Fecal-adherent mucus is a non-invasive source of primary human MUC2 for structural and functional characterization in health and disease.

The O-glycoprotein Mucin-2 (MUC2) forms the protective colon mucus layer. While animal models have demonstrated the importance of Muc2, few studies have explored human MUC2 in similar depth. Recent studies have revealed that secreted MUC2 is bound to human feces. We hypothesized human fecal MUC2 (HF-MUC2) was accessible for purification and downstream structural and functional characterization. We tested this via histologic and quantitative imaging on human fecal sections; extraction from feces for proteomic and O-glycomic characterization; and functional studies via growth and metabolic assays in vitro. Quantitative imaging of solid fecal sections showed a continuous mucus layer of varying thickness along human fecal sections with barrier functions intact. Lectin profiling showed HF-MUC2 bound several lectins but was weak to absent for Ulex europaeus 1 (α1,2 fucose-binding) and Sambucus nigra agglutinin (α2,6 sialic acid-binding), and did not have obvious b1/b2 barrier layers. HF-MUC2 separated by electrophoresis showed high molecular weight glycoprotein bands (∼1-2 MDa). Proteomics and Western analysis confirmed the enrichment of MUC2 and potential MUC2-associated proteins in HF-MUC2 extracts. MUC2 O-glycomics revealed diverse fucosylation, moderate sialylation, and little sulfation versus porcine colonic MUC2 and murine fecal Muc2. O-glycans were functional and supported the growth of Bacteroides thetaiotaomicron (B. theta) and short-chain fatty acid (SCFA) production in vitro. MUC2 could be similarly analyzed from inflammatory bowel disease stools, which displayed an altered glycomic profile and differential growth and SCFA production by B. theta versus healthy samples. These studies describe a new non-invasive platform for human MUC2 characterization in health and disease.

Assessment of HBV variants and novel viral and immune biomarkers in chronic hepatitis B patients with metabolic dysfunction associated steatotic liver disease.

Co-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN-γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p < .01), higher HBV S diversity (p = .02) and greater frequency of HBV variants associated with host-anti-viral immune escape. Pro-inflammatory cytokine levels and HBV-specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low-level viraemia.

Experiences of Irritable Bowel Syndrome Patients in a Virtual Yoga Program: Qualitative Findings from a Clinical Trial.

BACKGROUND AND AIMS: In-person yoga interventions have shown feasibility and effectiveness in improving the outcomes of patients with irritable bowel syndrome (IBS), but experiences in virtual yoga interventions have not been examined. This study aimed to explore patients' experiences of a virtually delivered yoga intervention for IBS. METHODS: An embedded qualitative substudy was included in a randomized controlled trial examining the feasibility and effectiveness of a virtual yoga program among adult patients with IBS. Semi-structured interviews captured participants' past and current experiences, program satisfaction, perceived impact on IBS symptoms and overall physical and mental health, facilitators and barriers to participation, perceptions of social support and supervised learning, and input on improving future programming. Data were coded and analyzed in duplicate using NVivo 12. An analytic template based on the interview guide was developed and thematic analysis identified themes, as well as the relationship between themes and subthemes. RESULTS: Among the 14 participants (all female, mean age 47.7 years), three major themes were identified: (1) positive experience in the yoga program, (2) incorporating yoga into IBS management post-study, and (3) recommendations for program improvement. CONCLUSION: Patients with IBS experience in a virtual yoga program was positive with improvements in physical and mental health outcomes. Considering the barriers and facilitators to participating in an online yoga program along with participant recommendations may improve future intervention design and delivery to increase self-efficacy and confidence among patients with IBS.

Meditation and Yoga for Irritable Bowel Syndrome: A Randomized Clinical Trial.

INTRODUCTION: Delivered in person, yoga is effective in managing irritable bowel syndrome (IBS) symptoms. The evidence for efficacy, feasibility, and safety of virtually delivered yoga for patients with IBS is unknown. METHODS: Adults diagnosed with IBS were randomized to either Hatha yoga intervention of 8 weekly online classes delivered virtually or an advice-only control group and assessed at baseline and postintervention. We used an unadjusted ANOVA to determine differences between and within groups on the primary outcome (decrease of ≥50 points in IBS Symptom Severity Scale [IBS-SSS]) and secondary outcomes (quality of life, anxiety and depression, fatigue, somatic symptoms, perceived stress, COVID-19 stress, and self-compassion). We assessed feasibility through recruitment and attrition rates, adherence, participant satisfaction, and safety (i.e., adverse events). RESULTS: Seventy-nine people participated (mean age 45.4 years [SD = 14.0], 92% women, 20% attrition rate). IBS-SSS decreased significantly in the treatment group (Δ change = 54.7, P = 0.028), but not in the control group (Δ change = 22.6, P = 0.277). Fourteen patients (37%) in the yoga group reached a clinically relevant decrease of ≥50 points on the IBS-SSS postintervention compared with 8 patients (20%) in the control group ( P = 0.242). No significant difference was found between groups in IBS-SSS score postintervention ( P = 0.149), but significant differences in favor of the treatment group for quality of life ( P = 0.030), fatigue ( P = 0.035), and perceived stress ( P = 0.040) were identified. The yoga program demonstrated feasibility. Intention to practice yoga decreased significantly in both groups from baseline to postintervention ( P < 0.001). However, the decline in intention did not correlate with practice minutes. DISCUSSION: Virtually delivered yoga is safe and feasible, and effective in reducing IBS symptoms. Based on the primary end point, the intervention was not superior to an advice-only control group.

Effects of probiotics on bone mineral density and bone turnover: A systematic review.

Probiotic supplements have been shown to improve bone health in animal models, although it remains uncertain whether these beneficial effects extend to humans. We undertook a systematic review of the literature to determine the effects of probiotic interventions on skeletal outcomes in postmenopausal women. MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched from inception to October 2020 for controlled trials comparing the effects of probiotic-containing supplements with placebo on bone mineral density (BMD) or bone turnover markers. Risk of bias was assessed using the Cochrane Risk of Bias 2 Tool. Of 338 records identified, six randomized, placebo-controlled trials (n = 632) were eligible for inclusion. All studies assessed postmenopausal women for durations of 6-12 months; three were considered to be at high risk of bias. Four studies examined Lactobacillus-containing probiotics, one assessed a proprietary blend of lactic acid bacteria, and one evaluated Bacillus subtilis. Effects of probiotic interventions on BMD were inconsistent, with the majority of studies demonstrating no benefit at the spine or hip. Probiotic effects on bone turnover markers were similarly heterogeneous. High quality studies are needed to determine whether probiotic interventions have a role in maintaining bone health in humans.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis.

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: -1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561).

Using a Patient-Completed Food Frequency Questionnaire to Determine Mediterranean Diet Score in People with Inflammatory Bowel Disease.

Purpose: To examine the level of agreement between a patient-completed food frequency questionnaire (FFQ) and assessment of usual intake by a registered dietitian (RD) to score adherence to a Mediterranean diet (MedD) in patients with inflammatory bowel disease (IBD).Methods: Patients with IBD completed a short FFQ and were subsequently interviewed by an RD. A 12-item MedD score (MDS), adapted from the Mediterranean Diet Adherence Screener (MEDAS), was calculated from the FFQ and RD assessments. To determine agreement between individual items, Cohen's kappa coefficients were calculated. Absolute agreement between assessment methods was quantified using a one-way random intra-class correlation coefficient for a single measure.Results: Forty-six patients with IBD participated. The mean FFQ-MDS was 4.59 (standard deviation [SD] = 1.65), and mean RD-MDS was 4.83 (SD = 1.53). Kappa coefficients for individual MEDAS items ranged from 0.41 to 0.78 (p < 0.01) between the FFQ- and RD-MDS. Most items demonstrated moderate to substantial agreement. The intra-class correlation coefficient for absolute agreement between the summed FFQ-MDS and RD-MDS was 0.71 (95% confidence interval: 0.52-0.83, p < 0.001), indicating moderate reliability.Conclusions: This patient-completed FFQ may be a promising tool in clinical practice and research and would benefit from additional evaluation to validate its use in patients with IBD.

Predicted estimates of resting energy expenditure have limited clinical utility in patients with cirrhosis.

BACKGROUND & AIMS: Malnutrition is associated with adverse clinical outcomes in patients with cirrhosis. Accurate assessment of energy requirements is needed to optimize dietary intake. Resting energy expenditure (REE), the major component of total energy expenditure, can be measured using indirect calorimetry (mREE) or estimated using prediction equations (pREE). This study assessed the usefulness of predicted estimates of REE in this patient population. METHODS: Individual mREE data were available for 900 patients with cirrhosis (mean [±1 SD] age 55.7±11.6 years-old; 70% men; 52% south-east Asian) and 282 healthy controls (mean age 36.0±12.8 years-old; 52% men; 18% south-east Asian). Metabolic status was classified using thresholds based on the mean ± 1 SD of the mREE in the healthy controls. Comparisons were made between mREE and pREE estimates obtained using the Harris-Benedict, Mifflin, Schofield and Henry equations. Stepwise regression was used to build 3 new prediction models which included sex, ethnicity, body composition measures, and model for end-stage liver disease scores. RESULTS: The mean mREE was significantly higher in patients than controls when referenced to dry body weight (22.4±3.8 cf. 20.8±2.6 kcal/kg/24 hr; p <0.001); there were no significant sex differences. The mean mREE was significantly higher in Caucasian than Asian patients (23.1±4.4 cf. 21.7±2.9 kcal/kg/24 hr; p <0.001). Overall, 37.1% of Caucasian and 25.3% of Asian patients were classified as hypermetabolic. The differences between mREE and pREE were both statistically and clinically relevant; in the total patient population, pREE estimates ranged from 501 kcal/24 hr less to 548 kcal/24 hr more than the mREE. Newly derived prediction equations provided better estimates of mREE but still had limited clinical utility. CONCLUSIONS: Prediction equations do not provide useful estimates of REE in patients with cirrhosis. REE should be directly measured. LAY SUMMARY: People with cirrhosis are often malnourished and this has a detrimental effect on outcome. Provision of an adequate diet is very important and is best achieved by measuring daily energy requirements and adjusting dietary intake accordingly. Prediction equations, which use information on age, sex, weight, and height can be used to estimate energy requirements; however, the results they provide are not accurate enough for clinical use, particularly as they vary according to sex and ethnicity.

Prevalence and Risk Factors for Fatigue in Adults With Inflammatory Bowel Disease: A Systematic Review With Meta-Analysis.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disease with high morbidity, substantial health care costs, and increasing incidence. Fatigue is one of the most common symptoms that impacts quality of life and is a leading concern for patients with IBD. The aim of this study was to determine the global prevalence, risk factors, and impact of fatigue in adults with IBD. METHODS: A systematic review and meta-analysis was conducted. Data were retrieved from Medline, Embase, CINAHL, and PsycINFO from database inception to October 2019. A pooled prevalence of fatigue was calculated using a random-effects model. Stratified meta-analyses explored sources of between-study heterogeneity. Study quality was assessed using an adapted checklist from Downs and Black. RESULTS: The search yielded 4524 studies, of which 20 studies were included in the systematic review and meta-analysis. Overall, the studies were of good quality. The pooled prevalence of fatigue was 47% (95% confidence interval, 41%-54%), though between-study heterogeneity was high (I2 = 98%). Fatigue prevalence varied significantly by the definition of fatigue (chronic: 28%; high: 48%; P < .01) and disease status (active disease: 72%; remission: 47%; P < .01). Sleep disturbance, anxiety, depression, and anemia were the most commonly reported fatigue-related risk factors. CONCLUSIONS: The prevalence of fatigue in adults with IBD is high, emphasizing the importance of additional efforts to manage fatigue to improve the care and quality of life for patients with IBD.

Epidemiologic Burden and Treatment of Chronic Symptomatic Functional Bowel Disorders in the United States: A Nationwide Analysis.

BACKGROUND & AIMS: Functional bowel disorders (FBDs) are the most common gastrointestinal problems managed by physicians. We aimed to assess the burden of chronic symptomatic FBDs on ambulatory care delivery in the United States and evaluate patterns of treatment. METHODS: Data from the National Ambulatory Medical Care Survey were used to estimate annual rates and associated costs of ambulatory visits for symptomatic irritable bowel syndrome, chronic functional abdominal pain, constipation, or diarrhea. The weighted proportion of visits associated with pharmacologic and nonpharmacologic (stress/mental health, exercise, diet counseling) interventions were calculated, and predictors of treatment strategy were evaluated in multivariable multinomial logistic regression. RESULTS: From 2007-2015, approximately 36.9 million (95% CI, 31.4-42.4) weighted visits in patients of non-federally employed physicians for chronic symptomatic FBDs were sampled. There was an annual weighted average of 2.7 million (95% CI, 2.3-3.2) visits for symptomatic irritable bowel syndrome/chronic abdominal pain, 1.0 million (95% CI, 0.8-1.2) visits for chronic constipation, and 0.7 million (95% CI, 0.5-0.8) visits for chronic diarrhea. Pharmacologic therapies were prescribed in 49.7% (95% CI, 44.7-54.8) of visits compared to nonpharmacologic interventions in 19.8% (95% CI, 16.0-24.2) of visits (P < .001). Combination treatment strategies were more likely to be implemented by primary care physicians and in patients with depression or obesity. The direct annual cost of ambulatory clinic visits alone for chronic symptomatic FBDs is approximately US$358 million (95% CI, 233-482 million). CONCLUSIONS: The management of chronic symptomatic FBDs is associated with considerable health care resource use and cost. There may be an opportunity to improve comprehensive FBD management because fewer than 1 in 5 ambulatory visits include nonpharmacologic treatment strategies.

Diet in Treatment of Inflammatory Bowel Diseases.

There has been an alarming increase in the incidence of inflammatory bowel diseases (IBDs) worldwide over the past several decades. The pathogenesis of IBD involves genetic and environmental factors. Diet is a potentially modifiable environmental risk factor for IBD onset and severity. Diet can promote intestinal inflammation by dysregulating the immune system, altering intestinal permeability and the mucous layer, contributing to microbial dysbiosis, and other mechanisms. Dietary changes therefore might be incorporated into therapeutic strategies for IBD. Enteral nutrition is effective in the treatment of pediatric patients with luminal Crohn's disease, but there have been few studies of the effects of dietary interventions with whole foods-most of these have been studies of exclusion diets in patients with Crohn's disease. We review findings from studies of the effects of dietary patterns, single micronutrients, and food additives in inducing and maintaining remission in patients with IBD. We discuss future directions for research and propose a framework for studies of dietary interventions in the treatment of IBD.

Systematic review with meta-analysis: Nutritional screening and assessment tools in cirrhosis.

BACKGROUND & AIMS: Disease-related malnutrition is common in cirrhosis. Multiple studies have evaluated nutritional screening tools (NSTs, rapid bedside tests targeting who needs assessment) and nutritional assessment tools (NATs, used in diagnosing malnutrition) as predictors of clinical outcome in this population. We performed a systematic review and meta-analysis of this literature with the aim of summarising the varying definitions of malnutrition across studies, the available evidence for NSTs and the ability of NSTs and NATs to predict clinical outcomes in cirrhosis. METHODS: The primary outcome measures were pre- and post-transplant mortality with a range of secondary outcomes. Inclusion: cirrhosis over age 16. Exclusion: >25% with hepatocellular carcinoma, primarily laboratory test-based NATs or lack of screening, assessment or outcome criteria. RESULTS: Eight thousand eight hundred fifty patients were included across 47 studies. Only 3 studies assessed NSTs. Thirty-two definitions for malnutrition were utilised across studies. NATs predicted pre-transplant mortality in 69% of cases that were assessed with a risk ratio (RR) of 2.38 (95% CI 1.96-2.89). NATs were prognostic for post-transplant mortality only 28% of the times they were assessed, with a RR of 3.04 (95% CI 1.51-6.12). CONCLUSIONS: The cirrhosis literature includes limited data on nutrition screening and multiple definitions for what constitutes malnutrition using NATs. Despite this discordance, it is clear that malnutrition is a valuable predictor of pre-transplant mortality almost regardless of how it is defined. We require clinical and research consensus around the definition of malnutrition and the accepted processes and cut-points for nutrition screening and assessment in cirrhosis.

Yoga as a Therapy for Irritable Bowel Syndrome.

The aim of this state-of-the-art narrative review is to evaluate the current evidence about the effectiveness of yoga as therapy for IBS and explore its potential mechanisms of action. The current literature suggests yoga is effective and safe and may target multiple mechanisms involved in treatment of IBS. Evidence from randomized controlled trials identified yoga as more effective compared to pharmacological treatment and equally effective as dietary interventions or moderate-intensity walking. Improvements were seen in both physical health (IBS symptom severity, gastric motility, autonomic and somatic symptom scores, and physical functioning) and mental health outcomes (depression, anxiety, gastrointestinal-specific anxiety, and quality of life). Given favorable changes in IBS-related physical and mental health outcomes, preliminary data supports yoga as beneficial in this population. However, the relatively low-quality evidence resulting from heterogeneity of study designs, interventions, and outcome measures limit our ability to make specific recommendations about the use of yoga as therapy for patients with IBS.

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.

A practical approach to nutritional screening and assessment in cirrhosis.

Malnutrition is one of the most common complications of cirrhosis, associated with an increased risk of morbidity and mortality. As a potentially modifiable condition, it is of particular importance to identify malnourished patients so that nutritional therapy can be instituted. Nutrition screening and assessment are infrequently performed in patients with cirrhosis. The reasons for this are multifactorial, including the absence of a validated "rapid" screening tool, multiple definitions of what constitutes malnutrition, and challenges with interpreting body composition and laboratory results in the setting of volume overload and liver dysfunction. This article summarizes the clinically relevant evidence and presents key issues, tools, and clinical options that are applicable to patients with cirrhosis. The definition, etiology, and clinically relevant outcomes associated with malnutrition are reviewed. Rapid nutritional screening is differentiated from more detailed nutritional assessment. Nutritional assessment in special populations, including women and the obese, and the role of inflammation are discussed. Multicenter studies using a common nutritional screening/assessment strategy are the next steps to fast-track adoption and implementation of nutrition-related evaluations into routine clinical practice. (Hepatology 2017;65:1044-1057).

Sarcopenic obesity in cirrhosis-The confluence of 2 prognostic titans.

Sarcopenia and obesity are 2 major health conditions with a growing prevalence in cirrhosis. The concordance of these 2 conditions, sarcopenic obesity, is associated with higher rates of mortality and impact on the metabolic profile and physical function than either condition alone. To date, there is little consensus surrounding the diagnostic criteria for sarcopenia, obesity or as a result, sarcopenic obesity in patients with cirrhosis. Cross-sectional imaging, although the most accurate diagnostic technique, has practical limitations for routine use in clinical practice. Management strategies are focused on increasing muscle mass and strength. The present review provides an overview of the diagnosis, pathophysiology, prognostic implications and management strategies available for sarcopenic obesity in cirrhosis. We also discuss the associated condition myosteatosis, the pathological accumulation of fat in skeletal muscle. Much work needs to be done to advance both clinical care and research in this area. Future directions require consensus definitions for sarcopenia, obesity and sarcopenic obesity, an expansion of our understanding of the complex pathogenesis of the muscle-liver-adipose tissue axis in cirrhosis and evidence to support management recommendations for nutrition, exercise and pharmacological therapies.

Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol.

BACKGROUND: Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. METHODS/DESIGN: In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. DISCUSSION: There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.

Association between protein intake and functional capacity in critically ill patients: A retrospective cohort study.

BACKGROUND: Intensive care unit (ICU) protein benchmarks are based on mortality and morbidity; whether these targets also support functional recovery is unknown. We assessed whether different protein doses influenced patients' functional capacity, measured by the Chelsea Physical Assessment score (CPAx). METHODS: Single-center retrospective cohort study on ICU survivors with length of stay ≥7 days admitted between October 2014 and September 2020. Eligible patients were divided according to protein intake (g/kg/day): low (<0.8), medium (0.8-1.19), high (1.2-1.5), and very high (>1.5). Protein dose effect on CPAx was assessed at ICU discharge with analysis of covariance adjusting for age, illness severity, hospital length of stay before ICU admission, time to start nutrition support, and mechanical ventilation duration. We also investigated effect modification by energy intake and nutrition status. RESULTS: Enrolled patients (n = 531) were similar for age, nutrition status, and illness severity across groups. CPAxs were nonlinearly associated with protein doses and similar among low, medium, and very high groups. The CPAx for the high group was statistically different (P = 0.014), indicating that the data of three groups could be pooled. Mean CPAx difference remained statistically significant after adjusting for confounding variables (3.9 ± 1.8, P = 0.029 in the four-group model, and 2.7 ± 0.9, P = 0.003 in the pooled two-group model). Energy intake was equivalent between groups and did not modify CPAx. The high group had superior CPAx in both well-nourished and malnourished patients, indicating nutrition status was not an effect modifier. CONCLUSION: Protein dose 1.2-1.5 g/kg/day was associated with superior functional capacity at ICU discharge compared with other doses. Neither energy intake nor nutrition status modified functional capacity across groups; therefore, the results appear to be influenced by 1.2-1.5 g/kg/day.