Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

BACKGROUND AND AIMS: Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. METHODS: 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. RESULTS: We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. CONCLUSIONS: In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

Relationship between dietary intake components and hepatic fibrosis in those with obesity before and 1 year after bariatric surgery.

OBJECTIVES: Non-alcoholic fatty liver disease is highly prevalent in the bariatric population but not all patients develop liver fibrosis. Considering that fibrosis may affect clinical outcomes, it is important to assess and treat contributing factors. In this population, it is not clear whether dietary intake is a contributor. The objective was to determine the relationship between dietary intake components and liver fibrosis before and 1 y after Roux-en-Y gastric bypass (RYGB). METHODS: This was a prospective cross-sectional (n = 133) study conducted between 2013 and 2022. In addition, a subgroup of 44 patients were followed for 1 y post-RYGB. Anthropometrics, biochemical measurements, and 3-d food records and liver biopsies were obtained presurgery and, in a subgroup of patients, as for the cohort, 1 y post-RYGB. RESULTS: In the cross-sectional study, 78.2% were female, with a median age of 48 y and body mass index of 46.8 kg/m2; 33.8% had type 2 diabetes mellitus and 57.1% had metabolic syndrome. In a multivariate analysis, age (odds ratio; 95% CI) (1.076; 1.014-1.141), alanine transaminase (1.068; 1.025-1.112), calorie intake (1.001; 1.000-1.002), and dietary copper (0.127; 0.022-0.752) were independently associated with fibrosis (<0.05). At 1 y post-RYGB, no independent risk factors were associated with persistent fibrosis. CONCLUSIONS: In bariatric patients before surgery, higher age, alanine transaminase, and total calorie and lower copper intakes were independent risk factors associated with liver fibrosis. These relationships were no longer observed after RYGB, likely due to the effect of surgery on weight and similar postsurgery diet among patients.

Adipose Tissue and Plasma Markers Associated with HbA1c Pre- and Post-bariatric Surgery: a Cross-sectional and Cohort Study.

PURPOSE: Obesity can be associated with chronic inflammation and dysregulated expression of inflammatory adipokines that contribute to insulin resistance and type 2 diabetes. This may also affect the clinical response to bariatric surgery. Our objective was whether baseline visceral adipose tissue features and plasma adipokine are associated with HbA1c ≥0.06 at the time of Roux-en-Y gastric bypass (RYGB) surgery and with persistently elevated HbA1c at 12 months post-RYGB. METHODS: During the surgery, adipose biopsies and plasma were collected for adipokine/cytokine profile. Clinical and biochemical measurements were also collected at the time of RYGB and, in those with baseline elevated HbA1c, at 12 months post-RYGB. RESULTS: In the cross-sectional study, 109 patients (82.6% female; age 49 years; BMI 46.98 kg/m2) participated. Of those with elevated HbA1c at baseline (n = 61), 47 patients had repeated measurements at 12 months post-RYGB (23% drop-out). Using a multivariate logistic regression model, older age (adjusted odds ratio (aOR), 1.14; 95% confidence interval (CI), 1.06-1.22) and higher plasma resistin (aOR, 5.30; 95% CI, 1.25-22.44) were associated with higher odds of HbA1c ≥ 0.06, whereas higher plasma adiponectin (aOR, 0.993; 95% CI, 0.99-0.996) was associated with lower odds of HbA1c ≥0.06. In addition, baseline higher average adipose cell area (aOR, 1.0017; 95% CI, 1.0002-1.0032) and plasma resistin (aOR, 1.0004; 95% CI, 1.0000-1.0009) were associated with higher odds of having persistently elevated HbA1c at 12 months post-RYGB. CONCLUSION: Our study suggests that baseline plasma adipokine dysregulation, specifically high resistin, and adipocyte hypertrophy may affect the clinical response to RYGB.

Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure.

Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.

Comparing mixed oil to soybean oil lipid emulsion in patients on home parenteral nutrition: a pilot prospective double-blind, crossover, randomized trial.

BACKGROUND: Home parenteral nutrition (HPN) can be associated with increased liver enzymes, catheter-related bloodstream infections (CRBSI), and hospitalizations. Mixed oil (MO) versus soybean oil (SO) lipid emulsion reduces risks in hospitalized patients, but there are no randomized double-blinded controlled trials in HPN. Therefore, the primary objective was to test the study's feasibility such as recruitment and retention in the HPN population and the secondary objective was to assess changes in liver enzymes between MO and SO as well as other clinical and biochemical outcomes. METHODS: This 13-month prospective double-blind crossover randomized pilot trial took place in Toronto, Canada. Participants were HPN patients who were a part of the HPN program at Toronto General Hospital. We recruited patients from the HPN program. HPN patients receiving SO were randomized to either MO or SO, and the study duration was 6 months in each arm (MO or SO) with a 1-month washout period resuming SO. As this is a crossover trial design, the patient is his/her own control. The main outcome measures were descriptions of study feasibility, namely the study recruitment and retention. We also collected biochemical parameters, CRSBI, hospitalization rate, antibiotic use, and mortality. Demographic, nutritional, clinical, and laboratory data were collected at baseline, 3 and 6 months of each arm. The primary analysis population was defined as the per-protocol population who completed the trial including all lipid measurements. RESULTS: A total of 65 HPN patients were assessed, and 60 met the inclusion criteria for the study. Thirty-five percent (21/60) were randomized using a computer-generated random number sequence generator: 10 participants were randomized to receive SO first while 11 were randomized to receive MO first. At 13 months, 3/10 who received SO first completed the study, whereas 9/11 who received MO first completed the study. This did not meet our a priori criteria for success in recruitment and retention. Between types of lipid emulsions, there were no significant differences in changes in liver enzymes or biochemical and clinical outcomes, despite significant changes in plasma free fatty acid composition reflecting MO or SO. CONCLUSIONS: Overall, this pilot trial demonstrated that the use of a prospective double-blind, crossover, randomized trial design was not feasible to conduct in the HPN population because of difficulties in recruiting and retaining patients. In addition, there was no significant impact of MO versus SO lipid emulsion on liver enzymes or most parameters. The lack of significance may be attributed to low sample size from low recruitment and high drop-out rate, short study duration (6 months/arm), and complex care. In a future definitive trial, a multicenter study of longer duration and a larger sample size is recommended, and drop-outs may be reduced by using a parallel study design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02796833. Registered on 13 June 2016-retrospectively registered.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

PURPOSE: Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS: This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS: One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION: Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.

AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy. MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index ≥ 35 kg/m2 and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n = 15) or autologous FMT (their own stool; n = 13) delivered in the caecum and were followed for 3 months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores. RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P < 0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P < 0.05) but not in the autologous group. CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.

Comparison of bioelectrical impedance analysis, mass index, and waist circumference in assessing risk for non-alcoholic steatohepatitis.

OBJECTIVE: Non-alcoholic fatty liver disease is a leading cause of liver disease worldwide and includes nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Because NASH is associated with obesity severity, routine evaluation of obesity/body fat in clinical settings may help detect patients at risk. The aim of this study was to determine whether assessing body fat by bioelectrical impedance analysis (BIA) is superior to body mass index (BMI) and waist circumference (WC) in assessing the risk for NASH. METHODS: In this cross-sectional study, patients were recruited and gave consent from a local hospital. All had a liver biopsy. Measurements before the biopsy included BMI, WC, and BIA. BIA was used to measure percentage body fat and fat mass (kg). Based on histology, patients were grouped into one of three categories: simple steatosis (SS), NASH, or normal liver (NL). RESULTS: Of the 139 participants who participated, 39 were classified as SS, 53 as NASH, and 47 as NL. Regardless of sex, patients with NASH had significantly higher BMI, WC, percentage body fat and fat mass than those with NL or SS. These four parameters were significantly positively correlated with liver histology measurements. In all patients, when controlling for sex and age we found that BMI, WC, and BIA were equal at predicting the presence of NASH (P = 0.0571). CONCLUSION: All three methods, BIA, BMI, and WC, were comparable in assessing the risk for NASH. For practical purpose in clinical settings, using BMI is acceptable.

The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial.

BACKGROUND: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population. METHODS AND DESIGN: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months. DISCUSSION: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression. TRIAL REGISTRATION: Clinical Trials Gov NCT03279224.

Home parenteral nutrition patients on mixed oil lipid emulsion have a higher rate of hospitalizations compare to those on soybean oil- a prospective 2-year cohort study.

BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).

Olive oil-based lipid emulsion is noninferior to soybean oil-based lipid emulsion in the acute care setting: A double-blind randomized controlled trial.

OBJECTIVES: Olive oil (OO)-based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)-based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting. METHODS: In this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations). RESULTS: A total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P < 0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P < 0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P < 0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups. CONCLUSIONS: In this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

Factors Affecting Metabolic Outcomes Post Bariatric Surgery: Role of Adipose Tissue.

Obesity is an ever-growing public health crisis, and bariatric surgery (BS) has become a valuable tool in ameliorating obesity, along with comorbid conditions such as diabetes, dyslipidemia and hypertension. BS techniques have come a long way, leading to impressive improvements in the health of the majority of patients. Unfortunately, not every patient responds optimally to BS and there is no method that is sufficient to pre-operatively predict who will receive maximum benefit from this surgical intervention. This review focuses on the adipose tissue characteristics and related parameters that may affect outcomes, as well as the potential influences of insulin resistance, BMI, age, psychologic and genetic factors. Understanding the role of these factors may help predict who will benefit the most from BS.

The effect of malnutrition at admission on length of hospital stay among adult patients in developing country: A prospective cohort study.

BACKGROUND: Malnutrition in hospitalized adults is a highly prevalent problem. During hospital admission, nutritional care and nutritional screenings are often overlooked components of the health care facilities in developing countries. Identifying patients who are at risk of malnutrition at admission are vital to ameliorate clinical outcomes. Therefore, the present study was aimed at assessing the magnitude of hospital malnutrition at the time of admission and evaluates its effect on the length of hospital stay among adult patients. METHOD: We conducted a prospective cohort study in patients ≥18 years admitted in Tikur Anbessa Specialized hospital in Ethiopia. At admission, patient's nutritional status was assessed within 48 h using the Subjective Global Assessment (SGA). The main clinical outcome, length of stay in hospital (LOS) was captured for patients in days. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on LOS. RESULT: Four hundred seventeen patients were enrolled. Based on Subjective Global Assessment (SGA), 62.1% were malnourished. The mean (SD) length of hospital stay for all patients admitted was 13.84 days ± 7.53, with a significant difference (p < 0.01) in length of stay between malnourished patients and well-nourished patients. Malnourished patients had significantly longer hospital stays (17.2 ± 6.8 days) than well-nourished patients (8.3 ± 4.9 days) during 30 days observations. The multivariate Cox's regression model controlled for age, sex, living conditions, number of medications, and number of diagnostic categories, disease severity score, number of comorbidities and presence of cancer found that malnutrition at admission was independently associated with prolonged LOS (adjusted hazard ratio (AHR), 0.29; 95% CI, 0.22,0.38). CONCLUSION: Malnutrition at admission was highly prevalent and was highly associated with prolonged length of hospital stay. Therefore, it is essential to assess the nutritional status of patients early in admission and to institute appropriate nutritional therapy.

Survival of Patients With Short-Bowel Syndrome on Home Parenteral Nutrition: A Prospective Cohort Study.

BACKGROUND: Survival of patients with short-bowel syndrome (SBS) receiving home parenteral nutrition (HPN) and associated factors have not been reported recently in North America. The objective of this study was to determine the long-term survival of adult patients with SBS as the primary indication for HPN and assess factors that may affect survival by using the Canadian HPN Registry. METHODS: This is a retrospective analysis of prospectively collected data extracted from the HPN registry, prior to approval of teduglutide in Canada. Using only incident cases, survival probabilities were estimated by using the Kaplan-Meier method for both full-cohort and nonmalignant SBS. Log-rank test was also used to test the differences in survival distributions between subgroups in the univariate analysis. To identify potential variables that are affecting survival distribution of patients for the multivariable analysis, Least Absolute Shrinkage and Selection Operator and stepwise selection procedure were used. RESULTS: There were 321 patients with a known duration receiving HPN (total, 2287 years), of whom 218 were entered into the registry within 1 year of initiation of HPN. Of 218 incident cases, 22 had active malignancy, along with SBS, and their survival time was significantly lower than those with nonmalignant SBS (P-value < .0001). The 5-year survival of nonmalignant-SBS patients was 81.9%. In this subgroup, there was no significant association between patients' survival and known intestinal anatomy, age, or sex. CONCLUSION: Patients with nonmalignant SBS who receive HPN have a 5-year survival of >80%. Known intestinal anatomical factors did not affect survival.

Hyposalivation is prevalent in bariatric patients but improves after surgery.

BACKGROUND: Obesity and type 2 diabetes can be associated with poor oral health. This can be because of hyposalivation leading to chronic oral inflammation (OI) and periodontal disease. OBJECTIVE: To assess the prevalence of hyposalivation and OI in individuals undergoing Roux-en-Y gastric bypass (RYGB) and determine the relationship with metabolic and anthropometric parameters before and after RYGB. SETTING: University hospital in Canada. METHODS: This was a cross-sectional and prospective cohort study of 59 patients undergoing RYGB from September 2015 to December 2019. Anthropometric, biochemical, and oral measurements were taken before surgery and 1 and 6 months post RYGB. Oral parameters included salivary flow rate and neutrophil count as marker of OI. RESULTS: Fifty-nine patients were enrolled with 29 completing this study. At baseline, the median age was 47 years and body mass index was 46.5 kg/m2, 52 (88.1%) were female and 14 individuals (23.7%) had type 2 diabetes; 54.2% (n = 32) of patients had hyposalivation and 13.6% (n = 8) had high neutrophil count. Patients with hyposalivation had significantly higher fasting glucose (5.7 mmol/L) compared with those without hyposalivation (5.2 mmol/L) but no difference was found between high versus low neutrophil count. At 6 months post RYGB, all variables except oral neutrophil count significantly improved. Hyposalivation persisted in 7 (24%) individuals. CONCLUSIONS: In our bariatric patients, more than half the patients had hyposalivation before RYGB and this was associated with higher fasting glucose. Hyposalivation improved post RYGB in parallel with improvements in metabolic parameters but there was no change in OI. Increased salivation may reduce the risk of periodontal disease.

Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease in Obese Patients Undergoing Bariatric Surgery.

BACKGROUND: Morbid obesity is associated with multiple comorbidities including obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD). It has been suggested that OSA may contribute to NAFLD pathogenesis due to intermittent nocturnal hypoxia. PURPOSE: The objective of this study was to assess the apnea-hypopnea index (AHI) and lower minimum oxygen saturation, markers of OSA, in patients undergoing bariatric surgery (BSx) with perioperative liver biopsy to detect NAFLD. METHODS: This was a single center cross-sectional study of 61 patients undergoing BSx who consented to have a perioperative wedged liver biopsy. Biochemical, clinical, anthropometric variables, and a sleep study test were performed prior to BSx. RESULTS: NAFLD was diagnosed in 49 (80.3%) patients; 12 had normal liver (NL). Those with NAFLD had significantly higher (p < 0.05) AST (42.6 vs 18.1 U/L) and ALT (35.0 vs 22.1 U/L) but similar clinical, anthropometric, and metabolic parameters to NL. There was a higher AHI (32.03 vs 14.35) and significantly lower minimum oxygen saturation (SaO2) (78.87 vs 85.63) in NAFLD compared with NL (p < 0.05). When assessing associations between OSA parameters and liver histology in NAFLD, AHI correlated significantly with lobular inflammation (p < 0.05). In a multivariate analysis, BMI was significantly correlated with lobular inflammation with mean SaO2 nearing significance. CONCLUSIONS: These results indicate that in a homogeneous bariatric population sample with similar characteristics, those with NAFLD had higher AHI and lower minimum SaO2 compared with NL. AHI correlated with liver inflammation suggesting a potential role for intermittent nocturnal hypoxia in the pathogenesis and progression of NAFLD.

GLIM criteria has fair sensitivity and specificity for diagnosing malnutrition when using SGA as comparator.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) proposed a new framework for diagnosing malnutrition based on combinations of phenotypic and etiologic criteria. The aim of this study was to compare GLIM criteria to Subjective Global Assessment (SGA) judged to be the most validated standardized assessment of malnutrition. METHODS: This is a retrospective analysis of variables extracted from a prospective cohort study assessing malnutrition at admission, in 18 Canadian hospitals. Based on the available parameters, GLIM was compared to SGA using the following combinations of one phenotypic and one etiologic criteria: A. weight loss and low intake; B. weight loss and high C-reactive protein (CRP); C. low body mass index (BMI) and low intake; D. low BMI, high CRP. Data were not available for fat-free mass. Since all patients had acute or chronic active disease as per GLIM etiologic criterion, CRP was used as a more specific measure to define inflammation. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. Data are expressed as mean and Clopper-Pearson exact 95% confidence interval (CI). RESULTS: From 1022 patients in the original dataset, 784 had all considered parameters with a prevalence of malnutrition (SGA B or C) of 45.15% (CI 41.60, 48.70), where severe malnutrition (SGA C) was 11.73% (CI 9.57, 14.20). Using the available GLIM parameters with the above combinations of two-criteria, the prevalence of malnutrition was 33.29% (CI 30.00, 36.71) and severe malnutrition was 19.77% (CI 17.00, 22.70). For all criteria combinations of GLIM together versus SGA, sensitivity was 61.30% (CI 56.0, 66.4), specificity was 89.77% (CI 86.5, 92.5) and PPV was 83.14% (CI 78.0, 87.5) while NPV was 73.80 (CI 69.8, 77.5). Sensitivity was improved when only SGA C for severe malnutrition was used as the criterion (82.61%; CI 73.3, 89.7) but PPV was greatly reduced (29.12%; CI 23.7, 35.0). Similarly, when using GLIM criteria for severe malnutrition only, sensitivity improved (76.09%; CI 66.1, 84.4). Any two criteria combinations of GLIM had much poorer sensitivity with the highest being weight loss + high CRP (46.33%) with a specificity of 93.02% (PPV: 84.54%; NPV: 67.80%), while the combination of low BMI + low intake had the highest specificity (98.84%) but with a sensitivity of 15.54% (PPV 91.67%; NPV: 58.70%). CONCLUSIONS: Based on the CMTF dataset and using SGA as the most validated tool for diagnosing malnutrition, the two criteria combinations used for GLIM in the present study had fair criterion validity for the diagnosis of malnutrition, regardless of severity status. The best combinations were weight loss and high CRP or weight loss and low intake, both having high specificity at diagnosing malnutrition but unacceptably low sensitivity, and thus were considered poor. There may be potential for the full framework to be used to diagnose malnutrition, but individual combinations of two criteria when used exclusively will miss malnourished patients, as defined by SGA.

Optimizing the Care of Malignant Bowel Obstruction in Patients With Advanced Gynecologic Cancer.

PURPOSE: Malignant bowel obstruction (MBO) is a common and distressing complication in women with advanced gynecologic cancer. A pilot, interprofessional MBO program was launched in 2016 at a large Canadian tertiary cancer center to integrate these patients' complex care needs across multiple disciplines and support women with MBO. METHOD: Retrospective analysis to evaluate the outcomes of women with advanced gynecologic cancer who were admitted to hospital because of MBO, before (2014 to 2016: baseline group) and after (2016 to 2018) implementation of the MBO program. RESULTS: Of the 169 women evaluated, 106 and 63 were in the baseline group and MBO program group, respectively. Most had ovarian cancer (n = 124; 73%) and had small-bowel obstruction (n = 131; 78%). There was a significantly shorter cumulative hospital length of stay (LOSsum) within the first 60 days of MBO diagnosis in the MBO program group compared with the baseline group (13 v 22 days, respectively; adjusted P = .006). The median overall survival for women treated in the MBO program was also significantly longer compared with the baseline group (243 v 99 days, respectively; adjusted P = .002). Using the interprofessional MBO care platform, a greater proportion of patients received palliative chemotherapy (83% v 56%) and less surgery (11% v 21%) in the MBO program group than in the baseline group, respectively. A subgroup of women (n = 11) received total parenteral nutrition for longer than 6 months. CONCLUSION: Implementation of a comprehensive, interprofessional MBO program significantly affects patient care and may improve outcomes. Unique to this MBO program is an integrated outpatient model of care and education that empowers patients to recognize MBO symptoms for early intervention.

Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease.

Extreme obesity (EO) (BMI >50 kg/m2) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein-truncating variants (PTVs) and copy number variants (CNVs) in genes/regions previously implicated in NPD in adults with EO (n = 149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO (n = 218) and obesity (O) (BMI 35-50 kg/m2; n = 374) and a Swedish cohort of participants from the community with predominantly O (n = 161). The prevalence of variants was compared with control subjects in the Exome Aggregation Consortium/Genome Aggregation Database. In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7% vs. 2.6% in control subjects (odds ratio [OR] 3.1 [95% CI 2-4.1]; P < 0.0001). In the UCLH EO cohort (intermediate NPD prevalence: 47%), CNV AF (1.8% vs. 0.9% in control subjects; OR 1.95 [95% CI 0.96-3.93]; P = 0.06) was lower than the discovery cohort. CNV AF was not increased in the UCLH O cohort (0.8%). No CNVs were identified in the Swedish cohort with no NPD. These findings suggest that PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO.