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ObjectiveLittle is known about the predictors of response to obesity interventions.MethodsIn 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12‐month, pragmatic, real‐world trial performed in a weight management center, 312 patients were randomly assigned to phenotype‐guided treatment or non‐phenotype‐guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.ResultsFour phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype‐guided approach was associated with 1.75‐fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non‐phenotype‐guided group (difference −6.9% [95% CI −9.4% to −4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype‐guided group compared with 34% with non‐phenotype‐guided treatment group.ConclusionsBiological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.

Background & Goals: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). Study: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (r s ) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. Results: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=−0.53; P=0.04) with complete evacuation in IBS-D. Fiber (r s =0.65; P=0.02) and starch (r s =0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=−0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. Conclusions: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.

INTRODUCTION: Bile acid (BA) diarrhea is the cause in ∼26% of chronic unexplained (nonbloody) diarrhea (CUD) based on 75 SeHCAT testing. To assess fecal BA excretion and healthcare utilization in patients with CUD. METHODS: In a retrospective review of 1,071 consecutive patients with CUD who completed 48-hour fecal BA testing, we analyzed the symptoms, diagnostic tests performed, and final diagnoses. RESULTS: After 135 patients were excluded because of mucosal diseases, increased BA excretion was identified in 476 (51%) of the 936 patients with CUD: 29% with selective increase in primary BA and 22% with increased total BA excretion (35% with normal primary BA excretion). There were no differences in demographics, clinical symptoms, or history of cholecystectomy in patients with elevated total or selective primary fecal BA excretion compared with patients with normal excretion. Before the 48-hour fecal BA excretion test was performed, patients completed on average 1.2 transaxial imaging, 2.6 endoscopic procedures, and 1.6 miscellaneous tests/person. Less than 10% of these tests identified the etiology of CUD. Total fecal BAs >3,033 µmol/48 hour or primary BAs >25% had a 93% negative predictive value to exclude mucosal disease. Among patients with increased fecal BA excretion, >70% reported diarrhea improved with BA sequestrant compared with 26% with normal fecal BA excretion. Patients with selective elevation in primary fecal BAs were 3.1 times (95% confidence interval, 1.5–6.63) more likely to respond to BA sequestrant therapy compared with those with elevated total fecal BAs. DISCUSSION: Increased fecal BA excretion is frequent (51%) in patients with CUD. Early 48-hour fecal BA evaluation has the potential to decrease healthcare utilization in CUD.

INTRODUCTION: Over-the-scope clips (OTSC) are used for closure of fistulas, leaks, and acute perforations, and for GI bleeding. Adverse events include perforation, migration, and ulceration. Little is know about the natural history of OTSCs and no data addressing the longevity of clips is available. We present an interim analysis of our center’s experience with OTSC focusing on natural history. METHODS: OTSCs used from 1/1/2011 to 1/1/2019 were compiled and retrospective chart review undertaken. Primary endpoint was clip retention time (time when the clip was placed to time the clip was last seen or was physically removed). Secondary endpoints were rate of complications and factors that influence clip retention time and clinical success. Cox proportional hazards were used to evaluate variables impacting clip retention. Univariate regression was used to assess potential risk factors for adverse events. RESULTS: A total of 358 OTSC were placed in 299 patients (55.8% male, n = 184) with mean age 64 + 15.3 years. Procedures and indications presented in Table 1. Clip placement was clinically successful in 81% of cases (N = 265). Median time to clip loss as assessed by Kaplan-Meier curve was 267 days (95% CI 196-406) (Figure 1). Adverse events occurred in 34 clip placements (10.7%) and included bleeding (n = 8, 24.2%), perforation (n = 5, 15.2%), ulceration (n = 3, 9.1%), migration (n = 15, 45.5%), and infection (n = 1, 3.0%). Univariate analysis (Table 2) revealed that age, gender, type of clip used (there are 3 types of OTSC), and performing endoscopist did not impact clip retention rate. A size 14 clip had marginally higher rates of retention compared to others. Clips placed in the rectum or esophagus were lost earlier compared to those in the small/large intestine and stomach. Clips placed for fistulas and those associated with adverse event were associated with earlier clip loss. In evaluation of clinical success, clips placed for fistulas had a relative risk of clinical failure of 2.08 (95% CI 1.29-3.36) compared to all other indications. CONCLUSION: OTSCs are retained for a median of 8.9 months with clip location and indication for placement being key factors in time to clip loss. Clips used for fistula closure were more likely to be lost compared to those placed for other indications, less likely to be clinically successful, and more likely to cause a complication. These data help guide decision-making when considering OTSC use across clinical indications.

INTRODUCTION: Patients with inflammatory bowel disease (IBD), whether Crohn's disease (CD) or ulcerative colitis (UC), have known alterations in the enterohepatic circulation of bile acids (BA) that may contribute to chronic diarrhea, but the fecal BA patterns are not well defined. We aimed to audit all patients with IBD who had fecal BA measurements as part of evaluation of chronic diarrhea at a tertiary care center. METHODS: Methods: 65 patients with IBD (18 with UC and 47 with CD) were evaluated at a single center and underwent measurements of fecal total and individual BAs based on a 48-hour collection performed at the end of a 4-day, 100-gram fat diet. The electronic medical records were interrogated to obtain type of IBD, disease activity, location of disease, prior surgery, IBD related therapies, presenting symptoms, and response to treatment with BA sequestrants. Bile acid diarrhea (BAD) diagnosis was based on >10% primary BAs, >4% primary BAs + >1,000 µmol/48 h, or total fecal BAs >2,337 µmol/48 h. IBD disease activity was based on radiologic, endoscopic and histologic parameters. Data are reported as mean ± standard error of the mean (SEM). RESULTS: Table 1 summarizes the patterns of BAD in our cohort with IBD. Figure 1 demonstrates the mean ± SEM of total fecal BAs and % primary BAs in each group of IBD patients. Among patients with UC, 10 had poorly controlled disease and 8 had well controlled disease, and both cohorts had elevated primary BAs (mean 28.9% ± 12.5%; 34.6% ± 21%, respectively). All patients with an ileal pouch anal anastomosis (IPAA) had elevated total fecal BAs (BADt) compared to those with an intact colon. In patients with CD, those with ileal resections had elevated BADt and % primary BAs (6263 µmol/48 h ± 1012 µmol/48 h; 79% ± 5.9%, respectively). Patients with an intact ileum, had elevated % primary BAs regardless of disease activity: controlled CD 34.7% ± 9.3%; poorly controlled CD 57.8% ± 9.5%; 15 out of 47 patients with CD were started on BA sequestrants with a positive response in 10/15. CONCLUSION: Discussion: BAs may play a role in the pathophysiology of chronic diarrhea in patients with IBD, regardless of inflammatory disease activity. Future studies are required to assess the impact of fecal bile acid testing and treatment with BA sequestrants on inflammation and chronic diarrhea in patients with IBD.