstract: A hundred years from its description, Chagas cardiomyopathy remains a challenging disease. Although successful vector-control strategies have decreased the incidence of Chagas disease in several Latin American countries, both migration to urban areas and immigration have spread the disease worldwide; and now, blood transfusion, organ transplantation, and vertical transmission are a concern. The pathogenesis of Chagas cardiomyopathy involves complex host-parasite interactions, where low-grade but incessant systemic infection and triggered autoimmune reaction are the main mechanisms for its development, with the contribution of autonomic damage and microvascular disturbances. Chagas cardiomyopathy is the most important clinical presentation of Chagas disease and comprises a wide range of manifestations, including heart failure, arrhythmias, heart blocks, sudden death, thromboembolism, and stroke. Recently, simple clinical prognostic scores have been developed to identify high-risk patients and help with management. The treatment of Chagas cardiomyopathy focuses mostly on managing heart failure, arrhythmias, and thromboembolism. The role of specific antiparasitic therapy in the chronic form is not yet defined, and a randomized trial is now under way to address this crucial point. In this article, we review the main clinical aspects of Chagas cardiomyopathy and underscore some upcoming challenges for the appropriate control, diagnosis, and management of this complex disease. [Copyright &y& Elsevier]

Summary: Nutritional support in the intensive care setting represents a challenge but it is fortunate that its delivery and monitoring can be followed closely. Enteral feeding guidelines have shown the evidence in favor of early delivery and the efficacy of use of the gastrointestinal tract. Parenteral nutrition (PN) represents an alternative or additional approach when other routes are not succeeding (not necessarily having failed completely) or when it is not possible or would be unsafe to use other routes. The main goal of PN is to deliver a nutrient mixture closely related to requirements safely and to avoid complications. This nutritional approach has been a subject of debate over the past decades. PN carries the considerable risk of overfeeding which can be as deleterious as underfeeding. Therefore the authors will present not only the evidence available regarding the indications for PN, its implementation, the energy required, its possible complementary use with enteral nutrition, but also the relative importance of the macro- and micronutrients in the formula proposed for the critically ill patient. Data on long-term survival (expressed as 6 month survival) will also be considered a relevant outcome measure. Since there is a wide range of interpretations regarding the content of PN and great diversity in its practice, our guidance will necessarily reflect these different views. The papers available are very heterogeneous in quality and methodology (amount of calories, nutrients, proportion of nutrients, patients, etc.) and the different meta-analyses have not always taken this into account. Use of exclusive PN or complementary PN can lead to confusion, calorie targets are rarely achieved, and different nutrients continue to be used in different proportions. The present guidelines are the result of the analysis of the available literature, and acknowledging these limitations, our recommendations are intentionally largely expressed as expert opinions. [Copyright &y& Elsevier]

Summary: Background & aims: Insulin resistance is common in maintenance hemodialysis (MHD) and it can contribute to exceedingly high mortality in MHD patients. Ghrelin is a gastric hormone whose total plasma concentration is increased in MHD. Emerging data suggest a potential role of ghrelin to modulate intermediate metabolism but the metabolic impact of ghrelin in chronic kidney disease is unknown. The current study aimed at assessing the potential relationships between ghrelin and insulin sensitivity in MHD. Methods: Total (T-Ghr) and acylated (A-Ghr) ghrelin as well as insulin-mediated glucose disposal [(M): hyperinsulinemic–euglycemic clamp] were measured in non-diabetic non-obese ambulatory MHD patients (n=19, 16Males). C-reactive protein (CRP) was also measured since systemic inflammation is associated with insulin resistance in non-renal patients and inflammation is negatively modulated by ghrelin in experimental models. Results: Compared to control subjects (C: n=9, 7Males), MHD had similar body fat and resting energy expenditure but reduced M and increased CRP (P<0.05). MHD also had higher T-(P<0.05) but not A-Ghr. M was associated positively with T-Ghr and negatively with CRP in linear regression analysis in MHD. In stepwise multiple regression analysis only T-Ghr remained associated with M (P<0.05) in a model including A-Ghr and CRP. Conclusions: Insulin sensitivity is associated negatively with systemic inflammation and positively with total plasma ghrelin in non-diabetic MHD patients. Based on available knowledge these results suggest a potential novel role of ghrelin in preserving insulin sensitivity in MHD. [Copyright &y& Elsevier]

Abstract: The eukaryotic elongation factors (eEF1A2 and eEF1A1) play a key role in translation of messenger RNA (mRNA) to protein. In skeletal muscle of healthy humans, EEF1A2 is overexpressed and selected over EEF1A1. In cellular stress models, muscle EEF1A1 expression increased and was associated with apoptosis and catabolism. We have determined mRNA levels of EEF1A1 and EEF1A2, as well as those of other proapoptotic genes, such as p66(ShcA) and c-MYC, in skeletal muscle of severely traumatized patients and healthy volunteers. Muscle protein kinetic was determined by stable isotopes and the arteriovenous technique. The patients were in a hypercatabolic condition because the rate of muscle proteolysis exceeded that of synthesis. Mean mRNA levels of EEF1A1 and EEF1A2 were 165- and 29-fold greater (P < .01) in patients than in the control group, respectively. Mean p66(ShcA) mRNA levels were 3-fold greater (P < .05) in patients than in the controls. In contrast, c-MYC mRNA levels were not significantly different in patients and healthy controls. In patients, muscle mRNA levels of EEF1A1 and p66(ShcA) directly correlated (P < .05) with the rate of proteolysis (R = 0.901 and R = 0.826, respectively). This is in agreement with a reduction in actin and tubulin protein content, both markers of cytoskeletal and sarcomeric disorganization, and with an increased poly(adenosine diphosphate–ribose) polymerase cleavage, a marker of apoptosis. In conclusion, in hypercatabolic traumatized patients, an up-regulation of muscle EEF1A1 and p66(ShcA) relates to proteolysis rate, suggesting an involvement of these genes in muscle catabolic response. [Copyright &y& Elsevier]

Summary: Background & aims: Two different ways of thinking pervaded the history of science: rationalism and empiricism. In theory, these two paradigms are not necessarily in conflict. In practice, there has always been tension between them. The coming of evidence-based medicine put empiricism in a privileged position, but empiricism without a rationalistic guide could even be usefulness. The aim of this work is to present the tension between the rational reasons to administer immunonutrients to patients with sepsis and the controversial empirical evidence stemming from clinical trials. Methods: We reviewed the literature on immunonutrition in sepsis from the rationalist and the empiricist perspectives. Results: The large body of evidence for positive effects of immunonutrients in experimental models and the contradictory results from clinical trials make the discussion on immunonutrition in sepsis a typical example where the conflict between rationalism and empiricism hampered the advancement of knowledge and the implementation of new effective therapies into clinical practice. Conclusions: Future research projects involving immunonutrients should be based on robust knowledge of basic mechanisms of action to be properly addressed in clinical trials. [Copyright &y& Elsevier]

Abstract: Background: Scarce data are available to predict in-hospital mortality for decompensated heart failure (HF) in South American populations. Methods and Results: We evaluated 779 consecutive HF admissions defined by the Boston criteria in a tertiary care hospital. Stepwise logistic regression was used to determine independent correlates of in-hospital mortality, derived from 83 potential predictors collected on hospital admission. A clinical score rule (HF Revised Score) was created using the regression coefficient estimates derived from multivariate modeling. During hospital stay, 77 (10%) deaths occurred and 6 clinical characteristics were independently associated with in-hospital mortality: presence of cancer (P < .001), systolic blood pressure ≤124 mm Hg (P < .001), serum creatinine >1.4 mg/dL (P = .02), blood urea nitrogen >37 mg/dL (P = .03), serum sodium <136 mEq/L (P = .03), and age >70 years old (P = .03). Both the Acute Decompensated Heart Failure National Registry stratification algorithm and the proposed HF Revised Score performed adequately to predict in-hospital mortality (“c” statistics = 0.71 and 0.76, respectively). The newly proposed score, however, discriminated a very low-risk group (101 [13%]) in whom all patients were discharged home, representing patients admitted with none of the 6 predictors of risk. Conclusion: HF risk stratification can be accurately accomplished during the first day of admission with simple and easily obtained clinical variables. [Copyright &y& Elsevier]