The association between body-mass index and patient outcome in septic shock: a retrospective cohort study

Zusammenfassung: HINTERGRUND: Es bestehen keine Daten über die Assoziation zwischen dem Body Mass Index (BMI) bzw. BMI Kategorien und der Mortalität von septischen Schock-patienten. METHODEN: Die Datenbank einer interdisziplinären Intensivstation wurde retrospektiv nach erwachsenen Patienten mit septischem Schock durchsucht. Von allen Patienten wurde der BMI, demographische, klinische und laborchemische Parameter gemeinsam mit Outcomevariabeln dokumentiert. Die Studienpatienten wurden wie folgt anhand des BMI kategorisiert: BMI 30 kg/m2, Fettleibigkeit. Bivariate und multivariate logistische Regressionsmodelle wurden verwendet, um den Zusammenhang zwischen dem BMI und Outcome-variabeln zu untersuchen. RESULTATE: 301 septische Schockpatienten wurden identifiziert. Der BMI war bivariat mit der Mortalität auf der Intensivstation assoziiert (OR, 0,91; 95% CI, 0,86-0,98; p = 0,007). Es gab keine signifikante Assoziation zwischen dem BMI und der Mortalität auf der Intensivstation. Allerdings waren höhere BMI Werte trendmässig mit einer niedrigeren Intensivstations-mortalität assoziiert (OR, 0,93; 95% CI, 0,86-1,01; p = 0,09). Während übergewichtige (OR, 0,43; 95% CI, 0,19-0,98; p = 0,04) und fettleibige (OR, 0,28; 95% CI, 0,08-0,93; p = 0,04) Patienten ein unabhängig niedrigeres Risiko auf der Intensivstation zu versterben hatten als normalgewichtige Patienten, gab es keinen Unterschied im Sterberisiko zwischen normal- und untergewichtigen Patienten (p = 0,22). Ein hoher BMI war unabhängig mit einer geringen Häufigkeit eines akutem Deliriums (p = 0,04) und einer geringeren Intensivwieder-aufnahmerate (p = 0,001), aber mit mehr Harnwegsinfektionen (p = 0,02) assoziiert. SCHLUSSFOLGERUNG: Bis zu einem BMI von 50 kg/m2 scheint keine Assoziation zwischen BMI und schlechterem Überleben auf der Intensivstation oder im Krankenhaus bei septischen Schockpatienten zu bestehen. Im Gegenteil, hohe BMI Werte könnten sogar das Risiko am septischen Schock zu versterben reduziere

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study

It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock

A gut bacterial signature in blood and liver tissue characterizes cirrhosis and hepatocellular carcinoma

BackgroundHCC is the leading cause of cancer in chronic liver disease. A growing body of experimental mouse models supports the notion that gut-resident and liver-resident microbes control hepatic immune responses and, thereby, crucially contribute to liver tumorigenesis. However, a comprehensive characterization of the intestinal microbiome in fueling the transition from chronic liver disease to HCC in humans is currently missing.MethodsHere, we profiled the fecal, blood, and liver tissue microbiome of patients with HCC by 16S rRNA sequencing and compared profiles to nonmalignant cirrhotic and noncirrhotic NAFLD patients.ResultsWe report a distinct bacterial profile, defined from 16S rRNA gene sequences, with reduced α-and β-diversity in the feces of patients with HCC and cirrhosis compared to NAFLD. Patients with HCC and cirrhosis exhibited an increased proportion of fecal bacterial gene signatures in the blood and liver compared to NAFLD. Differential analysis of the relative abundance of bacterial genera identified an increased abundance of Ruminococcaceae and Bacteroidaceae in blood and liver tissue from both HCC and cirrhosis patients compared to NAFLD. Fecal samples from cirrhosis and HCC patients both showed a reduced abundance for several taxa, including short-chain fatty acid-producing genera, such as Blautia and Agathobacter. Using paired 16S rRNA and transcriptome sequencing, we identified a direct association between gut bacterial genus abundance and host transcriptome response within the liver tissue.ConclusionsOur study indicates perturbations of the intestinal and liver-resident microbiome as a critical determinant of patients with cirrhosis and HCC

Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD). Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC) also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC

Weight Loss Induced by Bariatric Surgery Restricts Hepatic GDF15 Expression

Introduction. Obesity and related nonalcoholic fatty liver disease (NAFLD) are an emerging health care issue that imposes substantial morbidity to individuals. Growth and differentiation factor 15 (GDF15) limits food uptake, body weight, and energy balance by modulation of GDNF-family receptor α-like (GFRAL) signalling in the hindbrain. However, the regulation of GDF15 expression in obesity and NAFLD is incompletely understood. We sought to define the impact of weight loss achieved by laparoscopic adjustable gastric banding (LAGB) on hepatic and adipose GDF15 expression in a cohort of severely obese patients. Methods. We analysed GDF15 expression of liver and subcutaneous adipose tissue before and 6 months after LAGB in severely obese patients undergoing LAGB by quantitative real-time PCR. To assess the role of inflammation on GDF15 expression, we analysed Hep G2 hepatocytes stimulated with cytokines such as IL-1β, TNFα, IL-6, LPS, or cellular stressors such as tunicamycin. Results. GDF15 expression was mostly confined to the liver compared to adipose tissue in severely obese patients. Weight loss induced by LAGB was associated with reduced hepatic (but not adipose tissue) expression of GDF15. Stimulation with IL-1β or tunicamycin induced hepatic GDF15 expression in hepatocytes. In line with this, hepatic GDF15 expression directly correlated with IL-1β expression and steatosis severity in NAFLD. These data demonstrated that amelioration of metabolic inflammation and weight loss reduced hepatic GDF15 expression. Conclusion. Based on recent mechanistic findings, our data suggest that hepatic GDF15 may serve as a negative feedback mechanism to control energy balance in NAFLD

Supervised Short-term High-intensity Training on Plasma Irisin Concentrations in Type 2 Diabetic Patients.

Irisin is a myokine involved in adipocyte transformation. Its main beneficial effects arise from increased energy expenditure. Irisin production is particularly stimulated by physical exercise. The present study investigates the changes of plasma irisin in type 2 diabetic patients performing 2 different training modalities. Fourteen type 2 diabetic patients underwent 4 week of supervised high-intensity interval training (HIT; n=8) or continuous moderate-intensity training (CMT; n=6), with equivalent total amounts of work required. Plasma samples were collected in the resting state atbaseline and one day after the exercise intervention to analyse resting plasma irisin, blood lipids, blood glucose, hsCRP, Adiponectin, Leptin and TNF-α concentrations. In addition, body composition and VO were determined Resting plasma irisin increased after HIT (p=0.049) and correlated significantly with plasma fasting glucose at follow-up (r=0.763; p=0.006). CMT did not significantly change the amount of plasma irisin, although follow-up values of plasma irisin correlated negatively with fat-free mass (r=-0.827, p=0.002) and with fasting plasma glucose (r = - 0.934, p=0.006). Plasma irisin was found to increase with higher training intensity, confirming the assumption that exercise intensity, in addition to the type of exercise, may play an important role in the stimulation of the irisin response

Association between nonalcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes - the Cooperative Health Research in South Tyrol (CHRIS)-NAFLD Substudy

Background and aims: Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD), both with and without type 2 diabetes mellitus (T2DM). Cardiac autonomic dysfunction is a risk factor for CVD morbidity and mortality. The aim of this pilot study was to assess whether there is an association between NAFLD and impaired cardiac autonomic function. Methods and results: Among the first 4979 participants from the Cooperative Health Research in South Tyrol (CHRIS) study, we randomly recruited 173 individuals with T2DM and 183 age- and sex-matched nondiabetic controls. Participants underwent ultrasonography and vibration-controlled transient elastography (Fibroscan®, Echosens) to assess hepatic steatosis and liver stiffness. The low-to-high-frequency (LF/HF) power ratio and other heart rate variability (HRV) measures were calculated from a 20-min resting electrocardiogram (ECG) to derive a measure of cardiac sympathetic/parasympathetic imbalance. Among the 356 individuals recruited for the study, 117 had NAFLD and T2DM, 56 had T2DM alone, 68 had NAFLD alone, and 115 subjects had neither condition. Individuals with T2DM and NAFLD (adjusted odds ratio [OR] 4.29, 95% confidence intervals [CI] 1.90–10.6) and individuals with NAFLD alone (adjusted OR 3.41, 95% CI 1.59–7.29), but not those with T2DM alone, had a substantially increased risk of having cardiac sympathetic/parasympathetic imbalance, compared with those without NAFLD and T2DM. Logistic regression models were adjusted for age, sex, body mass index (BMI), hypertension, dyslipidemia, insulin resistance, hemoglobin A1c (HbA1c), C-reactive protein (CRP), and Fibroscan®-measured liver stiffness. Conclusions: NAFLD was associated with cardiac sympathetic/parasympathetic imbalance, regardless of the presence or absence of T2DM, liver stiffness, and other potential confounding factors.</p

24-Norursodeoxycholic acid ameliorates experimental alcohol-related liver disease and activates hepatic PPARγ

Background &amp; Aims: Alcohol-related liver disease (ALD) is a global healthcare challenge with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a synthetic bile acid with anti-inflammatory properties in experimental and human cholestatic liver diseases. In the present study, we explored the efficacy of norUDCA in experimental ALD. Methods: NorUDCA was tested in a preventive and therapeutic setting in an experimental ALD model (Lieber–DeCarli diet enriched with ethanol). Liver disease was phenotypically evaluated using histology and biochemical methods, and anti-inflammatory properties and peroxisome proliferator-activated receptor gamma activation by norUDCA were evaluated in cellular model systems. Results: NorUDCA administration ameliorated ethanol-induced liver injury, reduced hepatocyte death, and reduced the expression of hepatic pro-inflammatory cytokines including tumour necrosis factor (Tnf), Il-1β, Il-6, and Il-10. NorUDCA shifted hepatic macrophages towards an anti-inflammatory M2 phenotype. Further, norUDCA administration altered the composition of the intestinal microbiota, specifically increasing the abundance of Roseburia, Enterobacteriaceae, and Clostridum spp. In a therapeutic model, norUDCA also ameliorated ethanol-induced liver injury. Moreover, norUDCA suppressed lipopolysaccharide-induced IL-6 expression in human peripheral blood mononuclear cells and evoked peroxisome proliferator-activated receptor gamma activation. Conclusions: NorUDCA ameliorated experimental ALD, protected against hepatic inflammation, and affected gut microbial commensalism. NorUDCA could serve as a novel therapeutic agent in the future management of patients with ALD. Impact and implications: Alcohol-related liver disease is a global healthcare concern with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a modified bile acid, which was proven to be effective in human cholestatic liver diseases. In the present study, we found a protective effect of norUDCA in experimental alcoholic liver disease. For patients with ALD, norUDCA could be a potential new treatment option

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study

Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection

Microbiota, type 2 diabetes and non-alcoholic fatty liver disease : protocol of an observational study

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. Methods: Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. Results: We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean - 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean - 1.30, SD, 1.17). Discussion: Given the comprehensive biochemical and clinical characterization of study participants, once the bio-informatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD