Chedid, Victor

AbstractBackgroundPatients with pelvic floor myofascial pain (PFMP) have puborectalis tenderness on digital rectal examination (DRE). Little is known about its significance to anorectal function in patients presenting with constipation.AimTo characterize demographics, clinical characteristics, findings on anorectal manometry (ARM), diagnosis of rectal evacuation disorder (RED), colonic transit [normal (NTC) or slow (STC)], and imaging in constipated patients with PFMP and compare these features to constipation without PFMP.MethodsWe performed an electronic medical records review of patients with constipation evaluated by a single gastroenterologist between January 2008 and February 2019. Patients with PFMP were compared to controls with constipation but without PFMP (1:2 ratio).Key ResultsA total of 98 PFMP cases and 196 controls were identified. Constipated patients with PFMP were more likely to have RED [OR 7.59 (3.82‐15.09), P < .01]; controls were more likely to have either NTC [OR 4.25 (1.45‐12.42), P < .01] or STC [OR 3.57 (1.45‐8.78), P < .01]. RED in patients with PFMP is supported by comparison to controls: On DRE, they had increased resting tone [OR 2.25 (1.33‐3.83), P < .01] and paradoxical contraction of the puborectalis upon simulated evacuation [OR 3.41 (1.94‐6.00), P < .01]; on ARM, they had higher maximum resting pressure (102.9 mmHg vs 90.7 mmHg, P < .01) and lower rectoanal pressure gradient (−39.4 mmHg vs −24.7 mmHg, P < .01).Conclusions/InferencesIn constipated patients, PFMP is highly associated with RED. Its presence provides a valuable clue regarding the etiology of a patient's constipation; it should be assessed in all patients with constipation and should also be an additional target for management.

Abstract Purpose Obesity is associated with alterations in appetite, gastrointestinal hormone levels and excessive fat mass. We previously published a double-blind, placebo-controlled, randomized, 16-week trial on effects of once-daily glucagon-like peptide-1 (GLP-1) analog, liraglutide on weight, satiation, and gastric functions in obese volunteers. The aim of this substudy is to compare to placebo the effects of liraglutide on appetite, taste preference, regional body fat stores, and anthropometric measurements. Methods Forty obese adults received standard instruction for weight management, monthly behavioral intervention utilizing motivational interviews, and 16-week treatment of once-daily liraglutide (escalated to 3 mg SQ daily). At baseline and 16 weeks, the following were measured: appetite and taste preferences rated every 30 min for 5 h after ingesting 300 mL Ensure®; maximal tolerated volume (MTV) with a nutrient drink test; fasting and postprandial bioactive GLP-1 (7–36) and peptide YY (PYY) levels; total and regional body fat with dual-energy X-ray absorptiometry, and waist and hip circumference. Results Thirty-five participants (17 liraglutide; 18 placebo) completed the trial. Compared to placebo group, liraglutide group had significant reductions in MTV; prospective food consumption score; desire to eat something sweet, salty, savory or fatty; and an increase in perceived fullness. Postprandial plasma levels of GLP-1 decreased and PYY levels increased with liraglutide relative to baseline. Significant reductions in total body, trunk, and upper and lower body fat without reduction in lean body mass were observed. Conclusion Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.

LINKED CONTENTThis article is linked to Sebastian et al papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15498.

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.

INTRODUCTION: Aquaporin (AQP) channels are involved in regulating fluid homeostasis in the colon. Several AQP channels were detected in human colon epithelial cells. In a previous study, rats fed 1% (wt/wt) sodium cholate had increased AQP3, 7, and 8 levels, suggesting AQP involvement in bile acid diarrhea (BAD). Our aim was to compare AQP expressions in rectosigmoid mucosal (RSM) biopsies from patients with irritable bowel syndrome–diarrhea (IBS-D) (divided into those with normal or high fecal BA excretion) and in patients with IBS-constipation (IBS-C) compared with healthy controls. METHODS: In RSM biopsies from 44 patients with IBS-D (with normal (<) or high (>2,337 μmol/48 hours (BAD)) fecal BA excretion), 10 patients with IBS-C, and 17 healthy controls, we measured expressions of AQP1, 3, 7, and 8, with RT-PCR (housekeeper gene GAPDH ). We analyzed RNA for expression by RT 2 -PCR assays, with expression calculated using 2 −ΔΔCT -based fold-change. Comparisons of IBS groups were corrected for false detection rate (Bonferroni correction for 12 comparisons; P < 0.0042). AQP protein measurements on biopsies from 3 healthy controls, 3 patients with IBS-D, and 3 patients with BAD were performed by western blots (GAPDH housekeeping protein). RESULTS: In RSM from patients with IBS-D (but not IBS-C), mRNA expression of AQP3 was decreased, and AQP7 and 8 were increased relative to controls. Fold differences were not different in IBS-D with or without BAD. Western blots confirmed increased expression of AQP7 and 8 and decreased AQP3 proteins in biopsies from patients with IBS-D compared with controls. CONCLUSIONS: Increased AQP7 and 8 and decreased AQP3 expressions in RSM suggest that further studies on AQPs' potential role in the pathophysiology of diarrhea in IBS-D are warranted.

AbstractObjectiveTo compare estimates of gastric accommodation (GA) with single photon emission computed tomography (SPECT) to measurements based on intragastric meal distribution immediately post‐meal ingestion (IMD0).MethodsWe evaluated 108 diabetics with upper gastrointestinal (UGI) symptoms who had undergone gastric emptying of solids (GE) by scintigraphy and GA measurements by SPECT. Immediately after ingestion of a 99mTc‐labeled egg meal (time 0), we estimated IMD0 as radioactive counts or area of the proximal half of the stomach on two‐dimensional images. Gastric volume (GV) during fasting and after 300 mL Ensure® was measured by SPECT to quantify accommodation volume (AV) or postprandial to fasting volume ratio (GVR). From the measured proximal gastric area, we estimated the volume of proximal stomach (4/3 × π × r3). We performed regression analyses to assess relationships between IMD0 and GA (AV) and GVR.ResultsThere was a significant correlation between area and radioactivity counts in the proximal stomach (r = 0.67, P < 0.001); however, there was considerable interpersonal variation [bias 0.20 (95% CI −0.07, 0.47)]. There were no significant correlations between total GV or AV or VR by SPECT and measurements using IMD0: proximal gastric counts, area, and estimated volume as continuous variables of dichotomized patient groups, based on published cutoff values. There were no significant differences in total gastric area or the IMD0 parameters (% area or % radioactive counts) between those with and without UGI symptoms except for fullness and satiety.ConclusionsIntragastric meal distribution immediately post‐meal ingestion is not significantly correlated with GA measurement by SPECT.

AbstractBackgroundBalloon expulsion test (BET) and high‐resolution anorectal manometry (HRM) are used in diagnosis of rectal evacuation disorders (REDs); their performance characteristics are suboptimal.MethodsWe audited records of 449 consecutive patients with chronic constipation (CC). We documented anal sphincter tone and contraction, puborectalis tenderness, and perineal descent on digital rectal exam (DRE); maximum resting and squeeze pressures, and rectoanal pressure gradient on HRM; weight or time to balloon expulsion; colonic transit, and area of rectal area on radiograph (RASF). We based the diagnosis of RED on ≥2 abnormalities on both DRE and HRM, excluding results of BET, as the performance of BET is being investigated. Results of RED vs non‐RED and results obtained using tbBET vs wbBET groups were compared. We used multivariate logistic regressions to identify predictors of RED using different diagnostic modalities.Key ResultsAmong 449 individuals, 276 were included (74 RED and 202 non‐RED). Predominant exclusions were for no HRM (n = 79) or use of low resolution anorectal manometry (n = 77). Logistic regression models for abnormal tbBET showed time >60 seconds, RASF and age‐predicted RED. For tbBET, the current cutoff of 60 seconds had sensitivity of 39.0% and specificity 93.0% to diagnose RED; on the other hand, applying the cutoff at 22 seconds, the sensitivity was 77.8% and specificity 69.8%.Conclusions & InferencesThe clinical diagnosis of RED in patients with CC is achieved with combination of DRE, HRM and an optimized, time‐based BET. Prospective studies are necessary to confirm the proposed 22 second cutoff for tbBET.