Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM).

PURPOSE: Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS: In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION: The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).

[DGEM Guideline "Clinical Nutrition in Critical Care Medicine" - short version]. / DGEM-Leitlinie: Klinische Ernährung in der Intensivmedizin ­ Kurzversion.

PURPOSE: Variations of clinical nutrition may affect outcome of critically ill patients. Here we present the short version of the updated consenus-based guideline (S2k classification) "Clinical nutrition in critical care medicine" of the German Society for Nutritional Medicine (DGEM) in cooperation with 7 other national societies. The target population of the guideline was defined as critically ill adult patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g. mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. We considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of international societies. The liability of each recommendation was indicated using linguistic terms. Each recommendation was finally validated and consented by a Delphi process. RESULTS: The short version presents a summary of all 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in the target population. A specific focus is the adjustment of nutrition according to the phases of critical illness, and to the individual tolerance to exogenous substrates. Among others, recommendations include the assessment of nutritional status, the indication for clinical nutrition, the timing, route, magnitude and composition of nutrition (macro- and micronutrients) as well as distinctive aspects of nutrition therapy in obese critically ill patients and those with extracorporeal support devices. CONCLUSION: The current short version of the guideline provides a concise summary of the updated recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring pharmacological and/or mechanical support. The validity of the guideline is approximately fixed at five years (2018 - 2023).

Omega-3 Fatty acids and vitamin d in cardiology.

Dietary modification and supplementation play an increasingly important role in the conservative treatment of cardiovascular disease. Current interest has focused on n-3 polyunsaturated fatty acids (PUFA) and vitamin D. Clinical trial results on this subject are contradictory in many aspects. Several studies indicate that n-3 PUFA consumption improves vascular and cardiac hemodynamics, triglycerides, and possibly endothelial function, autonomic control, inflammation, thrombosis, and arrhythmia. Experimental studies show effects on membrane structure and associated functions, ion channel properties, genetic regulation, and production of anti-inflammatory mediators. Clinical trials evaluating a possible reduction in cardiovascular disease by n-3 PUFA have shown different results. Supplementation of vitamin D is common regarding prevention and treatment of osteoporosis. But vitamin D also seems to have several effects on the cardiovascular system. Vitamin D deficiency appears to be related to an increase in parathyroid hormone levels and can predispose to essential hypertension and left ventricular hypertrophy, increased insulin resistance, and eventually to atherosclerosis and adverse cardiovascular events. Randomized prospective clinical trials are needed to determine whether vitamin D and omega-3 FA supplementation therapy should be recommended as a routine therapy for primary or secondary prevention of cardiovascular disease.

Lung level of HMBG1 is elevated in response to advanced glycation end product-enriched food in vivo.

High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that can be actively released from the cell in certain conditions thereby mediating cytokine-like function. While nuclear HMGB1 modulates the transcriptional activity of cells, extracellular HMGB1 partially acts via binding to the receptor for advanced glycation end products (RAGE), which is highly expressed in lung tissue. Therefore, we studied the impact of food-derived advanced glycation end products (AGEs), the Maillard reaction products, on the lung expression of HMGB1. Feeding rats with AGE-rich diet, containing either bread crust or coffee beverage, resulted in an upregulation of HMGB1 mRNA and protein especially in those animals receiving bread crust diet. The expression of RAGE was not influenced. Moreover, we revealed a positive correlation between an increased lung AGE level and HMGB1 protein expression in both animal groups receiving either bread crust or coffee extract but not in the control group. In contrast, the ageing-related AGE accumulation was not associated with an increased level of HMGB1 protein in lung tissue from senescent (100 wk) compared to young-adult (24 wk) rats. Our data suggest a physiological role of food- but not ageing-associated AGEs in the regulation of the HMGB1 expression in lung.