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Background and Aims: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults., Methods: Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP)., Results: Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS., Conclusion: Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP., Competing Interests: Conflict of interest All authors report no potential conflicts of interest in relation to this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Parenteral nutrition (PN) can supply all essential nutrients to a patient with gastrointestinal insufficiency. However, the sensitivity to lipid peroxidation might increase in those receiving PN, especially home parenteral nutrition (HPN). This study aimed to investigate whether PN affects the antioxidant balance of plasma of HPN patients without comorbidities and whether this balance is influenced by comorbidities and according to the type of lipid emulsion included in the PN., Methods: Adult patients on HPN (n = 86) received one of three types of lipid emulsion (based on 1) soyabean oil, 2) olive and soyabean oil or 3) soyabean, coconut, olive and fish oil) in all-in-one mixtures; in addition healthy controls (n = 66) were studied as comparators. HPN patients were classified to the following subgroups: 1) patients without (n = 58) or with (n = 28) comorbidities 2) patients on Intralipid (G INTRA , n = 53), ClinOleic (G CLIN , n = 17) or SMOFlipid (G SMOF n = 16). The activities of total glutathione peroxidase (GSH-Px), selenium dependent glutathione peroxidase (Se-GSHPx) and glutathione S-transferase (GST) in plasma were determined spectrophotometrically. The antioxidant potential of plasma was determined using oxygen radical absorbance capacity (ORAC). The lipid peroxidation marker malondialdehyde (MDA) was analyzed with high performance liquid chromatography., Results: MDA concentration was the highest in G INTRA and the lowest in G SMOF (p < 0.05). G SMOF also had the highest activity of GSH-Px. No differences in Se-GSHPx, GST and ORAC were observed among G INTRA , G CLIN and G SMOF . Comparing with healthy controls, significantly lower GST (p = 0.0293) and ORAC (p < 0.0001) were observed in the HPN patients. Among all measured parameters only the concentration of MDA was significantly higher in patients with comorbidities compared to those without them. Comorbidities did not influence MDA level in G INTRA and G SMOF being still the lowest in G SMOF (p = 0.0033). In contrast, significantly higher MDA level was observed for G CLIN in those with vs. without comorbidities (p = 0.0262)., Conclusions: Patients on HPN have lower antioxidant defenses than healthy controls. The type of lipid emulsion used in HPN affects lipid peroxidation (even after taking into account comorbidities which often involve oxidative stress) being the highest in G INTRA and the lowest in G SMOF . Thus, to minimize the risk of oxidative stress, SMOFlipid can be considered in patients in HPN especially for those with comorbidities. ClinOleic can be considered in HPN patients without comorbidities. The observation should be confirmed in larger studies., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Research reporting plasma micronutrient status and its impact on clinical outcomes in paediatric cancer is scarce. Therefore, we investigated the prevalence of plasma micronutrient abnormalities and their impact on clinical outcomes and treatment complications., Methods: A multicentre prospective-cohort study of children aged <18 years diagnosed with cancer was performed between Aug 2010-Jan 2014. Clinical and nutritional data were collected at diagnosis, 3, 6, 9, 12 and 18 months. Micronutrient status was established using in-house laboratory references (vitamin B12, vitamin A and Vitamin E/Ch) and aged adjusted Z-scores (Mg, Se, Zn and Cu) generated from a cohort of healthy Scottish children. Clinical outcomes were classified as "event free survival (EFS)" or "event" (relapse, death, new metastasis or becoming palliative) and treatment complications. Descriptive statistics, logistic regression and multilevel analysis were performed., Results: Eighty-two patients [median (IQR) 3.9 (1.9-8.8) years, 56% males] were recruited. Of these, 72 (88%) samples were available, 74% (53/72) patients had micronutrient abnormalities at baseline; deficiencies (25%, 18/72), excesses (19%, 14/72) and a combination of both (29%, 21/72), which continued for 18 months. Vitamin A deficiency (15%, 3/20) and excess (50%, 10/20) were most prevalent at 18 months, whilst vitamin E/Cholesterol and vitamin B12 were mostly within the normal range. Prevalence of Zn deficiency at diagnosis was 36% (16/44 adjusted for CRP), which remained at these levels throughout the study. Reduction in each selenium concentration unit increased the odds of an event by 2% (OR 0.02) and lower Se predicted higher complications at diagnosis [β (-1.2); t (-2.1); 95% CI (-2.9 - (-0.04)); p = 0.04], 3 months [β (-3.9); t (-4.2); 95% CI (-5.57 - (-2.02)); p < 0.001] and 12 months [β (-2.3); t (-2.4); 95% CI (-4.10 - (-0.34)); p = 0.02]., Conclusions: Given the prevalence of micronutrient abnormalities and the negative impact of low selenium on clinical outcome, micronutrient status should be assessed and monitored in paediatric cancer patients. Larger multicentre population based studies and clinical trials are now warranted., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Myosteatosis is gathering attention as a feasible indicator for sarcopenia and increased risk of morbidity. However, the prognostic value of intramuscular adipose tissue content (IMAC) as an assessment method for myosteatosis remains controversial. The objectives of this study are to compare the prognostic value of intramuscular adipose tissue content (IMAC) with our newly-developed modified IMAC (mIMAC), and to assess the clinical significance of mIMAC in colorectal cancer (CRC) and gastric cancer (GC)., Methods: We evaluated 892 patients with CRC or GC, and assessed preoperative IMAC and mIMAC to compare their prognostic and predictive values for postoperative infectious complications in both cohorts., Results: Both preoperative IMAC and mIMAC were sex- and disease-dependent, and positively or negatively correlated with age in CRC and GC patients (IMAC: CRC: r = 0.33, P < 0.0001; GC: r = 0.304, P < 0.0001; mIMAC: CRC: r = -0.364, P < 0.0001; GC: r = -0.263, P < 0.0001). In contrast to IMAC, lower preoperative mIMAC was significantly associated with disease-development factors, and was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS) in both CRC (OS: hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.25-3.03, p = 0.003; DFS: HR: 1.93, 95% CI: 1.22-3.04, p = 0.005) and GC patients (OS: HR: 2.11, 95% CI: 1.22-3.68, P = 0.008; DFS: HR: 2.03, 95% CI: 1.18-3.5, P = 0.011). Patients with postoperative remote infections had a poorer prognosis compared with those without in both cohorts (CRC: HR: 2.67, 95% CI: 1.46-4.89, P = 0.002; GC: HR: 3.01, 95% CI: 1.47-6.19, P = 0.003), and low mIMAC was an independent risk factor for postoperative remote infection in both cancers (CRC: odds ratio (OR): 2.56, 95% CI: 1.06-6.23, P = 0.038; GC: OR: 2.8, 95% CI: 1.03-7.58, P = 0.043). Finally, we assessed the correlation between IMAC or mIMAC and the representative frailty markers body mass index (BMI), serum albumin, and prognostic nutritional index (PNI). We found a positive correlation between preoperative mIMAC and all of these markers in both cohorts (CRC: BMI: r = 0.193, P < 0.0001; serum albumin: r = 0.42, P < 0.0001; PNI: r = 0.39, P < 0.0001; GC: BMI: r = 0.22, P < 0.0001; serum albumin: r = 0.212, P < 0.0001; PNI: r = 0.287, P < 0.0001)., Conclusions: Preoperative mIMAC could be useful for perioperative and postoperative management in CRC and GC., Competing Interests: Conflict of interest All authors have no conflicts of interest to disclose for this study., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: Patients with gastric adenocarcinoma (GA) often develop malnutrition, which deteriorates after cancer surgery and negatively affects surgical outcomes. Despite being an abundant and versatile amino acid involved in the immune system and metabolic functions, glutamine levels are significantly depleted among patients who are critically ill or hypercatabolic. Therefore, this study aimed to investigate whether parenteral glutamine supplementation may improve nutritional status and surgical outcomes., Methods: This retrospective, single-center cohort study included patients with GA who underwent gastrectomy between January 2007 and June 2019. Patients were classified into either the non-glutamine or glutamine group. Propensity score matching was used to minimize the bias in patient demographics. Furthermore, the average parenteral glutamine dose from the day of surgery to postoperative day four was calculated in g/kg/day. Surgical outcomes (length of hospitalization, major complication, and mortality) and changes in lymphocyte count and serum albumin levels 7 days post-surgery were assessed in both matched groups using adjusted models., Results: A total of 1950 patients were reviewed, among whom 522 (26.8%) received parenteral glutamine supplementation (glutamine dose ranging from 0.05 to 0.49 g/kg/day). Among the included patients, 57.2% were males, and the median age was 64.9 years. After matching, there were 478 cases in each group. No differences in surgical outcomes and changes in lymphocyte count were observed between both matched groups. The glutamine group exhibited a smaller decrease in serum albumin levels compared to the non-glutamine group (-0.6 vs. -1.1 g/dL; P < 0.001). The adjusted matched model showed that glutamine dose contributed significantly toward increasing serum albumin levels (coefficient = 0.08 per 0.1 g/day/kg increment in glutamine; 95% confidence interval: 0.04 to 0.10; P < 0.001)., Conclusions: Perioperative parenteral glutamine supplementation had a positive dose-dependent impact on the recovery of serum albumin levels among patients with GA undergoing gastrectomy, implying that glutamine supplementation improved postoperative nutritional suppression and ameliorated stress-associated inflammation. Although glutamine supplementation was not associated with surgical outcomes, further studies should be conducted to evaluate the clinical significance of serum albumin restoration., Competing Interests: Conflict of interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: This position paper summarizes theoretical and practical aspects of the monitoring of artificial nutrition and metabolism in critically ill patients, thereby completing ESPEN guidelines on intensive care unit (ICU) nutrition., Methods: Available literature and personal clinical experience on monitoring of nutrition and metabolism was systematically reviewed by the ESPEN group for ICU nutrition guidelines., Results: We did not identify any studies comparing outcomes with monitoring versus not monitoring nutrition therapy. The potential for abnormal values to be associated with harm was clearly recognized. The necessity to create locally adapted standard operating procedures (SOPs) for follow up of enteral and parenteral nutrition is emphasised. Clinical observations, laboratory parameters (including blood glucose, electrolytes, triglycerides, liver tests), and monitoring of energy expenditure and body composition are addressed, focusing on prevention, and early detection of nutrition-related complications., Conclusion: Understanding and defining risks and developing local SOPs are critical to reduce specific risks., (Copyright © 2018. Published by Elsevier Ltd.)

Background & Aims: The geriatric nutritional risk index (GNRI) is a simple but useful nutritional marker for all-cause mortality and cardiovascular mortality in patients undergoing hemodialysis (HD). However, whether the GNRI can predict infection-related mortality in patients undergoing HD remains unclear, and there is insufficient evidence regarding whether the GNRI improves the predictive value for risk assessment beyond the existing conventional nutritional markers. Here, we investigated the association between the GNRI and infection-related mortality in patients undergoing HD and evaluated the predictive value of GNRI., Methods: A prospective cohort study was performed on a total of 3436 Japanese HD patients aged ≥18 years. Patients were divided into four groups by quartiles of GNRI: (Quartile 1 [Q1], >100.2; Q2, 95.9-100.2; Q3, 90.8-95.8; Q4, <90.8). We estimated the relationship between GNRI and all-cause mortality and infection-related mortality using a Cox proportional hazards model. To assess the additional predictive value of the GNRI in risk assessment, we compared the c-statistic, net reclassification improvement, and integrated discrimination improvement among serum albumin, serum creatinine, and the GNRI., Results: During follow-up period (median, 4.0 years), a total of 564 patients died; 120 of these patients died of infectious disease. All-cause mortality and infection-related mortality increased linearly with lower GNRI levels. After adjusting for confounding risk factors, the GNRI was an independent predictor of infection-related mortality as well as all-cause mortality (hazard ratio [HR], 5.89; 95% confidence interval [CI], 2.85-13.8; P < 0.001 for Q4 vs. Q1, HR, 2.62; 95% CI, 1.23-6.24; P = 0.01 for Q3 vs. Q1). Additionally, when the GNRI was incorporated into a model with potential risk factors instead of serum albumin, the c-statistic increased significantly (0.811 vs. 0.821, P = 0.03), and the net reclassification improvement and integrated discrimination improvement was 0.26 (P = 0.005) and 0.005 (P = 0.01). This association was more apparent in the older patients (0.739 vs. 0.760, P = 0.02) than in the younger patients (0.916 vs. 0.912, P = 0.35). Similar results were observed between serum creatinine and the GNRI, but the difference did not reach statistical significance., Conclusions: Lower GNRI levels are an independent risk factor for infection-related mortality in patients undergoing HD. Moreover, addition of the GNRI to models with standard risk factors significantly improves the predictive ability of infection-related mortality, especially in older patients., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Malnutrition-inflammation complex syndrome (MICS), hyperhomocysteinemia, calcium and phosphate levels derangement have been predicted as important contributing factors for the progression of cardiovascular burden. Among patients with earlier stage of CKD, hypoalbuminaemia and inflammation deliberated as non-traditional cardiovascular risk factors, which add more burden to circulatory disease, mortality and rapid advancement to CKD stage 5., Aim: The aim of the study is to evaluate inflammation and nutritional status of CKD patients not on dialysis using Malnutrition inflammation score (MIS) and to verify the association with mortality in the follow-up period., Methods and Material: In this prospective cohort study 129 (66 males, 63 females) pre-dialysis CKD patients enrolled between June 2013 to August 2014 and censored until March 2017. Malnutrition and Inflammation assessed using Malnutrition inflammation score. Blood urea nitrogen, serum creatinine, albumin, Interleukin - 6, highly sensitive C reactive protein (hsCRP), total cholesterol and anthropometric data were analyzed., Results: The Malnutrition inflammation score in pre-dialysis CKD patients ranged from 0 to 18 with the median score of two. During 36 or more months of follow-up, there were 30 (23.2%) deaths, 35 (27%) patients initiated on hemodialysis, one (0.7%) patient was initiated on peritoneal dialysis, two (1.4%) patients underwent renal transplantation and two (1.4%) patients were lost for follow-up. In this study, 33% had varying degree of malnutrition and inflammation. Patients who had MIS ≥7 had significant increase in IL-6 (p = 0.003) and HsCRP levels (p < 0.001) when compared with other tertiles of MIS. ROC curve analysis of MIS showed 56.5% sensitivity and 81% specificity in predicting death rate (AUC 0.709; 95% CI 0.604-0.815, p < 0.001). Kaplan-Meier survival analysis showed MIS ≥7 had a strong association (log rank test, p < 0.001) with mortality during 36 and more months of follow-up time. In unadjusted analyses, MIS (HR 1.140; 95% CI 1.054-1.233; p < 0.05) and HsCRP (HR 2.369; 95% CI 1.779-3.154; p < 0.001) found to be predictors of mortality. MIS and HsCRP remained predictors of mortality even after adjustments., Conclusions: This study shows MIS is an important factor that determines mortality in pre-dialysis CKD patients during 36 and more months of follow-up time. Patients with MIS ≥7 have high risk for mortality and needs close monitoring. In clinical setting application of MIS has a greater utilization in pre-dialysis CKD patients. Further research with longitudinal assessment of MIS and its association with outcomes are warranted. Pre-dialysis CKD patients should be assessed for their nutritional status and inflammation using MIS regularly to prevent malnutrition and its associated complications through appropriate medical and nutritional intervention., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Major burn patients are characterized by large exudative losses of Cu, Se and Zn. Trace element (TE) repletion has been shown to improve clinical outcome. Having increased the TE doses over time, the study aimed at analysing if our repletion protocol corrected TE plasma concentrations and if the necessity for continuous renal replacement therapy (CRRT) might increase the TE needs., Methods: Retrospective analysis of prospectively collected data in burn patients requiring intensive care (ICU) between 1999 and 2015., Inclusion Criteria: Admission on day 1, full treatment, burned surface area (TBSA) ≥20% and ≥1 TE plasma determination during the stay. Four groups were constituted according to protocol changes. Period 1 (P1): 1999-2000, P2: 2001-2005, P3: 2006-2010, P4: 2011-2015. Changes consisted in increasing TE repletion doses and duration. Demographic data, daily TE intakes and weekly plasma concentrations were retrieved for the first 21 ICU-days. Data as median (IQR)., Results: 139 patients completed the criteria, aged 37 (28) years, burned on 35 (25) % TBSA. As a result of prescription, Cu, Se and Zn intakes increased significantly between P1 and P4, resulting in normalization of plasma Cu (16 μmol/l) since P3 and Zn (13.5 μmol/l) since P2. Median plasma Se were above reference range (1400 nmol/l) during P3 and P4. CRRT patients required higher doses of Cu for maintenance within normal ranges., Conclusion: This dose finding study shows that the latest repletion protocol is safe and normalizes Cu and Zn concentrations. Se doses result in supra-normal Se concentrations, suggesting prescription reduction. CRRT patients are at high risk of Cu depletion and require specific monitoring., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Malnutrition is a prevalent condition in older inpatients and has been shown to increase morbidity and direct medical costs. A number of established tools to assess malnutrition are available but malnourished patients rarely receive adequate nutritional assessment and treatment. The medical and economic consequences of malnutrition in hospitalized patients are therefore often underestimated. This study investigates whether the Geriatric Nutritional Risk Index (GNRI) predicts hospital mortality, correlates with length of hospital stay (LOS) and inflammatory markers in older inpatients., Methods: We conducted a prospective monocentric study in 500 hospital patients over 65 years of age (female: 248; male: 252; age: 76.3 ± 0.31 years). GNRI was correlated to C-reactive protein (CRP), lymphocyte count, LOS and all-cause mortality, adjusted for potential confounders., Results: The median body mass index was 24.1 (25th percentile: 21.1; 75th percentile: 27.8) kg/m 2 and the mean GNRI 82.2 ± 0.56. A higher risk GNRI was associated with increased CRP levels (p < 0.05) and low lymphocyte counts (p < 0.05) after multivariable adjustment. Moreover, we found positive correlation between a higher risk GNRI and length of hospital stay, whereas, the association with in-hospital mortality was not significant., Conclusions: The GNRI correlates well with indicators of inflammation and the length of hospital stay. The routine implementation of the GNRI for the nutritional assessment of older patients could have a significant medical and socio-economic impact., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The assay of plasma transthyretin (TTR), also known as prealbumin, is a key step in the assessment of nutritional status. However, it remains unclear whether it really is a useful nutrition marker, and when and how to use it and interpret TTR levels and variations. Risk of malnutrition, malnutrition severity, prognosis associated with malnutrition and effectiveness of refeeding are four parameters in nutritional assessment, and need clear separation to understand the associated utility of TTR. TTR does not have the same impact and potential on each of these parameters: it can be helpful but not essential for evaluating the risk of malnutrition, and it can diagnose malnutrition and its severity in patients with no inflammation syndrome. TTR is a good marker for prognosis associated with malnutrition, and is even better for monitoring refeeding efficacy despite inflammation. Thresholds depend on the purpose for which it is used. We propose a simple algorithm to guide the interpretation of TTR levels as a helpful tool for day-to-day practice., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aim: Sarcopenia, the age-related decrease in muscle mass, strength, and function, is a main cause of reduced mobility, increased falls, fractures and nursing home admissions. Cross-sectional and prospective studies indicate that sarcopenia may be influenced in part by reversible factors like nutritional intake. The aim of this study was to compare functional and nutritional status, body composition, and quality of life of older adults between age and sex-matched older adults with and without sarcopenia., Methods: In a multi-centre setting, non-sarcopenic older adults (n = 66, mean ± SD: 71 ± 4 y), i.e. Short Physical Performance Battery (SPPB): 11-12 and normal skeletal muscle mass index, were recruited to match 1:1 by age and sex to previously recruited adults with sarcopenia: SPPB 4-9 and low skeletal muscle mass index. Health-related quality of life, self-reported physical activity levels and dietary intakes were measured using the EQ-5D scale and index, Physical Activity Scale for the Elderly (PASE), and 3-day prospective diet records, respectively. Concentrations of 25-OH-vitamin D, α-tocopherol (adjusted for cholesterol), folate, and vitamin B-12 were assessed in serum samples., Results: In addition to the defined components of sarcopenia, i.e. muscle mass, strength and function, reported physical activity levels and health-related quality of life were lower in the sarcopenic adults (p < 0.001). For similar energy intakes (mean ± SD: sarcopenic, 1710 ± 418; non-sarcopenic, 1745 ± 513, p = 0.50), the sarcopenic group consumed less protein/kg (-6%), vitamin D (-38%), vitamin B-12 (-22%), magnesium (-6%), phosphorus (-5%), and selenium (-2%) (all p < 0.05) compared to the non-sarcopenic controls. The serum concentration of vitamin B-12 was 15% lower in the sarcopenic group (p = 0.015), and all other nutrient concentrations were similar between groups., Conclusions: In non-malnourished older adults with and without sarcopenia, we observed that sarcopenia substantially impacted self-reported quality of life and physical activity levels. Differences in nutrient concentrations and dietary intakes were identified, which might be related to the differences in muscle mass, strength and function between the two groups. This study provides information to help strengthen the characterization of this geriatric syndrome sarcopenia and indicates potential target areas for nutritional interventions., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Understanding mature breastmilk immunology may benefit infants chronically exposed to infectious pathogens in resource-limited regions., Methods: This prospective rural/semi-rural Tanzanian cohort of women (n = 102 at delivery; 38% HIV-positive) and their infants (n = 102) investigated breastmilk, maternal and infant serum immunoglobulins (IgA/IgG1-4/IgM) and cytokines (IL-1β/IL-2/IL-6/IL-10/IL-12p70/IL-13/IL-15/TNF-α/IFN-γ) at 1, 2, 3, 6-months postpartum., Results: Milk immunoglobulins followed an inverse U-shaped pattern, while cytokine patterns were mixed. Exclusive breastfeeding duration and feeding intensity were associated with greater breastmilk total immunoglobulin and IgA, IgG1-3 and IL-12p70 concentrations. Maternal mastitis, fever or cough was associated with higher breastmilk total cytokine concentrations, while infant fever was associated with lower milk immunoglobulins or cytokines. Strong (r ≥ 0.40) to weak (r = 0.20-0.29) positive correlations between maternal serum-breastmilk or breastmilk-infant serum immunoglobulins were evident. Breastmilk cytokines were moderate to weakly negatively correlated with infant serum. Breastmilk immunology did not differ by maternal malnutrition or HIV-seropositivity., Conclusions: Mature breastmilk is a dynamic source of many specific and non-specific immune factors associated with maternal and infant health and infant nutrition. Breastfeeding practices are associated with differential breastmilk immunological composition providing immunological support for universal recommendations to exclusively breastfeed for 6-months., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Optimization of the refeeding strategy for the management of malnutrition in early life may enable to improve the quality of catch-up growth. While some data suggest better assimilation of peptides rather than whole proteins the evidence are scarce., Objective: To compare the nutritional properties of peptides, partially hydrolyzed proteins or whole proteins in food-deprived/refed young rats., Methods: Male SD rats (n = 109, 60-70 g) were food-deprived for 48 h and refed for 2-13 days. According to the set of experiments, refeeding was performed at 90% or 100% basal spontaneous intake or ad libitum with either peptide-, partially hydrolyzed protein- or whole protein-containing pediatric enteral nutrition formulas. Body weight, caloric intake and nitrogen balance were measured daily, intestinal trophicity was measured after two-day refeeding, and body composition was determined at the end of the refeeding period., Results: A 2-day food deprivation in young rats led to significant body and organ weight losses, alterations of gut morphology, and decreased plasma citrulline, a marker of gut function. A cautious 2-day renutrition at 90% pre-deprivation level did not restore nutritional status whatever the form of nitrogen supply. Ad libitum feeding was shown to be feasible with improved nitrogen efficiency. After 13 days, compared to chow diet, body weight gain was the lowest with peptide- and whole protein-containing diets, and significantly improved with partially hydrolyzed proteins with limited improvement in body lean mass (+8%, NS). Additional experiments indicated that in this model it will be necessary to significantly increase nitrogen supply in order to restore initial body weight and lean body mass., Conclusions: Our results show benefits of ad libitum refeeding on catch-up growth. Our data suggest that partially hydrolyzed proteins may be beneficial in terms of body weight gain but that probably their effectiveness may be improved with higher nitrogen supply., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Malnutrition is common in patients with active tuberculosis (TB), yet little information is available on serial dietary intake or body composition in TB disease., Objective: To evaluate macronutrient intake and body composition in individuals with newly diagnosed TB over time., Design: Adults with active pulmonary TB (n = 191; 23 with multidrug resistant TB (MDR-TB) and 36 culture-negative household contacts (controls) enrolled in a clinical trial of high-dose cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index (BMI; kg/m(2)) and bioelectrical impedance analysis (BIA) to estimate fat mass and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes over time and linear regression were used., Results: At baseline, mean daily energy, protein, fat and carbohydrate (CHO) intakes were significantly higher, and body weight, BMI, fat-free mass and fat mass were significantly lower, between TB subjects and controls. These remained significant after adjusting for age, gender, employment status and smoking. In all TB subjects, baseline mean daily intakes of energy, fat and protein were adequate when compared to the US Dietary Reference Intakes and protein significantly increased over time (p < 0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB patients exhibited lower body weight and fat-free mass over time, despite similar daily intake of kcal, protein, and fat., Conclusions: Macronutrient intake was higher in TB patients than controls, but TB-induced wasting was evident. As macronutrient intake of TB subjects increased over time, there was a parallel increase in BMI, while body composition proportions were maintained. However, individuals with MDR-TB demonstrated concomitantly decreased body weight and fat-free mass over time versus drug-sensitive TB patients, despite increased macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient intake, likely reflecting the catabolic effects of TB., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: Evaluation of potential associations between plasma glutamine levels and the incidence of cancer related fatigue, physical performance, poor nutritional status, and inflammation in patients with solid tumors., Study Design: Mono-center cross-sectional study recruiting 100 (34 women) consecutive patients (September 2009-March 2011; ≥18 y) with solid tumors and causal tumor therapy., Methodology: Fasting venous blood was harvested for routine clinical chemistry, amino acid (HPLC) and inflammation marker analyses. Clinical assessments included global, physical, affective and cognitive fatigue (questionnaire) and Karnofsky performance status. Nutritional status was evaluated using bioelectrical impedance analysis, the Prognostic Inflammatory and Nutritional Index and plasma protein levels. Regression analyses were performed to correlate continuous variables with plasma glutamine (95% confidence intervals)., Results: Nutritional status was impaired in 19% of the patients. Average plasma glutamine concentration (574.0 ± 189.6 μmol/L) was within normal range but decreased with impaired physical function. Plasma glutamine was linked to the ratio extracellular to body cell mass (p < 0.044), CRP (p < 0.001), physical (p = 0.014), affective (p = 0.041), and global fatigue (p = 0.030). Markers of inflammation increased with low physical performance., Conclusions: The data support our working hypothesis that in cancer patients systemic inflammation maintains a catabolic situation leading to malnutrition symptoms and glutamine deprivation, the latter being associated with cancer related fatigue., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Malnutrition can significantly affect clinical outcomes in critically ill children. In view of the limitations of anthropometry, nutrition-related serum biomarkers have been used to assess the degree of malnutrition in the pediatric intensive care unit. The aim of this review is to critically appraise the use of nutrition-related serum biomarkers in predicting clinical outcomes in critically ill children., Methods: We searched major databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) using MeSH terms and key words related to "biomarkers", "nutrition" and "critically ill children". All studies that explored the relationship between any nutrition-related serum biomarker and clinical outcomes in critically ill children (1 day-18 years) were included. The clinical outcomes of interest were duration of intensive care unit or hospital stay, duration of mechanical ventilation and mortality., Results: We found one randomized controlled trial and 15 observational studies involving 2068 children. In these 16 studies, 16 different nutritional biomarkers and two nutrition indices were examined. Albumin (n = 7), magnesium (n = 4), transferrin, prealbumin and calcium (n = 3 respectively) were the most commonly studied biomarkers. Seven biomarkers (25-hydroxyvitamin D, albumin, calcium, magnesium, total protein, transferrin, triglycerides) and two indices (modified nutritional index and Onodera's prognostic nutritional index) had positive associations with clinical outcomes. However, no biomarkers or nutrition indices consistently predicted clinical outcomes., Conclusions: Current medical literature does not provide convincing data to demonstrate any association between nutrition-related serum biomarkers and clinical outcomes in critically ill children. Further research is required to identify novel and clinically robust nutrition-related biomarkers., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Malnutrition is associated with poorer outcome in cystic fibrosis (CF). This follow-up study aimed to document nutritional status changes, including fat-free mass (FFM), in adults with CF; and to identify predictors of FFM loss., Methods: Fifty-eight non-transplanted CF adults (mean ± SD forced expiratory volume in one second (FEV1) 63.7 ± 21.4%predicted; mean ± SD age 30.3 ± 7.7years at baseline) were studied at baseline and 3.6 ± 0.4 years later. Body composition was measured using dual-energy X-ray absorptiometry. At follow-up, blood was analysed for interleukin-6 and tumour necrosis factor-α (TNF-α) on three occasions over six months and averaged for each participant. Associations with annual percentage change in FFM (ann%ΔFFM), including cytokines, CF genotype and annual change in FEV1%predicted (annΔFEV1%), were determined., Results: Mean FFM was 49.5 ± 8.8 kg at baseline and 49.6 ± 8.9 kg at follow-up (p = 0.66). Ann%ΔFFM ranged from -2.0 to +3.6%. FEV1%predicted declined by 1.2 ± 2.4% per year. Forty percent of participants had elevated average interleukin-6 levels. Ann%ΔFFM was negatively correlated with interleukin-6 levels (rho -0.34, p = 0.008), but not TNF-α or annΔFEV1%. F508DEL homozygote or heterozygote participants had greater FFM loss than those carrying no F508DEL allele (p = 0.01)., Conclusion: Higher serum interleukin-6 and presence of the F508DEL mutation, but not TNF-α, were associated with FFM loss in adults with CF., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Older adults are poorly assessed for malnutrition risk although malnutrition is not an uncommon problem in this population. The aim of this study was to determine the malnutrition risk and its correlates in geriatric outpatients., Method: The study was performed in 2327 patients > or =65 years old who were admitted to our Geriatric Medicine outpatient clinic. Together with comprehensive geriatric assessment, nutritional assessment with short version of mini nutritional assessment test (MNA-SF) was performed. MNA-SF score < or =11 was determined as malnutrition risk., Results: Mean age of patients was 72.14+/-6.11 and 1479 (63.6%) were female. Mean MNA-SF score was 12.31+/-2.18. The number of patients with MNA-SF score < or =11 was 651 (28%). Depression, haematocrit, plasma fasting glucose, albumin, erythrocyte sedimentation rate, instrumental activities of daily living scores and bone mineral density measured from total femur were found to be significantly associated with malnutrition risk., Conclusion: In this study malnutrition risk was detected in 651 (28%) patients. This ratio was similar to the literature. In older adults malnutrition risk is found to be increased due to majority of chronic illnesses and physical dependency. In conclusion, nutritional assessment should be a part of comprehensive geriatric assessment., (Copyright 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Backgrounds & Aims: Malnutrition is a prominent feature of tuberculosis. Little is known about the role of the appetite-related hormones, ghrelin and leptin, in malnutrition in tuberculosis. This study was undertaken to determine whether ghrelin and leptin contribute to malnutrition in active pulmonary tuberculosis., Methods: Nutritional parameters and plasma levels of ghrelin, leptin, and inflammatory cytokines were measured before treatment and after clinical improvement following anti-tuberculosis chemotherapy in 23 tuberculosis subjects and 23 healthy controls prospectively. Patients were divided into well-nourished (n=15) and malnourished (n=8) groups., Results: Ghrelin but not leptin levels were significantly lower in the malnourished tuberculosis group than in the well-nourished tuberculosis group [44.0 (43.0-54.0) vs. 122 (108-158)pg/mL; p<0.05]. Malnutrition score was negatively correlated to ghrelin (rho=-0.76, p<0.01) but not to leptin levels. TNF-alpha and IL-6 levels were significantly higher in the malnourished tuberculosis group than in the well-nourished tuberculosis group and controls. Plasma levels of ghrelin tended to decrease as inflammatory cytokines increased before treatment., Conclusions: Decreased plasma ghrelin levels, in addition to increased plasma inflammatory cytokine levels, may be associated with malnutrition in active pulmonary tuberculosis., (Copyright 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Anorexia is frequent in the malnourished elderly. We studied the effects of age, nutritional status and refeeding on the expression and secretion of the orexigenic peptide ghrelin., Methods: Four groups were prospectively enrolled: 11 undernourished elderly (80+/-6 y, BMI: 17.4+/-1.9 [Mean+/-SD]), nine well-nourished elderly (76+/-9 y, 23.5+/-2.0), 10 undernourished young (26+/-6 y, 15.1+/-1.9) and 10 well-nourished young (34+/-8 y, 22.2+/-2.7). Fasting and postprandial plasma ghrelin and other hormones (every 30 min) were measured at baseline and after a 21-day enteral nutrition in malnourished patients. Gastric ghrelin mRNA levels were measured by RT-PCR at baseline in all subjects., Results: Ghrelin was significantly higher in undernourished (2151+/-871 ng/L) than in well-nourished (943+/-389 ng/L) adults, whereas there were no differences between undernourished (1544+/-758 ng/L) and well-nourished (1154+/-541 ng/L) elderly. Refeeding did not influence ghrelin levels. Gastric ghrelin mRNA levels were similar in all groups., Conclusions: There is an absence of malnutrition-induced increase of plasma ghrelin levels in elderly subjects. This feature, post-transcriptional, may be important in the lack of adaptation of elderly subjects to malnutrition.

Background & Aims: Patients who have neurological dysphagia induced by cerebrovascular disease are at high risk of malnutrition and aspiration pneumonia. Since trace elements in serum bind to serum protein, serum trace elements concentration is influenced by serum protein concentration. In addition, serum protein concentration is influenced by malnutrition and inflammation. Therefore, evaluation of serum trace elements concentration has to consider influence of malnutrition and inflammation. In recent years, enteral formula including rich trace elements were developed to prevent trace elements deficiency. However, serum trace elements concentration showed a low level even if patients were receiving enough trace elements intake. We thought that it was effective in nutritional management of patients with malnutrition and inflammation to clarify about correlation among nutritional indices, serum trace elements, and the amount of trace element intake in tube-fed patients. In this study, we aimed to determine nutritional indices that are predictors of serum trace elements in patients with neurological dysphagia on long-term tube feeding., Methods: Subjects were 40 elderly bedridden patients with neurological dysphagia induced by cerebrovascular disease. All subjects were fed total enteral nutrition via nasogastric tube. We investigated serum trace elements (iron, copper, zinc) and nutritional indices (body mass index, albumin, transferrin, ceruloplasmin, C-reactive protein, hemoglobin, lymphocyte, trace elements intake), and analyzed by multiple regression analysis. In addition, we divided subjects into two groups based on inflammatory response. The first group was 20 patients with inflammation (inflammation group), and another group was 20 patients without pneumonia (control group)., Results: Subjects were malnourished and showed inflammatory response: low body weight (55%), hypoalbuminemia (58%), moderate or severe inflammation (53%), anemia (38%). Ratio of low serum iron concentration was 43%. Ratio of high serum copper concentration was 45%. Ratio of low serum zinc concentration was 65%. Mean of trace elements intake was slightly more than requirements. In multiple regression analysis in all subjects, predictor of serum iron was hemoglobin (P<0.01) and transferrin (P<0.05), predictor of serum copper was ceruloplasmin (P<0.001) and C-reactive protein (P<0.05), predictor of serum zinc was albumin (P<0.05). In comparisons of nutritional status between inflammation group and control group, serum zinc concentration in inflammation group was significantly lower than control group. On the other hand, ceruloplasmin, C-reactive protein and serum copper concentration in inflammation group were significantly higher than control group. There was no significant difference in daily trace elements intake between inflammation group and control group., Conclusion: In tube-fed patients with neurological dysphagia, serum trace elements concentration was influenced by malnutrition and inflammation. It was suggested that serum trace elements concentration might not be normalized if malnutrition and inflammation are not treated. We recommend periodical monitoring of trace elements for long-term tube-fed patients with neurological dysphagia.

Objective & Aims: The present study aimed at retrospectively evaluating the incidence of mortality and major and minor postoperative complications in patients who underwent surgery for gastric cancer between 2000 and 2006 stratified according to the preoperative percentage weight loss, serum albumin levels and body mass index (BMI)., Methods: One hundred and ninety-six patients affected by gastric cancer admitted to the Division of Digestive Surgery of the Catholic University of Rome between January 2000 and December 2006 were considered eligible and were included in the study. According to the weight loss, patients were divided into three groups: (1) 0-5%; (2) 5.1-10%; (3) >10%. On the basis of serum albumin levels, were divided into three groups: (1) <3.0 g/dl; (2) 3.0-3.4 g/dl; (3) >3.5 g/dl. According to BMI, were divided into four groups: (1) <18.5 kg/m(2); (2) 18.5-24.9 kg/m(2); (3) 25.0-29.9 kg/m(2); (4) >30.0 kg/m(2). Postoperative complications and mortality were reported. Complications were classified by objective criteria as major or minor, and as infectious or non-infectious., Results: The postoperative mortality was 0%. Major infectious complications occurred in 20 patients (10.2%), major non-infectious in 18 (9.2%), minor infectious in 21 (10.7%), whereas minor non-infectious complications were absent. The rate of major infectious, major non-infectious and minor infectious postoperative complications was similar in patients with absent or light weight loss (8.8%, 8.8%, 10.6%, respectively), mild weight loss (15.3%, 11.5%, 9.6%, respectively), or severe weight loss (6.4%, 6.4%, 12.9%, respectively). Similarly, the rate of postoperative complications did not differ between patients with serum albumin <3.0 g/dl (10.8%, 8.1%, 8.1%, respectively); between 3.0 and 3.4 (8.8%, 13.3%, 17.7%, respectively) or > or =3.5 g/dl (10.5%, 7.9%, 8,7%, respectively). According to BMI, the rate of postoperative complications was: 11.7%, 5.8%, and 5.8% for BMI <18.5 kg/m(2); 9.4%, 8.2%, and 11.7% for BMI between 18.5 and 24.9 kg/m(2); 10.7%, 10.7%, and 9.2% for BMI between 25 and 29.9 kg/m(2); 10.3%, 10.3% and 13.7% for BMI >30 kg/m(2). Then, we evaluated the postoperative morbidity only in patients who underwent total gastrectomy or distal subtotal gastrectomy associated with extended lymphadenectomy. In this group of patients, the rate of postoperative complications was comparable in patients with 0-5% (8.8%, 7.7%, 10%, respectively), 5.1-10% (14.6%, 9.7%, 9.7%, respectively), and >10% (7.1%, 7.1%, 14.3%, respectively) weight loss. Also stratifying the patients according to the serum albumin levels, the rate of postoperative complications did not differ significantly (serum albumin <3.0 g/dl: 14.8%, 11.1%, 14.8%, respectively; serum albumin between 3.0 and 3.4 g/dl: 6.2%, 12.5%, 15.6%, respectively; serum albumin > or =3.5 g/dl: 10.4%, 5.8%, 7.0%, respectively). According to BMI, the rate of postoperative complications was: 7.6%, 0%, and 7.6% for BMI <18.5 kg/m(2); 9.5%, 9.5%, and 11.1% for BMI between 18.5 and 24.9 kg/m(2); 12.5%, 8.3%, and 10.4% for BMI between 25 and 29.9 kg/m(2); 9.5%, 9.5% and 9.5% for BMI >30 kg/m(2)., Conclusion: The present study suggests that weight loss and hypoalbuminemia are not associated with an increased risk of mortality and morbidity in patients who underwent surgery for gastric cancer. This study may represent a stimulus for further studies aiming at evaluating the actual role of malnutrition in the development of postoperative complications in major abdominal surgery.

Background & Aims: The aim of our study was to examine, in patients with gastric cancer, the correlation between nutritional status, QoL (quality of life) and serum levels of TNF-alpha, IL-1 and IL-6., Methods: Forty-eight patients with gastric cancer were included. Nutritional status was assessed by % of weight loss in the previous 1 and 6 months, Patient-Generated Subjective Global Assessment, bioelectrical impedance analysis and by dynamometry. QoL was assessed by EORTC QLQ-C30 questionnaire. TNF-alpha, IL-1 and IL-6 serum concentrations were determined using an ELISA assay., Results: Prevalence of malnourished patients varied between 30% and 75% according to various methods used. QoL scores were significantly worse in patients with more advanced disease and in malnourished ones. Malnourished patients had higher values of IL-1 and TNF-alpha (16.7 and 28.0 pg/ml), p<0.05 and p<0.001. QoL was significantly worse in patients with higher levels of IL-1 and TNF-alpha (p<0.01 and p<0.001, respectively). A TNF-alpha cut-off value of 8.72 pg/ml was associated with higher risk of malnutrition (MN) according to PG-SGA (94% sensitivity, 93% specificity). No correlation was observed with perioperative complications., Conclusions: The prevalence of MN is high in patients with gastric cancer. A significant correlation was found between higher values of cytokines, especially TNF-alpha, MN and QoL.

Background and Aims: Although serum albumin is well known as a marker of nutritional status, it has remained unclear whether impaired physical function affects serum albumin concentrations in older people. We examined whether hypoalbuminemia can be used as a marker of malnutrition in elderly subjects with various levels of physical impairment., Methods: A total of 262 elderly subjects without acute illness were enrolled from various geriatric settings. For the nutritional assessment, serum albumin, total cholesterol, anthropometric measurements, and subjective global assessment (SGA) were determined. Physical function was evaluated by rating score of activity of daily living (ADL)., Results: As a whole, participants' serum albumin levels correlated with various nutritional parameters including anthropometric measurements and levels of serum total cholesterol as well as the SGA evaluation. However, after adjusting for age and gender, serum albumin levels in participants with a low ADL function did not correlate with nutritional parameters. Approximately 80% participants with low ADL function who were evaluated as being well nourished according to SGA evaluation had serum albumin levels lower than 35 g/l., Conclusions: The utility of serum albumin and the traditional cutoff (35 g/l) in older people with low ADL function is questionable even among those without inflammation.

Background & Aims: Malnutrition is a widespread but largely unrecognized problem in aged people. Although absolute total lymphocyte count (TLC) has been proposed as a useful indicator of nutritional status, there is little evidence that low TLC levels reflect malnutrition in the elderly. To examine whether TLC is a suitable marker of malnutrition in the elderly., Methods: A total of 161 elderly subjects (44 males and 117 females, mean age+/-SD: 77.9+/-7.4; range: 65-95 years) were enrolled from geriatric clinical settings. The participants were categorized according to severely low, low, or normal TLC. Anthropometry measurements, serum albumin, total cholesterol levels, and total score on the mini-nutritional assessment (MNA) were determined., Results: There were no significant differences among the three TLC groups with regard to anthropometry measurements, serum albumin, total cholesterol levels, or MNA score. There was a significant negative correlation of TLC with age, but not with other nutritional markers. The clinical nutritional screening tool, MNA score, was well correlated with all of the nutritional parameters used in the present study except for TLC., Conclusion: TLC is not a suitable marker of malnutrition in the elderly.

Background & Aims: Malnutrition is common in patients with end-stage liver disease and is a risk factor for post-transplant morbidity. The goal of this study was to assess the safety of an immune-enhancing diet in patients undergoing liver transplantation and to investigate its effects on nutritional status., Methods: Fifteen consecutive patients received oral Impact (0.6l/d) for a median 54 (range 10-168)d pre-transplant and enteral Impact was started early after transplant. Total body protein was measured prior to commencing supplemental Impact, immediately prior to transplant and 10, 15, 30, 90, and 180 days post-transplant. The results were compared with those from 17 patients who received standard nutritional intervention., Results: All study patients tolerated Impact pre- and postoperatively and there were no safety concerns. Over the preoperative period total body protein increased significantly (P = 0.017). In 7 patients followed for 6 months post-transplant, a significant (P = 0.026) loss of body protein occurred over the first 15 postoperative days which was regained by 6 months. In the patients who did not receive Impact, body protein did not change preoperatively and the loss after surgery was not regained. Infectious complications occurred in 5/15 (33%) Impact patients and 12/17 (71%) non-Impact patients (P = 0.074)., Conclusions: In patients with end-stage liver disease, our results suggest the possibility that Impact may have a role in improving preoperative nutritional status, hastening recovery after transplant, and reducing postoperative infectious complications. These potential benefits need to be confirmed in a randomised controlled trial.