The Natural History of Chronic Unexplained Gastrointestinal Disorders and Gastroesophageal Reflux During 20 Years: A US Population-Based Study.

Objective: To explore the natural history of chronic unexplained gastrointestinal (GI) symptoms and to determine the longitudinal trends of prevalence during a 20-year period in a single US community.

Methods: Between January 1, 1990, and December 31, 2009, valid self-report questionnaires of GI symptoms were mailed to randomly selected cohorts of a community. The study used respondents who answered questions on 1 or more of 3 surveys (initial, 1990-1992; second, 2003-2004; and third, 2008-2009).

Relationship between symptoms during a gastric emptying study and intestinal chemosensitivity with daily symptoms.

Background: Non-ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon-like peptide-1 (GLP-1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP-1 mediates symptoms during duodenal lipid infusion in NUD.

Randomised clinical trial: pregabalin vs placebo for irritable bowel syndrome.

Background: Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking.

Aim: To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients.

GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist.

Context: Delayed gastric emptying (GE) is common but often asymptomatic in diabetes. The relationship between symptoms, glycemia, and neurohormonal functions, including glucagonlike peptide 1 (GLP-1), are unclear.

Objectives: To assess whether GE disturbances, symptoms during a GE study, and symptoms during enteral lipid infusion explain daily symptoms and whether GLP-1 mediates symptoms during enteral lipid infusion.

Aging, Obesity, and the Incidence of Diverticulitis: A Population-Based Study.

Objective: To understand why the population-based incidence of diverticulitis has increased over time, we studied temporal changes in age, body mass index (BMI), and diverticulitis in Olmsted County, Minnesota.

Participants And Methods: We compared the BMIs of 2967 patients with diverticulitis and 9795 people without diverticulitis from January 1, 1980, through December 31, 2007. Because BMI is a surrogate for adipose tissue, computed tomographic estimations of abdominal fat content were compared between 381 diverticulitis cases and 381 age- and sex-matched controls.

A pharmacological challenge predicts reversible rectal sensorimotor dysfunctions in women with fecal incontinence.

Background: In order to understand the pathophysiology of rectal sensorimotor dysfunctions in women with fecal incontinence (FI) and rectal urgency, we evaluated the effects of a muscarinic antagonist and an adrenergic α agonist on these parameters.

Methods: Firstly, rectal distensibility and sensation were evaluated with a barostat and sinusoidal oscillation at baseline and after randomization to intravenous saline or atropine in 16 healthy controls and 44 FI patients. Thereafter, FI patients were randomized to placebo or clonidine for 4 wk; rectal compliance and sensation were revaluated thereafter.

Reproducibility of gastric emptying assessed with scintigraphy in patients with upper GI symptoms.

Background: The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter-individual reproducibility of these parameters in patients with upper gastrointestinal symptoms.

Methods: Sixty patients (21 diabetics, 39 non-diabetics) with upper gastrointestinal symptoms underwent scintigraphic-assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days.

Effects of NGM282, an FGF19 variant, on colonic transit and bowel function in functional constipation: a randomized phase 2 trial.

Objective: NGM282 is an analog of fibroblast growth factor 19 (FGF19), a potent inhibitor of bile acid (BA) synthesis in animals and humans. In phase 2 trials in type 2 diabetes and primary biliary cholangitis, NGM282 was associated with dose-related abdominal cramping and diarrhea. We aimed to examine effects of NGM282 on colonic transit, stool frequency and consistency, hepatic BA synthesis (fasting serum C4), fecal fat, and BA in functional constipation (FC).

Normal values for assessment of anal sphincter morphology, anorectal motion, and pelvic organ prolapse with MRI in healthy women.

Background: Endoanal MRI and MR defecography are used to identify anal sphincter injury and disordered defecation. However, few studies have evaluated findings in asymptomatic healthy people. The effects of BMI and parity on rectoanal motion and evacuation are unknown.

Allelic variant in the glucagon-like peptide 1 receptor gene associated with greater effect of liraglutide and exenatide on gastric emptying: A pilot pharmacogenetics study.

Background: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide.

Methods: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T and weight from two trials that evaluated separately exenatide, 5 μg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks.

Effects of Antidepressants on Gastric Function in Patients with Functional Dyspepsia.

Background: Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood.

Aims: Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology.

Effects of Amitriptyline and Escitalopram on Sleep and Mood in Patients With Functional Dyspepsia.

Background & Aims: Tricyclic antidepressants are effective in reducing symptoms of functional dyspepsia (FD). We performed a post hoc analysis of data from a previous randomized clinical trial to determine whether the benefits of an antidepressant on gastrointestinal symptoms in patients with FD were mediated by improving sleep or reducing anxiety. We explored the relationships between psychological measures, quality of sleep, and relief of symptoms.

Identification and validation of functional gastrointestinal disorder subtypes using latent class analysis: a population-based study.

Objective: Attempts to categorize distinct functional gastrointestinal disorders based on reported symptoms continue but symptoms frequently overlap. The study objective was to use latent class analysis (LCA) which accommodates both continuous and discrete manifest variables to determine mutually exclusive subgroup assignments of a population-based sample using gastrointestinal symptom and patient data.

Materials And Methods: A validated bowel disease questionnaire and somatic symptom questionnaire were mailed to an age and gender stratified randomly selected community sample.

Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial.

Background: Liraglutide, a long-acting GLP-1 receptor agonist, is approved for treatment of obesity; however, the mechanisms of action of liraglutide are incompletely understood. We compared effects of liraglutide versus placebo on gastric motor functions, satiation, satiety, and weight in obese individuals over 16 weeks.

Methods: We did a randomised, double-blind, placebo-controlled pilot trial at a single centre (Mayo Clinic, Rochester, MN, USA).

Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health.

The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total = 285, 73% women, mean BMI 33.5 kg/m): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing.

Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.

Objectives: The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response.

Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study.

Background: It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs-gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community.

Methods: A population-based study was conducted by mailing a valid GI symptom questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN.

A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation.

Background: In an open-label study of 26 patients with IBS-C and chronic constipation, treatment with a vibrating (VIBRANT) capsule twice a week for 7.5 weeks resulted in 88.5% responders.

Opioid analgesic use among patients presenting with acute abdominal pain and factors associated with surgical diagnoses.

Background: The prevalence of chronic opioid use among non-cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non-cancer patients presenting with AAP to an emergency department (ED).

Methods: We performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP.

Low Risk of Pneumonia From Pneumocystis jirovecii Infection in Patients With Inflammatory Bowel Disease Receiving Immune Suppression.

Background & Aims: Use of immunosuppressants and inflammatory bowel disease (IBD) may increase the risk of pneumonia caused by Pneumocystis jirovecii (PJP). We assessed the risk of PJP in a population-based cohort of patients with IBD treated with corticosteroids, immune-suppressive medications, and biologics.

Methods: We performed a population-based cohort study of residents of Olmsted County, Minnesota, diagnosed with Crohn's disease (n = 427) or ulcerative colitis (n = 510) from 1970 through 2011.

Colonic Transit and Bile Acid Synthesis or Excretion in Patients With Irritable Bowel Syndrome-Diarrhea Without Bile Acid Malabsorption.

Background And Aims: Bile acids (BAs) are passively absorbed to a different extent along the mammalian colon, so that levels are lower in the feces than in proximal colon. Our aim was to explore associations among total, primary, and secretory BA in stool and colonic transit in patients with irritable bowel syndrome-diarrhea (IBS-D) without overt BA malabsorption (BAM).

Methods: In a cross-sectional observational study of 116 patients with IBS-D recruited from local communities in Minnesota, we measured total and individual main fecal BA excretion, fecal fat and fecal weight over 48 hours, fasting serum levels of C4 (surrogate for BA synthesis), and overall colonic transit by scintigraphy (geometric center at 24 hours and 48 hours).

Effects of hemin on heme oxygenase-1, gastric emptying, and symptoms in diabetic gastroparesis.

Background: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis.

The incidence rate and characteristics of clinically diagnosed defecatory disorders in the community.

Background: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community.

High-resolution Anorectal Manometry for Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women.

Background & Aims: Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high-resolution manometry (HRM) for diagnosing defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities.

Methods: We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013.

Reproducibility of high-definition (3D) manometry and its agreement with high-resolution (2D) manometry in women with fecal incontinence.

Background: While widely used in clinical practice, the reproducibility of high-definition anorectal manometry (HD-ARM) remains unclear. We evaluated the intra-individual reproducibility of HD-ARM and compared pressures measured with HD-ARM and high-resolution anorectal manometry (HR-ARM).

Methods: Thirty-six women with fecal incontinence had an initial HD-ARM (HD-ARM1); on the same day, after randomization, 21 had a second (HD-ARM2).