No 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.

Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003–2015). Patient data collected included the type of HE, medications, Model for End-Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1–4 months), and longer-term (6–12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty-five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1–4 and 6–12 months, respectively. The majority (67%; 8/12) were free from HE-related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE.

Background & Aims Approximately one-third of patients who present with constipation to gastroenterology care have rectal evacuation disorders. We aimed to compare rectal gas volume, measured by computerized tomography (CT), in constipated patients with and without rectal evacuation disorders. Method In a retrospective study, we collected data from 1553 patients with constipation, evaluated over 20 years. We analyzed data from 141 patients evaluated by anorectal manometry, balloon expulsion tests, and colon transit tests, collecting records of abdominal and pelvic CT examinations. Patients were classified into 3 subgroups: those with rectal evacuation disorders, slow transit constipation, or normal transit constipation. Two observers used standard CT software to identify variable regions of interest on each cross-sectional CT image that contained rectum and measured areas of gas in each slice; they then summated entire volumes of rectal gas. For the 3 groups, we compared rectal gas volume, maximal rectal gas transaxial area (measured by CT), and area of rectal gas (vertical) on the 2-dimensional abdominal film (scout) using the Kruskal Wallis test. Results The intra-class correlation coefficient between 2 observers' measurements of rectal gas volume was 0.99 (P<.001). There were overall group differences in rectal gas volume and maximal rectal gas transaxial area (both P<.001). Median rectal gas volume was higher in patients with rectal evacuation disorders (13.84 cm3) than in patients with slow transit (2.51 cm3) or normal transit constipation (1.33 cm3, both P<0.05). Similarly, area of rectal gas, which correlated with maximal rectal gas transaxial area (Spearman correlation coefficient, 0.7; P<.001), showed overall 3-group differences (P=.033), with greater areas of rectal gas on the abdominal scout film in patients with rectal evacuation disorders than in those with normal transit constipation. Conclusion In an analysis of patients with constipation, we found rectal gas volume, determined by abdominal CT imaging, to be greater in patients with than without rectal evacuation disorders.

NGM282 significantly impacts GE and colonic transit, consistent with the observed clinical symptoms. The specific mechanism of prokinetic activity requires further research.