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Objective(s): Malnutrition and protein-energy wasting are associated with morbidity and mortality in hemodialysis patients. Existing nutritional scores rely primarily on cross-sectional data. Using readily available nutritional indicators, we developed models to predict the risk of mortality and hospitalization in prevalent hemodialysis patients., Design and Methods: In this retrospective study, we constructed prediction models of 1-year mortality and hospitalization using generalized linear models, generalized additive models (GAM), classification tree, and random forest models. The models were compared using area under the receiver-operating characteristics curve (AUC) and calibration curves. Model predictors included nutritional and inflammation indicators, demographics, comorbidities, and slopes of all continuous variables over 6 months. Patients were randomly split in the ratio 2:1:1 into training, testing, and validation cohorts, respectively. We included patients with hemodialysis vintage ≥1 year from Fresenius Medical Care North America clinics from July 2011 to December 2012 (N = 21,802 in mortality analysis; N = 13,892 in hospitalization analysis).The outcome variables were 1-year mortality and hospitalization., Results: For mortality prediction, GAM was the best model (AUC = 0.85, 95% confidence interval = 0.83-0.86), comprised of neutrophil-to-lymphocyte ratio slope, serum bicarbonate slope, and vintage as nonlinear predictors, and age, serum albumin, and creatinine as linear predictors. For hospitalization prediction, GAM was also the best model (AUC = 0.70, 95% confidence interval = 0.62-0.79) and included neutrophil-to-lymphocyte ratio slope, bicarbonate slope, volume of urea distribution, vintage, and phosphate slope as nonlinear predictors, in addition to albumin, congestive heart failure, age, phosphate, equilibrated normalized protein catabolic rate, and creatinine as linear predictors. Both models demonstrated good calibration, with mild overestimation of hospitalization risk at the highest risk interval., Conclusions: The GAM model can accurately predict the risk of mortality and hospitalization. Application of these prediction models could inform allocation of nutritional interventions to patients at highest nutritional risk., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Oral manifestations of deficiency of iron, vitamin B12 and folic acid are thought to be common. Prevalence of these deficiencies among patients with compatible symptoms is not well known. The goal of this study was to summarize evidence from a dental practice of iron, vitamin B12 and folic acid deficiency in patients presenting with compatible oral manifestations., Methods: 250 patients who presented with burning mouth syndrome, angular cheilitis, recurrent aphthous stomatitis, papillar atrophy of the tongue dorsum or mucosal erythema were identified. Patients underwent clinical examination, and the blood samples were taken., Results: 250 patients (208 females; 42 males, mean age 44.1 years) with at least one corresponding symptom or sign were identified. The nutritional deficiency of one or more nutrients was found in 119 patients (47.6%). Seven times more females than males were noted to have one type of deficiency (104 females, 15 males). Iron deficiency as defined was diagnosed in 62 patients (24.8%), vitamin B12 or folic acid deficiency in 44 patients (17.6%) and both deficiencies (iron + vitamin B12/folic acid) in 13 patients (5.2%). The only predictive factor was gender and only for iron deficiency. The presence of more than one deficiency was noted in 10 patients (4.9%)., Conclusion: The most commonly observed deficiency in dental practice over the course of 11 years was an iron deficiency in the female population. Age, diet and reported co-morbidities did not show statistically significant predictable value in recognizing these deficiencies.

Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.

Objectives: This study aimed to analyze and evaluate serum insulin-like growth factor-binding protein 2 (IGFBP2) levels as a new biomarker of severe malnutrition in patients with advanced lung cancer. Design and methods: This prospective study involved 59 patients with advanced lung cancer. We detected serum IGFBP2 level by using enzyme-linked immunosorbent assay and analyzed its relationship to clinical characteristics, nutritional status, Glasgow prognostic score (GPS), and survival. Serum albumin and C-reactive protein (CRP) levels were measured, and nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The best cutoff point value for serum IGFBP2 level was established using receiver operating characteristic analysis. Kaplan-Meier method was utilized to analyze the survival curves. Results: Serum IGFBP2 levels were elevated in patients with advanced lung cancer and severe malnutrition. The best cutoff value for serum IGFBP2 level was determined at 363 ng/ml, which could diagnose severe malnutrition with 73.3% sensitivity and 70.5% specificity and was found to be related to albumin, CRP, and GPS. Patients whose serum IGFBP2 levels were higher than 363 ng/ml had poor survival outcome. Conclusion: This study demonstrates the remarkably association between higher serum level of IGFBP2 and severe malnutrition, albumin, CRP, GPS, and survival. Hence, serum IGFBP2 level can be used as a potential biomarker for diagnosis of severe malnutrition in patients with advanced lung cancer.

Introduction: Objective: secondary malnutrition and systemic inflammation may impair growth and body composition in children and adolescents with chronic kidney disease (CKD). This association has been scantily studied, particularly in pre-dialytic stages. Our aim was to correlate growth and nutritional status indicators with the serum concentration of interleukine 6 (IL-6) and ultrasensitive C-reactive protein (CRP) in children with CKD. Methods: this was a prospective cross-sectional study in 29 children and adolescents aged 3-16 years with CKD, stages 3 or 4, in two third-level general hospitals. The outcome variables were height for age, body mass index, arm anthropometric indicators, plus lean mass/fat percentage by bioelectrical impedance. The independent variables were IL-6 and CRP. This study was reviewed and approved by the Health Research and Ethics Committees of both hospitals. Results: height for age, body mass index, subscapular skinfold, arm fat area, and lean mass had a significant negative correlation with IL-6. The height-for-age z-score had a negative correlation with CRP. IL-6 explained 15% to 35% of the variance in height for age and nutritional status indicators. CRP predicted 22% of height for age. One fifth of the patients had acute malnutrition, and one third were stunted. Muscle was the most affected compartment. Conclusion: IL-6 and CRP in children and adolescents with CKD in the pre-dialytic stage predicted one fifth and one third of the variance in acute and chronic malnutrition indicators. The frequency of acute malnutrition and impaired growth was clinically significant. Muscular mass deficit was a central component of malnutrition.

Background: The aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population., Methods: For this cross-sectional study, a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were evaluated., Results: DRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group (p < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O 2 consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1., Conclusions: Our results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.

Background: Malnutrition is a common problem among children with chronic liver diseases (CLD). We aimed to assess the nutritional status of children with CLD and to correlate the anthropometric indices with the severity of liver disease, liver function tests, insulin growth factor-1 (IGF-1) and 25-hydroxy vitamin D (25- OH D)., Methods: A total of 69 patients with CLD and 50 healthy controls (6 months - 6 years) were included in the study. Nutritional status was assessed by anthropometric indices expressed in standard deviation score (Z score), biochemical, hematological and clinical parameters., Results: We found 52.2% of CLD patients underweight by weight for age (W/A); 50.2% were stunted by height for age/ length for age (HAZ or LAZ); and 39% exhibited wasting by weight/height or (length) for age (W/HZ or W/LZ) z scores analysis. The mean values of z scores for all anthropometric parameters were significantly correlated with unconjugated and conjugated bilirubin and INR (p < 0.05), except HAZ or LAZ. Also, a significant correlation to albumin was found, except for W/HZ or (W/LZ) (p = 0.157). The z scores < - 2 SD based on W/ H versus arm indicators showed significant differences in MUAC, UAA and AMA (p < 0.001). We found no correlation between anthropometric z-scores and the mean IGF-1 and (25- OH D) values (p > 0.05). Malnutrition was directly correlated with the severity of hepatic dysfunction, particularly, Child-Pugh C cases. The mean IGF-1 and (25- OH D) values were significantly correlated with the severity of liver disease (p < 0.001)., Conclusions: Our results identified anthropometric arm indicators and MUAC/A measurements as an effective applied methods for assessing nutritional status in CLD children. Moreover, Integrating comprehensive clinical assessment, anthropometric measurements and objective biochemical analyses is essential for evaluation, follow-up and management of CLD children with variable degree of malnutrition.

Undernutrition, as described by low body mass index (BMI), is a foremost risk factor for the progression of active Tuberculosis (TB). Undernutrition is also known to impact the baseline frequencies of innate and adaptive immune cells in animal models. To verify whether undernutrition has any influence on the baseline frequencies of immune cells in latent Mycobacterium tuberculosis infection (LTBI), we examined the frequencies of T cell-, B cell, monocyte- and dendritic cell (DC)- subsets in individuals with LTBI and low BMI (LBMI) and contrasted them with LTBI and normal BMI (NBMI) groups. LBMI was characterized by decreased frequencies and absolute cell counts of T cells, B cells and NK cells in comparison with NBMI. LBMI individuals demonstrated significantly enhanced frequencies of naïve and effector CD4+ and CD8+ T cells and significantly decreased frequencies of central memory, effector memory CD4+ and CD8+ T cells and regulatory T cells. Among B cell subsets, LBMI individuals demonstrated significantly diminished frequencies of naïve, immature, classical memory, activated memory, atypical memory and plasma cells. In addition, LBMI individuals showed significantly decreased frequencies of classical monocytes, myeloid DCs and plasmacytoid DCs and significantly increased frequencies of intermediate and non-classical monocytes and myeloid derived suppressor cells. BMI exhibited a positive correlation with B cell and NK cell counts. Our data, therefore, demonstrates that coexistent undernutrition in LTBI is characterized by the occurrence of a significant modulation in the frequency of innate and adaptive immune cell subsets., Competing Interests: The authors have declared that no competing interests exist.

This review was written to update the review that we published in Nutrition Research in 2007 by examining studies published in the last 11 years which describe the effects of trace mineral deficiencies and micronutrient supplementation on HIV infection and its progression. In addition, we included studies that explore the interactions between Highly Active Anti-Retroviral Therapy (HAART) and micronutrient nutrition, focusing on the essential trace minerals. This review summarizes the results described in relevant articles that were identified by literature searches conducted using the OVID Medline database. Four of the nine essential trace minerals, specifically chromium, iron, selenium, and zinc, can influence HIV progression and/or its treatment. Notably, copper-containing filters may prevent transmission of the HIV virus via breastfeeding. However, there is a lack of good evidence to date that fluoride, iodine, manganese, or molybdenum influence HIV infection. Recent studies reveal that HAART can alter serum trace mineral and vitamin concentrations, but the effects vary based on the medications used. Although they have contributed useful new data, the sample sizes for most of these studies were too small to draw definitive conclusions for introducing changes in the management of HIV infection. Larger studies are needed to better understand and define the roles of trace mineral and vitamin deficiencies and micronutrient supplementation in the management and treatment of HIV-infected patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The impact of vitamin D deficiency on the recovery of patients with malnutrition remains undefined. Our aim was to study the prevalence of vitamin D deficiency in a well-characterized cohort of patients with malnutrition and its association with outcomes.Within this secondary analysis of a randomized controlled trial, we examined the association of vitamin D deficiency and adverse clinical outcomes over a follow-up of 180 days in hospitalized patients at risk for malnutrition. We measured 25-hydroxyvitamin D levels upon admission and defined Vitamin D deficiency when levels were <50nmol/l. The primary endpoint was 180-day mortality.The prevalence of vitamin D deficiency in our cohort of 828 patients was 58.2% (n = 482). Patients with vitamin D deficiency had increased 180-day mortality rates from 23.1% to 29.9% (odds ratio 1.42, 95% confidence interval [CI] 1.03-1.94, P = .03). When adjusting the analysis for demographics, comorbidities, and randomization, this association remained significant for the subgroup of patients not receiving vitamin D treatment (adjusted odds ratio 1.63, 95% CI 1.01-2.62, P = .04). There was no significantly lower risk for mortality in the subgroup of vitamin D deficient patients receiving vitamin D treatment compared to not receiving treatment (adjusted odds ratio 0.74, 95% CI 0.48-1.13, P = .15).Vitamin D deficiency is highly prevalent in the population of malnourished inpatients and is negatively associated with long-term mortality particularly when patients are not receiving vitamin D treatment. Our findings suggest that malnourished patients might benefit from vitamin D screening and treatment in case of deficiency.

Objectives: To determine the impact of vitamin D deficiency and insufficiency on the development of anorexia in children with mild malnutrition without an obvious cause., Methods: This cross-sectional study was conducted in Faruk Medical City, Sulaymaniyah, Kurdistan Region, Iraq, between May and September 2018. It included 39 mildly malnourished children with a poor appetite for over 3 months and 156 children who were healthy except for minor illnesses as the control group. All the children were regular attendees at the outpatient clinic and were tested for serum levels of 25-hydroxy vitamin D. We used binary logistic regression statistical analysis to measure the significance of the association between vitamin D deficiency/insufficiency and anorexia with mild malnutrition in young children., Results: Of the 39 children in the anorexia group, 20 had vitamin D deficiency, and the remaining 6 had vitamin D insufficiency. On the other hand, 16 of the remaining children with normal appetites, showed a vitamin D deficiency, and 38 of them displayed insufficiency. Statistically significant association between vitamin D deficiency and anorexia with malnutrition was noted (odd ratio: 9.808; 95% confidence interval: 4.089 - 23.523; p=0.0001), while it was insignificant with vitamin D insufficiency. Conclusion: This study displayed a noteworthy relationship between vitamin D deficiency and anorexia with mild malnutrition in young children.

Solanum torvum (STO) and edible insects are potential dietary approaches to prevent malnutrition. Hence, we determined the effect of STO and insect powders on improving nutritional status in malnourished rats. Malnutrition was induced in rats by feeding 5% protein, ~2 ppm Fe (LPI) diet for 21 days. During the 14 day repletion, five groups of rats ( n = 8) were fed diets supplemented with Acheta domesticus (cricket, ADO), Rhynchophorus phoenicis fabricius (palm weevil larvae, RFA), STO, ADO + STO (TAD), and casein + ferrous sulfate (PIS, positive control), as well as a non-supplemented group (negative control, LPI). A normal (NOM) group was fed protein-Fe sufficient (PIS) diet throughout the study. Body composition was measured by Dual-energy X-ray absorptiometry. The hemoglobin (Hb) repletion method was used to assess relative biological value (RBV, compared to PIS) of the supplemented groups. No differences were found in weight gain, bone mineral content, lean and fat mass, and organ weights among the edible insects and PIS groups, but these results differed from STO and the LPI groups. An increase in Hb Fe and RBV with ADO and RFA was comparable to PIS. ADO and RFA could be excellent sources of protein and bioavailable Fe, making it a sustainable, low-cost food source to prevent malnutrition in humans.

Background: Increased levels of circulating heat shock protein 70 antibodies (anti-Hsp70) have been reported in hemodialysis (HD) patients. Since the anti-Hsp70 correlates with inflammation, it may associate with the malnutrition-inflammation score (MIS). The aim of this study was to determine whether the increased MIS score in HD patients are related to circulating levels of anti-Hsp70., Method: Ninety HD patients with an arteriovenous fistula, aged 30-65 years, who underwent three hemodialysis sessions a week for at least the past 3 months at a hemodialysis center were enrolled in this cross-sectional study. Patients were divided based on MIS score to two groups, and the clinical and biochemical variables were compared between them. MIS cutoff score of ≥ 5 indicated the presence of malnutrition. The association between categorized MIS and anti-Hsp70 was examined using regression models adjusted for diabetes mellitus, hemodialysis vintage, BMI, albumin, hs-CRP, IL6 and endotoxin levels as confounding factors., Results: The univariate regression analysis revealed a significant association between MIS ≥ 5 and hemodialysis vintage, uric acid, hs-CRP, IL-6, endotoxin and serum anti-Hsp70 level. After adjusting the confounders, the association between MIS ≥ 5 and serum anti-Hsp70 level remained significant., Conclusion: These data support the role of serum anti-Hsp70 in the development of malnutrition in HD patients. However, further studies with body composition assessments and better generalizability are required to investigate the association between nutritional status and circulating anti-Hsp70 level in HD patients.

Background and Objective: Treatment with oral antineoplastic agents known as tyrosine kinase inhibitors (TKIs) is new and, thus, little is known about their impact on nutritional status (NS), dietary intake, quality of life, and survival. The aim of this study was to provide information on these components in order to guide future nutritional recommendations., Patients and Method: A prospective, observational study in adults who start treatment with TKIs, in whom NS was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA), anthropometric measures, biochemical parameters, and dietary intake (24-hour dietary recall). The EORTC QLQ-C30 was used to assess quality of life. Nonparametric tests were used in statistical analysis, and survival was analyzed using Kaplan-Meier and log-rank curves., Results: Of the overall sample, 21.7% had moderate malnutrition according to PG-SGA, and 74.2% moderate weight loss at 6 months, but no patient had BMI<18.5kg/m 2 . Patients with moderate malnutrition had lower survival at four years of diagnosis (log-rank=0.015). Energy intake was lower than recommended by the ESPEN 2017 congress, and no patient covered the protein requirements (1.5g protein/kg weight) during follow-up. A worse score on the global health scale of the EORTC QLQ-C30 was related to worse NS., Conclusions: Treatment with TKIs does not appear to have a significant impact on NS and quality of life after 6 months of follow-up. Malnutrition should be prevented through individualized nutritional advice because it is related to shorter survival., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Relative energy deficiency in sport (RED-S) has been introduced as a broad-spectrum syndrome leading to possible dysfunction in numerous physiological systems, driven primarily by low energy availability (EA). Research in females has identified specific EA cut-points indicative of risk level for developing physiological and performance disturbances. Cut-points in males have yet to be evaluated. This study examined the prevalence of low EA in competitive (non-elite), recreationally trained (CRT) male endurance athletes. Materials and Methods : Subjects were 108 CRT (38.6 ± 13.8 y; 12.2 ± 5.4 h/wk training) male endurance athletes (runners, cyclists, triathletes) who completed a descriptive survey online via Qualtrics ® and returned 3 day diet and exercise training records. EA was calculated from returned surveys and training records. Resting metabolic rate (RMR) and lean body mass (LBM) were estimated from self-reported survey data. Prevalence of risk group was categorized based on the female cut-points: at risk (AR) ≤30 kcal/kg LBM, moderate risk (MR) = 30-45 kcal/kg LBM, or no risk (NR) ≥45 kcal/kg LBM. Results : In this sample, 47.2% ( n = 51) were classified as AR, 33.3% ( n = 36) as MR, and 19.4% ( n = 21) as NR for low EA. Cyclists had lower EA (26.9 ± 17.4 kcal/kg LBM, n = 45) than runners (34.6 ± 13.3 kcal/kg LBM, n = 55, p = 0.016) and all other sport categories (39.5 ± 19.1 kcal/kg LBM, n = 8, p = 0.037). Conclusions : The findings indicate this sample had a high prevalence of risk for low EA, at 47.2%. Only 19.4% of participants were at no risk, meaning ~80% of participants were at some degree of risk of experiencing low EA. Cyclists were at greater risk in this cohort of low EA, although why this occurred was unclear and is in need of further investigation. Future research should address whether the current female cut-points for low EA are appropriate for use in male populations., Competing Interests: The authors declare no conflict of interest.

The effect of inflammation on appetite and food intake has been rarely studied in humans. In this study, we examined the association of C-reactive protein (CRP), as an inflammatory marker, with appetite and food intake among older hospitalized patients. A total of 200 older individuals, who were consecutively admitted to a geriatric acute care ward, participated in this prospective observational study. Appetite was evaluated using the Edmonton Symptom Assessment System (ESAS) and the Simplified Nutritional Appetite Questionnaire (SNAQ), respectively. Food intake was measured according to plate diagram method and participants were categorized as having food intake <75% and ≥75% of meals served. Nutritional status was evaluated using the Mini Nutritional Assessment Short Form (MNA-SF). In addition, serum CRP was analyzed and the levels >3.0 (mg/dL) were considered as moderate to severe inflammation. Of total population with mean age 81.4 ± 6.6 years (62.5% females), 51 (25.5%) had no inflammation and 88 (44.0%) and 61 (30.5%) had mild and moderate to severe inflammation, respectively. According to MNA-SF, 9.0% and 60.0% had normal nutritional status or a risk of malnutrition, respectively, whereas 31.0% were malnourished. Based on the SNAQ-appetite-question, 32.5% of the patients demonstrated poor and very poor appetite whereas 23.5% reported severe loss of appetite according to ESAS. Ninety-five (48.0%) of the participants had food intake <75% of the meals offered. Significant associations between SNAQ-appetite ( p = 0.003) and ESAS-appetite ( p = 0.013) scores and CRP levels were observed. In addition, significant differences were observed in CRP levels between intake ≥75% and <75% of meals served ( p < 0.001). Furthermore, there were significant associations between appetite and nutritional status whereas malnourished older patients demonstrated a decreased appetite compared to those with normal nutritional status ( p = 0.011). In a regression analysis, inflammation was the major independent risk factor for patients' appetite ( p = 0.003) and food intake ( p = 0.011) whereas other variables such as infection ( p = 0.960), chronic inflammatory diseases ( p = 0.371), age ( p = 0.679) and gender ( p = 0.447) do not show any impact on appetite. Our findings confirm that poor appetite and low food intake are associated with inflammation in older hospitalized patients, suggesting that inflammation may contribute an important aspect to the development of malnutrition in these patients.

Cellular pathways such as inflammation or oxidative stress are the cause and triggers of disease-related malnutrition (DRM), but the influence of these markers on endoplasmic reticulum (ER) stress is unknown. The objective of this study was to analyze the relationship between mitochondrial function and ER stress parameters in a DRM population. The study population was composed of 82 outpatient subjects, of whom 45 were diagnosed with DRM and 37 were confirmed to be normonourished according to the American Society for Parenteral and Enteral Nutrition ASPEN criteria. We evaluated anthropometrical and biochemical parameters, pro-inflammatory cytokines in serum. Oxidative and ER stress markers were analyzed in leukocytes. DRM patients showed significant reductions in albumin and transferrin concerning the normonourished group, and also displayed higher levels of hsCRP, IL6, and TNFα, and the soluble adhesion molecules VCAM-1 and ICAM-1. Besides, oxygen consumption and mitochondrial membrane potential were reduced and Radical Oxygen Species ROS production was enhanced in DRM patients. In the case of ER markers, protein and mRNA expression revealed that CHOP, ATF6, and the P-eIF2α signal were enhanced in malnourished patients compared to control subjects. Correlation studies supported a relationship between weight loss and increased inflammation, mitochondrial dysfunction, and compromised function of the ER. Our results demonstrate that ER stress signaling pathways are influenced by inflammation and mitochondrial function in the leukocytes of a DRM population.

Background: Chromium is an essential trace metal that reduces oxidative stress and inflammation. In patients undergoing maintenance hemodialysis (MHD), a correlation among chromium exposure, inflammation, and malnutrition remains unclear. This study examined the possible effects of serum chromium levels (SCLs) in MHD patients., Methods: Initially, 732 MHD patients in dialysis centers were recruited. A total of 647 patients met the inclusion criteria and were stratified by SCL into four equal-sized groups: first quartile (< 0.29 μg/L), second quartile (0.29-0.56 μg/L), third quartile (0.57-1.06 μg/L), and fourth quartile (> 1.06 μg/L). Demographic, biochemical, and dialysis-related data were obtained for analyses. The analysis included nutritional and inflammatory markers., Results: As compared with the highest quartile group, more subjects in the lowest quartile group were of an older age; had lower hemoglobin and creatinine levels; had a higher prevalence of DM and malnutrition (serum albumin level < 3.6 g/dL); and higher serum transferrin saturation and ferritin levels. A stepwise multiple linear regression analysis revealed a significant negative correlation between malnutrition and SCL (β coefficient = - 0.129, p = 0.012) and negative associations among body mass index (β coefficient = - 0.010, p = 0.041), ferritin (β coefficient = - 0.107, p = 0.001) and SCL. A multivariate logistic regression analysis also demonstrated a negative correlation between malnutrition and SCL. With a 10-fold increase in SCL, the risk ratio of malnutrition was 0.49 (95% confidence interval: 0.25-0.96; p = 0.039)., Conclusions: SCL is significantly associated with malnutrition in MHD patients. Further evaluation of the relationship between clinical outcomes (morbidity/mortality) and SCL is necessitated.

Background: Malnutrition is frequent among vascular surgery patients, given their age, chronic comorbidities, and poor functional status, and it is believed to increase their operative risk. We aimed to assess the combined use of recent significant weight loss (>10% body mass) and serum albumin levels as a nutritional status index to predict outcomes., Methods: We analyzed vascular surgery data from the American College of Surgeons National Surgical Quality Improvement Program database (2005-2012; N = 238,082) to compare operative death (in-hospital and 30-day operative death) across eight nutritional status groups based on weight loss (yes/no) and albumin category: very low albumin level (VL-Alb; <2.50 g/dL), low albumin level (L-Alb; 2.50-3.39 g/dL), normal albumin level (N-Alb; 3.40-4.39 g/dL), and high albumin level (H-Alb; 4.40-5.40 g/dL). Risk-adjusted odds ratios (AOR) with 95% confidence intervals were estimated by multivariable logistic regression (N-Alb [no weight loss], reference)., Results: The study population included 113,936 patients for whom albumin level was available (age, 67 ± 13 years; 60.2% male). Operative death was documented in 5160 (4.53%) patients. The eight-category nutritional status was more predictive of operative death than age alone (C statistic, 0.74 vs 0.63). A high discrimination multivariable model for operative death was derived (C statistic, 0.851). Low albumin level was associated with increased death that worsened in case of weight loss: VL-Alb + WL, AOR = 3.83 (3.03-4.83); VL-Alb, AOR = 3.36 (3.06-3.69); L-Alb + WL, AOR = 2.46 (1.98-3.05); and L-Alb, AOR = 1.99 (1.84-2.15). Weight loss was associated with increased death even if albumin level was normal: N-Alb + WL, AOR = 1.77 (1.34-2.35); and H-Alb + WL, AOR = 1.91 (0.69-5.31). H-Alb was protective (AOR = 0.65 [0.55-0.76])., Conclusions: Nutritional status predicts outcomes of vascular surgery. Serum albumin level and weight loss should be incorporated in patients' risk stratification., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT)., Materials and Methods: A total of 286 patients with stage II-IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm 3 at diagnosis, and treatment-related lymphopenia was defined as total lymphocyte count <200 cells per mm 3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment-related lymphopenia and treatment response., Results: Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m 2 , and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment-related lymphopenia. Tumor progression and cancer-related death were more frequently observed in treatment-related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment-related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia., Conclusion: Treatment-related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC., Implications for Practice: A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment-related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment-related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: The Bedouins living in southern Israel are a Muslim-Arab population that is transitioning from a nomadic lifestyle to life in permanent settlements. The population has unique characteristics that could affect hemoglobin A1c (HbA1c) measurements. The objective of this study was to describe the socio-demographic and unique morbidity characteristics of this community and their effect on HbA1c measurements. Consanguinity, especially among cousins in the Bedouin population, results in a high prevalence of autosomal recessive genetic diseases such as thalassemia (underestimate of HbA1c), hemoglobinopathies (underestimate and overestimate), Gilbert's disease, and glucose-6-phosphate dehydrogenase deficiency, an X-linked disorder, which can cause hyperbilirubinemia with an overestimate of HbA1c. Furthermore, nutritional deficiencies, autosomal recessive diseases, high birth rates, parasitic infections, and poverty can all cause high rates of anemia (iron and vitamin B12 deficiencies) that can raise HbA1c levels. Congenital dyserythropoietic anemia is found among Bedouin tribes in the Negev region and can lead to an underestimation of HbA1c levels. Pregnancy can also affect HbA1c levels. Medical teams working in the Bedouin community and in other Muslim populations with similar morbidity characteristics throughout the world should identify patients with medical conditions that can affect HbA1c measurements and be aware of possible measurement alternatives such as fructosamine and glycated albumin.

Background: Reliable and valid tools to screen for malnutrition in the intensive care unit (ICU) remain elusive. The sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100], could be an inexpensive, objective tool to predict malnutrition. We evaluated the SI as a screening tool for malnutrition in the ICU and compared it with the modified-NUTRIC score., Materials and Methods: This was a historical cohort study of ICU patients with stable kidney function admitted to Mayo Clinic ICUs between 2008 and 2015. Malnutrition was defined by the Subjective Global Assessment. Diagnostic performance was evaluated with the area under the receiver operating characteristic curve (AUC) and multivariable logistic regression., Results: Of the 398 included patients, 181 (45%) had malnutrition, with 34 (9%) scored as severely malnourished. The SI was significantly lower in malnourished patients than in well-nourished patients (64 ± 27 vs 72 ± 25; P = 0.002), and reductions in SI corresponded to increased malnutrition severity (P = 0.001). As a screening tool, the SI was an indicator of malnutrition risk (AUC 0.61) and performed slightly better than the more complex modified-NUTRIC score (AUC = 0.57). SI cutoffs of 101 and 43 had >90% sensitivity and >90% specificity, respectively, for the prediction of malnutrition. Patients with a low SI (≤43) had a significantly higher risk of mortality (HR = 2.61, 95% CI 1.06-6.48, P = 0.038)., Conclusion: The frequency of malnutrition was high in this critically ill population, and it was associated with a poor prognosis. The SI could be used to assess nutrition risk in ICU patients., (© 2018 American Society for Parenteral and Enteral Nutrition.)

This experiment evaluated the effects of subnutrition during early gestation on hematology in cows (Bos Taurus) and on hematological, metabolic, endocrine, and vitality parameters in their calves. Parda de Montaña and Pirenaica dams were inseminated and assigned to either a control (CONTROL, 100% requirements) or a nutrient-restricted group (SUBNUT, 65%) during the first third of gestation. Dam blood samples were collected on days 20 and 253 of gestation, and calf samples were obtained during the first days of life. Pirenaica dams presented higher red series parameters than Parda de Montaña dams, both in the first and the last months of gestation. During early pregnancy, granulocyte numbers and mean corpuscular hemoglobin were lower in Pirenaica-SUBNUT than in Pirenaica-CONTROL cows. Calves from the SUBNUT cows did not show a physiological reduction in red series values in early life, suggesting later maturation of the hematopoietic system. Poor maternal nutrition affected calf endocrine parameters. Newborns from dystocic parturitions showed lower NEFA concentrations and weaker vitality responses. In conclusion, maternal nutrition had short-term effects on cow hematology, Pirenaica cows showing a higher susceptibility to undernutrition; and a long-term effect on their offspring endocrinology, SUBNUT newborns showing lower levels of IGF-1 and higher levels of cortisol., (© 2019 Japanese Society of Animal Science.)

Background: The aim of the study was to investigate the serum concentration of cytokines and biochemical markers of malnutrition in correlation with frailty syndrome in patients qualified for lung transplantation (LTx)., Methods: The study population comprised 31 potential lung recipients, including 18 patients with idiopathic lung disease, 12 patients with chronic obstructive pulmonary disease, and 1 patient with bronchiectasis who qualified for a LTx. Cytokine serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits and the Luminex 200 platform (ProcartaPlex Hu Cytokine/Chemokine Panel 1A 34plex, Invitrogen, Carlsbad, Calif., United States). The patients were also asked to complete a questionnaire, the Clinical Frailty Scale., Results: All patients were found to have higher cytokine concentrations (IL6, IL 2,IL18, IL23, IL 12p70, IL 10, IL 7). No statistically significant differences in the analyzed cytokines were noted when the men's results were compared to those of the women. There were no significant differences between patients who scored 6 vs 7 points on the Canadian Study of Health and Aging Function Scale. In comparing chronic obstructive pulmonary disease to idiopathic lung disease patients, no significant differences were observed in the analyzed cytokine values. Significant correlations were observed between the analyzed cytokines and age of the patients, C-reactive protein, triglycerides, transferrin, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol., Conclusions: Our findings indicate that cytokines may not have a statistically significant effect on the parameters of the frailty syndrome. The results require further investigations on larger study groups. The findings suggest that the analyzed cytokines may play a proinflammatory role in the end stages of lung diseases, but further studies are needed to evaluate whether these cytokines could be used as biomarkers in this group of patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of early-life exposure to the Chinese Great Famine (1959-1961) with DNA methylation in IGF2 and its subsequent influence on blood lipid levels in late adulthood among participants of the Genomic Research of the Chinese Famine (GRECF) study., Methods: The GRECF study recruited 790 participants born between 1956 and 1964 from 2 neighbor provinces, Anhui and Jiangxi, in China through a multistage, clustered, random sampling. The current study included a random sample of 188 GRECF participants. IGF2 differential methylation region (DMR) is an intragenic DMR located upstream of the imprinted promoters of IGF2 exon 3. DNA methylation were quantified at 8 cytosine-phosphate-guanine dinucleotides (CpG) sites at the IGF2 DMR (chr11p15.5) using the Sequenom EpiTYPER method and the MassARRAY system. Multivariate linear regressions were used to evaluate pairwise associations among famine severity, DNA methylation in the IGF2 gene, and lipid levels. We controlled for age and sex in the base model and additionally controlled for education, smoking, and drinking status in the fully adjusted model. Mediation analysis was applied to assess the mediation effect of DNA methylation at the IGF2 gene on the association between early-life exposure to severe famine and adult lipid levels., Results: Exposure to severe famine was associated with elevated methylation at CpG1 (chr11: 2126041, build 36) of the IGF2 DMR (β = 0.07; P = 0.0008) and total cholesterol (β = 0.72; P = 1.09 × 10 -7 ). After adjustment for age and sex, each unit increase in methylation of the CpG1 site was associated with 1.09-unit increase in total cholesterol (P = 0.03). After further adjustment for all covariates, these associations were still significant (P famine-CpG1  = 0.002, P famine-total cholesterol  = 1.28 × 10 -6 , and P CpG1-total cholesterol  = 0.05)., Conclusion: Increased methylation level in the IGF2 gene was associated with early-life exposure to severe famine, and this change was also positively associated with total cholesterol in late adulthood.

Aims: Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this interindividual variability., Methods: From December 2014 to November 2015, 183 patients were prospectively included. Serum CDA activity, biological and clinical characteristics as well as five common single nucleotide polymorphisms (SNPs) in the CDA gene (c.-451C > T, c.-92A > G, c.-33&#95;-31delC, c.79A > C, c.435 T > C) were analysed. Associations between clinical characteristics, pharmacogenetic variants and CDA activity were univariately tested. P < 0.1-candidate variables were analysed through a multivariate analysis. The association between CDA activity and toxicity was assessed for the 56 gemcitabine-treated patients. Intraindividual variability in CDA activity was explored in six pancreatic cancer patients treated with gemcitabine., Results: Median CDA activity was 3.97 U mg -1 (range 1.53-15.49 U mg -1 ). A univariate analysis showed that CDA activity was statistically associated with Eastern Cooperative Oncology Group performance status, mild or severe malnutrition, inflammatory syndrome, leucocyte count, neutrophil count, albumin, C-reactive protein and -c.-33&#95;-31delC single nucleotide polymorphism. A multivariate analysis identified that only neutrophil count (P < 0.0001) and severe malnutrition (P = 0.0278) were independently associated with CDA activity. Low CDA activity (<2 U mg -1 ) was not statistically associated with severe gemcitabine-related toxicities (P = 0.16). A decrease in CDA activity was observed during the longitudinal follow-up of six pancreatic cancer patients treated with gemcitabine (P = 0.03)., Conclusions: These results suggest that neutrophil count and malnutrition should be considered for the interpretation of pretherapeutic CDA activity., (© 2018 The British Pharmacological Society.)

Preoperative risk stratification has long been developed as a strategy to predict postoperative outcomes and potentially alter or optimize comorbidities and modifiable risk. Malnutrition is among the most common potentially modifiable risk factors and the strongest predictor of poor postsurgical outcomes. Historically, malnutrition has been difficult to address for healthcare providers because of the lack of a cohesive definition. Adding to the confusion has been the use of serum levels of albumin and prealbumin as biomarkers for malnutrition; many fail to understand that these visceral proteins are only valid as markers of nutrition status while at homeostasis. Surgical need is often driven by both sterile and non-sterile inflammation, but during this pathologic mechanism, hepatic reprioritization shunts visceral protein synthesis, rendering albumin and prealbumin invalid as biomarkers for malnutrition. Ultimately, understanding these limitations and embracing better indicators of malnutrition will improve preoperative risk stratification., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Introduction: Pre-eclampsia is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Although subclinical hypothyroidism (SCH) in pregnancy is one of the established risk factors for pre-eclampsia, the link between iodine deficiency, the main cause of hypothyroidism and pre-eclampsia remains uncertain. About two billion people live in areas with iodine insufficiency. The increased renal blood flow during pregnancy leading to increased renal iodine clearance together with the increased placental transfer of iodine to the fetus leads to further iodine deficiency in pregnancy. Iodine is one of the most potent exogenous antioxidants whose deficiency is associated with oxidant imbalance and endothelial dysfunction, one of the mechanisms associated with increased risk of pre-eclampsia., Methods and Analysis: A systematic search of published literature will be conducted for case-control studies that directly determined the iodine nutrition status of women with pre-eclampsia and appropriate normotensive controls. A similar search will be conducted for cohort studies in which the incidence of pre-eclampsia among pregnant women with adequate and inadequate iodine nutrition status was reported. Databases including MEDLINE, EMBASE, Google Scholar, SCOPUS and Africa Wide Information will be searched up to 31 December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias of the included studies will be assessed using a Newcastle-Ottawa Scale. Appropriate meta-analytic techniques will be used to pool prevalence and incidence rates, odds and relative risk of pre-eclampsia from studies with similar features, overall and by geographical regions. Heterogeneity of the estimates across studies will be assessed and quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines., Ethics and Dissemination: Since the proposed study will use published data, there is no requirement for ethical approval. This review seeks to identify the risk of pre-eclampsia associated with insufficient iodine nutrition in pregnancy. This will help to ascertain whether insufficient iodine intake may be an independent risk factor for pre-eclampsia. This will advise policy makers on the possibility of maximising iodine nutrition in pregnancy and reproductive age as one of the remedies for prevention of pre-eclampsia among populations at risk of inadequate iodine intake. This review is part of the thesis that will be submitted for the award of a PhD in Medicine to the Faculty of Health Sciences of the University of Cape Town. In addition the results will be published in a peer-reviewed journal., Prospero Registration Number: CRD42018099427., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: PS is partly supported by a project grant from MRC (Grant Ref: MR/J000094/1) which is designed to assess the impact of B12 levels in early pregnancy on gestational diabetes.

Background: Malnutrition continues to be prevalent in the general population. A variety of studies have correlated poor nutritional status with reduced perioperative outcomes. However, the correlation between serologic malnutrition and arthroplasty outcomes has not been systematically evaluated. The purpose of this study was to determine if serologic malnutrition has a correlation with postoperative wound infection, as well as other complications, after total joint arthroplasty., Methods: A systematic review of the literature was performed to identify studies that reported on outcomes for patients who were malnourished and had undergone a total hip or knee arthroplasty., Results: Twenty studies were included for review. Based on the quality of the evidence of the different studies, the balance between desirable/undesirable outcomes and the values of patients, there was a strong recommendation that preoperative serologic markers of malnutrition are significantly associated with inferior postoperative outcomes. All 20 studies analyzed albumin as a marker for malnutrition. Eleven (55%) studies used the total lymphocyte count, and 6 (30%) studies reported transferrin as a marker for malnutrition. Among 20 studies, 18 (90%) studies reported a correlation with at least one serological marker and poor postoperative outcomes. Finally, patients with an albumin level <3.5 dg/L were more likely to develop a postoperative wound complication (odds ratio: 2.176; 95% confidence interval: 1.916-2.471)., Conclusions: There is strong evidence that serologic malnutrition was associated with increased risk of poor postoperative outcome across all total joint replacement interventions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Malnutrition has been associated with adverse postoperative outcomes in a range of procedures but none have evaluated the interaction between clinical indicators of malnutrition. We aimed to comparatively evaluate how combinations of nutritional parameters impact postoperative outcomes amongst patients undergoing major cancer operations., Methods: Major abdominopelvic cancer surgery cases (colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, nephrectomy, pancreatectomy, pneumonectomy and prostatectomy) were identified in the American College of Surgeons National Surgical Quality Improvement Program database from 2007-2016. Malnutrition was defined by the presence of the following parameters: body mass index <18.5 kg/m 2 ; preoperative serum albumin <3.0 g/dL or more than 10% weight loss in the last 6 months. Malnourished cases were matched with cases with satisfactory nutritional status using propensity scores. The primary outcome was the incidence of Clavien III-IV complications., Results: Of the 30 207 cases included, 8.5% had at least one marker of malnutrition. The incidence of Clavien III-IV complications across all cases was 5.8%. In the matched cohort, malnourished cases had a higher rate of complications than those with adequate nutritional status (11.3% versus 9.6%, P = 0.018). A correlation was observed between the number of malnutrition markers possessed and the incidence of Clavien III-V complications. Cases with all three makers had the highest likelihood of experiencing a complication (odds ratio 5.47, 95% confidence interval 1.85-16.17)., Conclusion: Poor nutritional status confers an increased risk of major postoperative complications and being discharged to a facility in non-upper gastrointestinal cancer patients. There was a correlation between the number of malnutrition parameters and the risk of complications., (© 2019 Royal Australasian College of Surgeons.)

We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites., Competing Interests: The authors declare no conflict of interest.

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.)

Multiple studies on the dynamics of inflammatory cytokines in patients with anorexia nervosa (AN) have been published, although results are not consistent among reports. Thus the pathophysiologic roles of these cytokines are not clear. We performed an exploratory analysis that included (1) comparisons of plasma interleukin-18 (IL-18) concentrations between patients with AN ( n = 21) and healthy controls ( n = 39), and (2) correlations between body mass index (BMI) and IL-18 concentrations in both groups, exploring the relationship between malnourishment and IL-18. Plasma IL-18 levels were significantly decreased in patients with AN compared with controls. Plasma IL-18 levels correlated to BMI in controls, but not in patients with AN. These results suggest that a decline in plasma IL-18 levels in patients with AN is not only due to malnourishment, but other pathophysiologic changes as well. IL-18 has a role in the brain's reaction to sadness and chronic stress. Therefore, decreased levels of IL-18 may commonly occur in patients with chronic AN.

Objective: To examine the relationship of nutrition parameters with the modified frailty index (mFI) and postoperative complications in hip fracture patients., Design: Retrospective observational cohort study., Setting: Urban, American College of Surgeons-Verified, Level-1, Trauma Center., Patients/participants: Three hundred seventy-seven consecutive patients with isolated hip fractures., Intervention: N/A., Main Outcome Measures: On admission, albumin and total lymphocyte count (TLC) levels and complication data were collected. Additionally, mFI scores were calculated. Statistical analysis was then used to analyze the association between frailty, malnutrition, and postoperative complications., Results: Overall, 62.6% and 17.5% of patients were malnourished as defined by TLC of <1500 cells per cubic millimeter and albumin of <3.5 g/dL, respectively. Both TLC (P = 0.024; r = -0.12) and albumin (P < 0.001; r = -0.23) weakly correlated with frailty. Combining malnutrition and frailty revealed predictive synergy. Albumin of <3.5 g/dL and mFI of ≥0.18 in the same patient resulted in a positive predictive value of 69% and a likelihood ratio of 4 (2.15-7.43) for postoperative complications. Similarly, the combination of hypoalbuminemia and frailty resulted in a positive predictive value of 23.3% and likelihood ratio of 8.52 (P < 0.001) for mortality., Conclusions: When patients are frail and malnourished, there is a risk elevation beyond that of frailty or malnutrition in isolation. This high-risk cohort can be easily identified at admission with routine laboratory values and clinical history. There is an opportunity to improve outcomes in frail hip fracture patients because malnutrition represents a potentially modifiable risk factor., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Introduction: Malnutrition is a leading cause of morbidity and mortality in cirrhosis. Although multiple noninvasive measures of nutritional status have been studied, no consensus exists for early identification of malnutrition in cirrhosis. Serum metabolomics offers a novel approach for identifying biomarkers in multiple disease states. To characterize alterations in metabolic pathways associated with malnutrition in hospitalized cirrhotic patients and to identify biomarkers for disease prognosis., Methods: In this cross-sectional, observational cohort study, 51 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on low mid-arm muscle circumference and dominant handgrip strength. Anthropometric measurements and computed tomography body composition analysis were performed. Serum was collected after overnight fasting for unbiased metabolomics analysis., Results: Malnourished cirrhotic patients exhibited mild reductions in skeletal muscle index, with more marked reductions in visceral fat index. Seventy-one biochemicals were significantly altered in malnourished subjects. The serum metabolite profile was significantly different between nourished and malnourished cirrhotic patients. Pathway analysis demonstrated that only sphingolipid metabolic pathways were significantly enriched in altered metabolites. Hierarchical clustering revealed that sphingolipid metabolites clustered into nourished and malnourished cohorts. Spearman analysis demonstrated multiple statistically significant correlations between sphingolipid species and Model for End-Stage Liver Disease-Sodium. Using logistic regression, we identified 8 sphingolipids that were significantly associated with malnutrition after controlling for Model for End-Stage Liver Disease-Sodium, age, and gender., Conclusions: Malnutrition in hospitalized cirrhotic patients is characterized by reductions in multiple sphingolipid species. Dysregulated sphingolipid metabolism may be involved in the pathophysiology of malnutrition in cirrhosis and potentially serve as a biomarker of nutritional status in this population.

Background/aim: Fetuin-A, a circulating inhibitor of calcification, is a marker of inflammatory-nutritional state. We evaluated the association between serum fetuin-A levels and vascular calcification, intima-media thickness, and nutritional and inflammatory markers in different stages of chronic kidney disease (CKD)., Materials and Methods: CKD patients were sampled for calcium-phosphate parameters and nutritional and inflammatory markers [highly sensitive C-reactive protein (hs-CRP)], and serum fetuin-A levels. Intima-media thicknesses of the common carotid arteries (CIMT) were measured. Peripheral artery calcification scores were obtained., Results: A total of 238 patients were included in the study. Fetuin-A levels in patients with end-stage renal disease were significantly lower than those in patients with stage-3 and stage-4 CKD (stage-5 vs. stage-4, P < 0.001; stage-5 vs. stage-3, P < 0.001). Fetuin-A was negatively correlated with creatinine (P < 0.001), Ca × P product (P < 0.001), hs-CRP (P = 0.01), vascular calcification score (P < 0.001), and CIMT (P < 0.001), and positively correlated with BMI (P < 0.001, r = 0.30) and serum albumin (P < 0.001)., Conclusion: Lower levels of fetuin-A were associated with higher vascular calcification scores, CIMT, hs-CRP levels, and lower BMI and albumin. Fetuin-A deficiency may be a key element for MIAC syndrome.

Background: Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis (CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency (PEI), which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results., Aim: To investigate serum zinc levels in patients with CP of various etiologies., Methods: Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the M-ANNHEIM classification system into the following etiological subcategories: alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal (fecal elastase 1 > 200 μg/g), mildly reduced (100-200 μg/g) and severely reduced (fecal elastase 1 < 100 μg/g)., Results: A total of 150 patients were included in the analysis. Zinc deficiency (< 11 μmol/L) was present in 39 (26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency (FE-1 < 200 μg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI (1.08-13.4); P = 0.04]; [OR 6.26, 95%CI (1.94-20.2), P > 0.002]. Smoking and number of pack-years were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked. Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin (HbA1c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels., Conclusion: Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.

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.)

Objective: Neoplastic disease is frequently associated with poor nutritional status or severe malnutrition. Diet and nutritional intervention are becoming increasingly important for prognosis and quality of life in cancer patients. Accessible and repeatable tools for assessing nutritional status with body composition techniques seems to be fundamental. The aim of this study was to evaluate the effects of immunonutrition on body composition parameters, inflammatory response and nutritional status in patients at stage III of head and neck squamous carcinoma (HNSCC)., Patients and Methods: In our work, 50 malnourished subjects with HNSCC staging III were recruited and treated with oral diet (OD) or enteral nutrition (EN). Patient under EN followed, for the first three days, enteral standard nutrition (ESN) and then enteral immunonutrition (EIN). Nutrition state was evaluated on days 0, 3, and 8 through body composition and biochemical analyses., Results: After 8 days, the EIN treatment showed a significant improvement in phase angle, pre-albumin, retinol binding protein and transferrin compared to the OD treatment., Conclusions: Our results showed that immunonutrition treatment improves the nutritional status of neoplastic patients, supporting chemotherapy. The phase angle is not only a predictor of cancer survival, but has also proved to be useful in the surveillance of nutritional status improvement as well as biochemical indices.

Introduction: Malnutrition is a potentially modifiable risk factor associated with increased hospital charges, major wound complication, and fracture non-union after orthopaedic surgery. The goal of this study was to examine the relationship between three nutrition screening tools and postoperative complications in patients undergoing acute fracture fixation., Methods: Patients aged 18 or older undergoing acute operative fracture fixation at a Level I academic trauma center were screened upon admission using a malnutrition screening questionnaire (MSQ), and classified as low-, moderate- or high risk. Patients at moderate-to-high risk were assessed for clinical malnutrition by dietitian. Serum albumin, transferrin, total lymphocyte count, and 25(OH) Vitamin D were measured preoperatively. Primary outcome measures included twelve-month postoperative surgical and medical complications obtained by retrospective chart review., Results: Of 373 patients, 17% were moderate-to-high risk of malnutrition by MSQ. Clinical malnutrition was diagnosed by dietitian in 4.3% of patients assessed. Nearly half of all subjects had deficiency in one or more serum biomarkers. Cost of biomarker assays was $624 per patient. Medical or surgical complications occurred in 19% of patients. Dietitian diagnosed malnutrition (clinical malnutrition) was the strongest predictor of complication (OR 3.49, p = 0.017). Hypoalbuminemia was also associated with increased complication risk (OR 1.79, p = 0.045). MSQ score was not correlated with postoperative complication., Conclusions: Among the examined malnutrition screening tools, clinical malnutrition had the strongest association with postoperative complication. Hypoalbuminemia was associated with increased odds of complication, however there was a large false positive rate with all tested serum chemistries and high associated hospital charges compared to dietitian assessment. MSQ was a poor predictor of malnutrition and clinical outcome. Dietetic assessment is advised for orthopaedic trauma patients., (Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. 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: Zinc is an essential nutrient for all forms of life and its deficiency affects the normal growth and development of human beings., Objective: The main aim was to investigate zinc nutritional status by serum zinc concentration (SZC) and dietary zinc intake and their association in cystic fibrosis (CF) patients., Methods: A cross-sectional study was conducted in CF patients. Anthropometric measurements and respiratory and pancreatic tests were conducted. Hypozincemia was determined by SZC while using atomic absorption spectrophotometry and dietary zinc deficiency by prospective 72-h dietary surveys., Results: Mean SZC (87.2 ± 16.7 μg/dL) and dietary zinc intake (97 ± 26.9% Dietary Reference Intake) were normal. Three of 17 patients with CF (17.6%) had hypozincemia and four (23.5%) had a dietary zinc deficiency. No patient with dietary zinc deficiency had hypozincemia. A positive and significant association was observed between SZC and Z-score of BMI-for-age ( p = 0.048) and weight-for-height ( p = 0.012) and between dietary zinc intake and energy intake (EI, p = 0.036) and Z-score of weight-for-high ( p = 0.029)., Conclusion: SZC was associated with the nutritional status, expressed as BMI (Body Mass Index) and weight-for-height Z score, and dietary zinc intake with EI and weight-for-height Z-score. No patient with hypozincemia had dietary zinc deficiency. This situation should alert us to a marginal zinc deficiency and it may explain why there were no overlapping cases between the two groups. We suggest that probably 41% of the cases in this study would be at elevated risk of zinc deficiency and a zinc supplementation may be considered., Competing Interests: The authors declare no conflict of interest.

Background: Hypovitaminosis D is a frequent condition in elderly subjects. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D-25(OH)D-concentration in the serum. An inverse association exists between 25(OH)D and cardiovascular, infectious, glucose metabolism, cognitive disorders, and all-cause mortality. Whether 25(OH)D is a marker of organ diseases is still under debate. We aimed to investigate whether comorbidities were associated with serum 25(OH)D levels in geriatric inpatients., Methods: This is a retrospective study, including 237 subjects consecutively admitted to an acute care geriatric unit, with available data of 25(OH)D serum concentrations. 25(OH)D serum levels were defined according to the following cutoffs: 50⁻30 ng/mL (125⁻75 nmol/L): optimal range; 30⁻20 ng/mL (75⁻50 nmol/L): insufficiency; 20⁻10 ng/mL (5⁻25 nmol/L): deficiency; and <10 ng/mL (<25 nmol/L): severe deficiency. Comorbidity was assessed using the Cumulative Illness Rating Scale-Geriatric (CIRS-G). Two summary measures were obtained, the Illness Severity Index (CIRS-SI) and the Comorbidity Index (CIRS-CI)., Results: 177 (74.68%) women and 60 (25.32%) men with mean age of 85 ± 6 years old were enrolled. The majority of subjects (68.6%) were at risk of malnutrition. Overall, the burden of comorbidity was 1.87 ± 1.33 for CIRS-CI and 1.18 ± 0.40 for CIRS-SI. 25(OH)D serum concentrations were 10.58 ± 7.68 ng/mL, with 98.7% of subjects having vitamin D below 30 ng/mL and 56.6% with severe deficiency. An inverse correlation was found between 25(OH)D and both CIRS-SI ( r : -0.312; p < 0.0001) and CIRS-CI ( r : -0.306; p < 0.0001). Independent of multiple covariates an inverse association between both CIRS-SI ( p < 0.0001) and CIRS-CI ( p < 0.0001) and 25(OH)D was confirmed. Both CIRS-SI ( r = 0.251, p < 0.0001) and CIRS-CI ( r = 0.137, p = 0.016) were positively correlated with the length of hospital stay. An inverse correlation was confirmed between serum 25(OH)D concentrations and CRP ( r = -0.142; p = 0.041). CRP, in turn, positively correlated with CIRS-SI ( r = 0.209, p = 0.003) and CIRS-CI ( r = 0.158, p = 0.023). Both CIRS-SI ( r = 0.251, p < 0.0001) and CIRS-CI ( r = 0.137, p = 0.016) were positively correlated with the length of hospital stay., Conclusions: In hospitalized very old subjects, a higher comorbidity burden is associated with lower 25(OH)D serum levels. Hypovitaminosis D was correlated with higher inflammatory status, which, together with the comorbidities burden, negatively influenced the length of hospital stay., Competing Interests: The authors declare no conflict of interest.

Simplifying blood collection is often critical when collecting specimens in remote and/or austere settings. The use of dried blood spots (DBS) offers a practical collection method suitable for a wide variety of analytes. A small volume of whole blood can be obtained rapidly through a minimally invasive heel- or finger-stick using a disposable safety lancet. Once dried, the samples require no further processing, are stable for months or longer, pose minimal risk of disease transmission, and are easy to ship. DBS are often used in demographic health surveys to assess infectious disease status in vulnerable populations. These samples can be used to screen biomarkers of micronutrient deficiency (MND) and inflammation. We recently described a multiplexed immunoarray, the Q-plex human micronutrient array, which can simultaneously quantify seven biomarkers related to MND, inflammation and malarial antigenemia using plasma (alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein, soluble transferrin receptor, and thyroglobulin). In this work, we present a protocol for preparing eluates from DBS samples and their measurement using a modified protocol for this new tool. We evaluated the concordance of analyte concentrations (excluding ferritin) from a panel ninety samples of DBS prepared from anticoagulated venous blood and paired K2-EDTA plasma. The results show high correlation between DBS eluates and wet plasma for five of the six analytes screened, suggesting the Q-plex human micronutrient array can be used with DBS samples, but also highlighting that anticoagulants can have a negative effects on some test components., Competing Interests: CL is an employee of Quansys Biosciences, the manufacturer the of the 7-plex human micronutrient array that we describe in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No other authors have any competing interests with this work.

Background/aim: In maintenance hemodialysis (MHD), protein-energy malnutrition and chronic inflammation can be critical and are two of the main causes of mortality., Method: We compared the change in nutrition and inflammatory conditions between younger and older MHD patients during a 2-year period. Furthermore, using Kaplan-Meier analysis, we evaluated the correlations between changes in each parameter and any adverse events., Result: During the observational period, body mass index (BMI) and serum albumin levels decreased significantly in older patients. In Kaplan-Meier analysis, patients who showed a decline in BMI had an associated elevated risk for cerebro-cardiovascular disease and hospitalization. Moreover, patients who showed a decline in albumin also had an associated higher risk for infectious disease and hospitalization., Conclusion: This study revealed that the downward trend in nutritional status was prominent in elderly patients. Furthermore, changes in nutritional and inflammatory conditions during MHD were associated with adverse events in MHD patients., (© 2019 S. Karger AG, Basel.)

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.