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The first coronavirus disease 2019 (COVID-19) pandemic surge harshly impacted the medically underserved populations of the urbanized northeastern United States. Severe acute respiratory syndrome coronavirus 2 virions infect the gastrointestinal (GI) tract, and GI symptoms are common during acute infection.1 Post-COVID syndromes increasingly are recognized as important public health considerations.2 Postinfectious disorders of gut-brain interaction (DGBIs; formerly known as functional gastrointestinal disorders) can occur after enteric illness; the COVID-19 pandemic is anticipated to provoke DGBI development3 within a rapidly evolving post-COVID framework of illness. Here, we evaluate factors associated with DGBI-like post-COVID gastrointestinal disorders (PCGIDs) in our hospital's surrounding communities comprised predominantly of racial/ethnic minorities and those of reduced socioeconomic status.

Introduction : Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases. Methods : Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs). Results : Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group. Discussion : The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.

INTRODUCTION: This post hoc analysis evaluated the effect of prucalopride on abdominal bloating in participants with chronic idiopathic constipation (CIC) who had moderate to very severe bloating at baseline. Methods: Data from 6 phase 3/4 studies of prucalopride in participants with CIC were pooled. Abdominal bloating was assessed weekly using a 5-point scale (0–4). Results: The proportion of bloating responders (≥1-point improvement in abdominal bloating score at week 12) was higher in participants treated with prucalopride (62.1%) vs placebo (49.6%). DISCUSSION: The prucalopride arm had a higher proportion of bloating responders vs placebo in this study population.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (−4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (−15%; P = 0.018) or 325 mg/day (−28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

Background/Aims CSP01 is a novel superabsorbent hydrogel that absorbs gastrointestinal fluids and maintains high viscoelastic properties into the colon, where these fluids are released. Methods We conducted a single-center, randomized, double-blind, parallel-group, placebo-controlled pilot study comparing change in colonic transit time (CTT) among patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) treated for 21 days with either CSP01 hydrogel, active control (carboxymethylcellulose [CMC]) or placebo. CTT was measured using wireless motility capsule transit testing at pre-treatment and end-of-treatment. The primary endpoint was change in CTT. Results Forty subjects (20 CSP01, 11 CMC, 9 placebo) were enrolled and 38 completed the study. There was no significant change in mean CTT by treatment group (P = 0.297). In the placebo group, CTT increased by 15.3 minutes between baseline and end of treatment, increased by 366.4 minutes for CMC, and decreased by 727.4 minutes for CSP01. In post hoc analyses among those with CIC, mean CTT decreased by 1079 minutes for CSP01 (P = 0.025 compared to placebo), 919 minutes for CMC (P = 0.117 compared to placebo) and increased by 1113 minutes for placebo. Among patients with IBS-C, there was no significant difference in change in CTT for any treatment group. One subject in the CSP01 arm developed back pain attributed to constipation and withdrew without a second CTT measurement; there were no other adverse events. Conclusion CSP01 significantly decreased CTT compared to placebo among patients with CIC, but not in patients with IBS-C. (J Neurogastroenterol Motil 2020;26:496-504)

Background Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). Results Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (Ptrend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60–1.17) with five to seven servings per week and 0.62 (95% CI, 0.44–0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41–0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All Pinteraction > 0.055). Conclusion In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with changes in bowel habits. It is the most common GI problem seen by gastroenterologists. IBS is a heterogenous disorder encompassing a spectrum of underlying mechanisms and clinical presentations. The pathophysiology of diarrhea-predominant form of IBS (IBS-D) remains poorly understood, and current available therapeutic options for IBS-D are limited. Eluxadoline is a novel, locally acting mixed μ- and κ-opioid receptor agonist and δ-receptor antagonist approved by the Food and Drug Administration (FDA) for treatment of adults with IBS-D. Data from two phase III clinical trials showed that approximately 25-30% of the eluxadoline-treated patients achieved composite clinical response, defined by a reduction of abdominal pain and improvement in stool consistency. Patients who achieve composite response during the first month of therapy were significantly more likely to demonstrate sustained clinical response. The most common adverse events reported with eluxadoline use were constipation, nausea and abdominal pain. The risk of abuse, dependence, or withdrawal is low. Serious adverse events associated with eluxadoline include sphincter of Oddi spasm (SOS) and pancreatitis particularly in patients without a gallbladder. Development of pancreatitis is likely secondary to SOS, but it remains unclear why pancreatitis occurs so quickly after initial doses. This adverse event profile helps guide proper selection of IBS-D patients for eluxadoline use, with important contraindications including absence of a gallbladder, biliary duct obstruction or sphincter of Oddi dysfunction, alcoholism, history of pancreatitis, or structural diseases of the pancreas. With the recent clinical trials demonstrating its efficacy, eluxadoline provides an additional option to the few existing pharmacologic interventions available for IBS-D. In this review, we discuss the drug development, efficacy and safety of eluxadoline, as well as selection criteria for identifying appropriate candidates for this medication.

Introduction Mortality concern is a frequent driver of care seeking in patients with irritable bowel syndrome (IBS). Data on mortality in IBS are scarce, and population-based studies have been limited in size. We examined mortality in IBS. Methods A nationwide, matched, population-based cohort study was conducted in Sweden. We identified 45,524 patients undergoing a colorectal biopsy at any of Sweden's 28 pathology departments and with a diagnosis of IBS from 2002 to 2016 according to the National Patient Register, a nationwide registry of inpatient and outpatient specialty care. We compared the mortality risk between these individuals with IBS and age- and sex-matched reference individuals (n = 217,316) from the general population and siblings (n = 53,228). In separate analyses, we examined the role of mucosal appearance for mortality in IBS. Finally, we examined mortality in 41,427 patients with IBS not undergoing a colorectal biopsy. Cox regression estimated hazard ratios (HRs) for death. Results During follow-up, there were 3,290 deaths in individuals with IBS (9.4/1,000 person-years) compared with 13,255 deaths in reference individuals (7.9/1,000 person-years), resulting in an HR of 1.10 (95% confidence interval [CI] = 1.05-1.14). After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92-1.00). The risk estimates were neutral when patients with IBS were compared with their siblings. The underlying mucosal appearance on biopsy had only a marginal impact on mortality, and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99-1.06). Discussion IBS does not seem to confer an increased risk of death.

OBJECTIVES:Although the endogenous cannabinoid system modulates bowel function, our understanding of the impact of recreational marijuana (MJ) use on bowel motility is limited. This study examines the effect of MJ on self-reported bowel function among a large cohort of US adults.METHODS:We identifie

Background & Aims Prolonged colon transit times may increase the contact time between potential carcinogens in the stool and the colonic mucosa. Nonetheless, previous studies have yielded conflicting results connecting chronic constipation with the risk of colorectal cancer (CRC). We examined the association between chronic constipation and later CRC. Methods In this nationwide case-control study, we identified 41,299 CRC cases by colorectal biopsy in Sweden between July 2007 and December 2016 and matched them to 203,181 age- and sex-matched controls from the general population. We compared odds of earlier chronic constipation (defined as ≥2 laxative prescriptions in the Prescribed Drug Register with ≥6 months between the first and last prescription) between CRC cases and controls using logistic regression. In separate analyses, we compared odds of earlier constipation between CRC cases and sibling comparators, but also examined earlier risk of having an inpatient/outpatient specialty diagnosis of chronic constipation before CRC. Results Overall, 3943 patients with CRC met our criteria for chronic constipation before CRC. The crude proportion of chronic constipation in CRC patients was 9.5% compared with 8.8% in controls. After multivariable adjustment, there was a modest association between chronic constipation and later CRC (odds ratio [OR], 1.10; 95% CI, 1.06–1.14) that vanished using sibling comparators to control for residual confounding (OR, 1.04; 95% CI, 0.97–1.13). In a sensitivity analysis of 126,650 CRC patients diagnosed from 1989 to 2016, we found no association with earlier chronic constipation diagnosed in inpatient/outpatient specialty clinics (OR, 0.88; 95% CI, 0.75–1.04). Conclusions In a nationwide case-control study, chronic constipation was not associated with later CRC.

Background/Aims: Anxiety and depression are common comorbid psychiatric disorders in IBS patients, but the population-level determinants influencing these comorbidities in IBS patients are poorly understood. We sought to determine whether there was an association between comorbid affective disorders and socioeconomic status among irritable bowel syndrome (IBS) patients. Methods: We assembled a retrospective cohort of 1074 IBS patients with comorbid Generalized Anxiety Disorder (GAD) and/or Major Depressive Disorder (MDD) seen at two tertiary referral centers between 2007 and 2015. IBS patients with comorbid GAD and/or MDD were matched 3:1 by age, sex, and race to controls with IBS and no history of comorbid GAD and/or MDD. Socioeconomic status was approximated by patient zip codes. Results: IBS patients in the lowest socioeconomic group were more likely to be diagnosed with GAD and/or MDD compared to controls (OR = 1.38, p = .0004). The median average per capita income for comorbid GAD/MDD IBS patient cohort was also significantly lower than the control IBS patient cohort ($39,880.50 vs. $41,277.00, p = .02). Conclusions: Among IBS patients, the presence of comorbid Generalized Anxiety Disorder and/or Major Depressive Disorder is associated with lower socioeconomic status and lower average per capita income. These findings speak to a biopsychosocial model of illness, which should be considered by clinicians in the care of IBS patients.

Goals We sought to determine the incidence of jackhammer esophagus (JE) after lung transplantation (LT) and identify potential risk factors for the development of JE after LT. Background JE is a rare esophageal motility disorder, and its pathophysiology remains unclear. Lung transplantation has been implicated as a potential risk factor for JE, but the incidence of JE after LT is unknown. Study A retrospective cohort of adult patients who underwent LT at 2 tertiary care centers over 7.5 years was reviewed. Analysis was performed on patients who underwent a high-resolution esophageal manometry (EM) study before and after LT. JE was defined according to the latest Chicago classification, version 3.0. Results A total of 57 patients without JE identified on pre-LT EM also underwent an EM study after LT. Fifteen (25.4%) were found to have new JE after LT. Patients with newly diagnosed JE after LT were older (61.3±5.3 y vs. 51.6±15.6 y; P=0.02) and more often had chronic obstructive pulmonary disease (COPD; 47.6% vs. 16.6%; P=0.03) compared with those without COPD. There was a trend toward increased risk for JE among female individuals (60% vs. 33.3%; P=0.07) and those with shorter surgical anastomosis times (75.8±12.2 min vs. 84.4±14.3; P=0.06). There was no significant difference between body mass index, opioid use, pretransplant EM findings, surgical ischemic time, occurrence of gastroparesis, or measured post-LT outcomes between the 2 groups. Conclusions JE occurs not uncommonly in patients after LT. Older age and COPD pre-LT may be significant risk factors.

GOALS We sought to determine the efficacy of gabapentin in the treatment of functional dyspepsia among an observational cohort of patients. BACKGROUND Gabapentin has an established role in the treatment of neuropathic pain, with evidence supporting a benefit in visceral hypersensitivity. There is currently no data on the use of gabapentin for the treatment of functional dyspepsia. STUDY Consecutive patients presenting to a tertiary motility clinic for the evaluation of functional dyspepsia without concurrent gastric emptying delay completed a baseline Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) before evaluation and were started on gabapentin for functional dyspepsia by their providers. The primary endpoint was change in total PAGI-SYM score between initial and subsequent visits. RESULTS Of 110 patients enrolled, 62 patients with functional dyspepsia completed pregabapentin and postgabapentin surveys. Subjects' mean PAGI-SYM score decreased by 0.44 (P

BACKGROUND & AIMS: Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19. METHODS: We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition. Systematic chart review determined prevalence, clinical characteristics, and hospital outcomes (ICU complications, length of stay, and mortality) of feeding intolerance. RESULTS: Feeding intolerance developed in 56% of the patients and most commonly manifested as large gastric residual volumes (83.9%), abdominal distension (67.2%), and vomiting (63.9%). Length of intubation (OR 1.05, 95% CI 1.03-1.08), ≥1 GI symptom on presentation (OR 0.76, 95% CI 0.59-0.97), and severe obesity (OR 0.29, 95% CI 0.13-0.66) were independently associated with development of feeding intolerance. Compared to feed-tolerant patients, patients with incident feeding intolerance were significantly more likely to suffer cardiac, renal, hepatic, and hematologic complications during their hospitalization. Feeding intolerance was similarly associated with poor outcomes including longer ICU stay (median [IQR] 21.5 [14-30] vs. 15 [9-22] days, P

Summary Background Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. Methods In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. Findings We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79–1·98) for diagnosis of incident IBD, 1·74 (1·64–1·85) for ulcerative colitis, and 2·27 (2·06–2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07–1·15), two antibiotic dispensations (1·38, 1·32–1·44), and three or more antibiotic dispensations (1·55, 1·49–1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40–1·54) and Crohn's disease (1·64, 1·53–1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28–1·43) for patients who had received three or more dispensations, compared with general population controls. Interpretation Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. Funding National Institutes of Health. Crohn's and Colitis Foundation.

The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement frequency and incident diverticulitis.We studied participants of the Nurses' Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants' medical history, lifestyle factors and diet were used in Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CI).In the NHS during over 24 years of follow-up encompassing 1,299,922 person-years, we documented 5,214 incident cases of diverticulitis, and in the HPFS over 14 years encompassing 368,661 person-years of follow-up, we documented 390 incident cases of diverticulitis. We observed an inverse association between the frequency of bowel movements and risk of diverticulitis. In the NHS, compared with women who had daily bowel movements, those with more than once daily bowel movements had a HR of 1.30 (95% CI, 1.19, 1.42) and those with less frequent bowel movements had a HR of 0.89 (95% CI, 0.82, 0.95; p-trend 0.0001). In the HPFS, the corresponding HRs were 1.29 (95% CI, 1.04, 1.59) and 0.61 (95% CI, 0.36, 1.03; p-trend = 0.003). The association between bowel movements and diverticulitis was not modified by categories of age, BMI, physical activity, laxative use or fiber intake.More frequent bowel movements appear to be a risk factor for subsequent diverticulitis both in men and women. Further studies are needed to understand the potential mechanisms that may underlie this association.

Background The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. Methods Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. Results Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. Conclusions A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. ClinicalTrials.gov Identifier NCT00398801, NCT01696747

Long-term colorectal cancer incidence and mortality after colorectal polyp removal remains unclear. We aimed to assess colorectal cancer incidence and mortality in individuals with removal of different histological subtypes of polyps relative to the general population.We did a matched cohort study through prospective record linkage in Sweden in patients aged at least 18 years with a first diagnosis of colorectal polyps in the nationwide gastrointestinal ESPRESSO histopathology cohort (1993-2016). For each polyp case, we identified up to five matched reference individuals from the Total Population Register on the basis of birth year, age, sex, calendar year of biopsy, and county of residence. We excluded patients and reference individuals with a diagnosis of colorectal cancer either before or within the first 6 months after diagnosis of the index polyp. Polyps were classified by morphology codes into hyperplastic polyps, sessile serrated polyps, tubular adenomas, tubulovillous adenomas, and villous adenomas. Colorectal cancer cases were identified from the Swedish Cancer Registry, and cause-of-death data were retrieved from the Cause of Death Register. We collected information about the use of endoscopic examination before and after the index biopsy from the Swedish National Patient Registry, and counted the number of endoscopies done before and after the index biopsies. We calculated cumulative risk of colorectal cancer incidence and mortality at 3, 5, 10, and 15 years, and computed hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality using a stratified Cox proportional hazards model within each of the matched pairs.178 377 patients with colorectal polyps and 864 831 matched reference individuals from the general population were included in our study. The mean age of patients at polyp diagnosis was 58·6 (SD 13·9) years for hyperplastic polyps, 59·7 (14·2) years for sessile serrated polyps, 63·9 (12·9) years for tubular adenomas, 67·1 (12·1) years for tubulovillous adenomas, and 68·9 (11·8) years for villous adenomas. During a median of 6·6 years (IQR 3·0-11·6) of follow-up, we documented 4278 incident colorectal cancers and 1269 colorectal cancer-related deaths in patients with a polyp, and 14 350 incident colorectal cancers and 5242 colorectal cancer deaths in general reference individuals. The 10-year cumulative incidence of colorectal cancer was 1·6% (95% CI 1·5-1·7) for hyperplastic polyps, 2·5% (1·9-3·3) for sessile serrated polyps, 2·7% (2·5-2·9) for tubular adenomas, 5·1% (4·8-5·4) for tubulovillous adenomas, and 8·6% (7·4-10·1) for villous adenomas compared with 2·1% (2·0-2·1) in reference individuals. Compared with reference individuals, patients with any polyps had an increased risk of colorectal cancer, with multivariable HR of 1·11 (95% CI 1·02-1·22) for hyperplastic polyps, 1·77 (1·34-2·34) for sessile serrated polyps, 1·41 (1·30-1·52) for tubular adenomas, 2·56 (2·36-2·78) for tubulovillous adenomas, and 3·82 (3·07-4·76) for villous adenomas (p0·05 for all polyp subtypes). There was a higher proportion of incident proximal colon cancer in patients with serrated (hyperplastic and sessile) polyps (52-57%) than in those with conventional (tubular, tubulovillous, and villous) adenomas (30-46%). For colorectal cancer mortality, a positive association was found for sessile serrated polyps (HR 1·74, 95% CI 1·08-2·79), tubulovillous adenomas (1·95, 1·69-2·24), and villous adenomas (3·45, 2·40-4·95), but not for hyperplastic polyps (0·90, 0·76-1·06) or tubular adenomas (0·97, 0·84-1·12).In a largely screening-naive population, compared with individuals from the general population, patients with any polyps had a higher colorectal cancer incidence, and those with sessile serrated polyps, tubulovillous adenomas, and villous adenomas had a higher colorectal cancer mortality.US National Institutes of Health, American Cancer Society, American Gastroenterological Association, Union for International Cancer Control.

This cohort study evaluated the joint association of dietary and lifestyle factors with risk of gastroesophageal reflux disease symptoms among women participating in the Nurses’ Health Study II.

Irritable bowel syndrome (IBS) is the most common gastrointestinal (GI) disorder worldwide, however treatment options for diarrhea-predominant IBS (IBS-D) remain limited. Eluxadoline, a µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, was recently approved for the treatment of IBS-D. A novel compound first described in 2008, eluxadoline was shown to normalize GI transit, with a subsequent phase I demonstrating its safety and tolerability in healthy adults. In 2016, two randomized, double-blind, placebo-controlled phase III trials studying eluxadoline use at 75 mg and 100 mg twice daily over 26 weeks demonstrated a significant improvement in stool consistency and many global symptoms of IBS. However, the data did not demonstrate a significant advantage over placebo using the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) endpoints for abdominal pain. Safety and tolerability data, pooled from both phase II and III studies, suggest that eluxadoline is generally well tolerated with the most common adverse events (AEs) occurring in approximately 3–8% of patients and included nausea, constipation, and abdominal pain. The most common serious adverse event (SAE) is pancreatitis, which had a 0.4% incidence. Recent US FDA reports reporting severe pancreatitis and sphincter of Oddi dysfunction after short-term use of eluxadoline in patients without a gallbladder has added a history of cholecystectomy as an important contraindication. Eluxadoline is also contraindicated in patients with a history of biliary duct obstruction, sphincter of Oddi dysfunction, active alcohol abuse, history of pancreatitis or known pancreatic duct obstruction, severe hepatic impairment, severe or chronic constipation, or known mechanical gastrointestinal obstruction. As a new drug to enter the IBS-D market, the place of eluxadoline in the hierarchy of IBS treatments is still to be determined. In this article, we review the development and clinical trial data behind the approval of eluxadoline with a focus on safety data and its use in clinical practice.

Plain film abdominal x-ray (AXR) is frequently used in the evaluation of constipation, but studies assessing the association between stool burden on AXR and colonic transit have been limited. We sought to investigate the relationship between colonic stool burden and slow transit constipation, as determined by a radiopaque marker (ROM) transit study.A retrospective cohort population was assembled, consisting of adult patients with chronic constipation who underwent testing with both a ROM study and anorectal manometry at 2 tertiary care centers over 5 years. Stool burden was graded by 2 independent observers, with colonic transit being assessed by the Hinton method.Of 361 patients, 145 (40.3%) had slow transit constipation, and women were more likely than men to have slow transit constipation (42.3% vs 26.5%, P = 0.04). The mean stool burden scores by observer 1 and observer 2 for patients with slow transit constipation were significantly higher than the mean stool burden scores for patients with normal transit constipation (8.1 ± 1.6 vs 6.9 ± 1.9, P0.0001; 8.5 ± 1.5 vs 5.8 ± 1.6, P0.0001). The Pearson correlation coefficient for the stool burden score and number of remaining ROMs was 0.31 (moderate) for observer 1 (P0.0001) and 0.62 (strong) for observer 2 (P0.0001), whereas the Pearson correlation coefficient for interrater reliability of the stool burden score was 0.58 (P0.0001), indicating a strong correlation. The ideal score cutoff for both observers was 7, with moderate agreement by Cohen's kappa (0.43, P0.0001).Stool burden assessment on AXR may be a reliable alternative ROM study in the assessment of colonic transit.

Background The long-term natural history of microscopic colitis (MC) (collagenous colitis (CC), lymphocytic colitis (LC)), traditionally considered relapsing but non-progressive diseases, is poorly defined. Whether persistent histologic inflammation in such diseases is associated with an increased risk of colorectal neoplasia (CRN) or extracolonic cancers has not been robustly established. Methods This retrospective cohort included diagnosed with MC at a referral center. Rates of CRN and extracolonic cancer were compared to patients undergoing screening colonoscopy (n = 306) and to the United States population using data from the Surveillance, Epidemiology, and End-Results (SEER) program. Standardized incidence ratios (SIR) and 95% confidence intervals were calculated and multivariable regression models used to identify the effect of MC diagnosis and severity on cancer risk. Results Our study included 221 patients with microscopic colitis (112 CC, 109 LC) among whom 77% were women. Compared to the colonoscopy control population, MC was associated with similar odds of tubular adenoma (Odds ratio (OR) 1.07, 95% CI 0.69–1.66) or villous adenoma (OR 1.26, 95% CI 0.17–9.42). Compared to patients with a single episode of MC, those with 2 or more episodes had similar risk of colon cancer (OR 0.83, 95% CI 0.20–3.39) or tubular adenoma (OR 1.49 95% CI 0.83–2.67). We also identified no statistical increase in the rates of cancer in the MC population compared to US-SEER data. Conclusion Microscopic colitis was not associated with increased risk of CRN and extracolonic cancers when compared to controls undergoing colonoscopy or the US SEER population.

BACKGROUND Many patients with fecal incontinence report coexisting constipation. This subset of patients has not been well characterized or understood. OBJECTIVE The purpose of this study was to report the frequency of fecal incontinence with concurrent constipation and to compare quality-of-life outcomes of patients with fecal incontinence with and without constipation. DESIGN This was a prospective cohort study. Survey data, including Fecal Incontinence Severity Index, Constipation Severity Instrument, Fecal Incontinence Quality of Life survey (categorized as lifestyle, coping, depression, and embarrassment), Pelvic Organ Prolapse Inventory and Urinary Distress Inventory surveys, and anorectal physiology testing were obtained. SETTINGS The study was conducted as a single-institution study from January 2007 to January 2017. PATIENTS Study patients had fecal incontinence presented to a tertiary pelvic floor center. MAIN OUTCOME MEASURES Quality-of-life survey findings were measured. RESULTS A total of 946 patients with fecal incontinence were identified, and 656 (69.3%) had coexisting constipation. Patients with fecal incontinence with constipation were less likely to report a history of pregnancy (89.2% vs 91.4%; p = 0.001) or complicated delivery, such as requiring instrumentation (9.1% vs 18.1%; p = 0.005), when compared with patients with isolated fecal incontinence. Patients with fecal incontinence with constipation had higher rates of coexisting pelvic organ prolapse (Pelvic Organ Prolapse Inventory: 18.4 vs 8.2; p < 0.01), higher rates of urinary incontinence (Urinary Distress Inventory: 30.2 vs 23.4; p = 0.01), and higher pressure findings on manometry; intussusception on defecography was common. Patients with fecal incontinence with concurrent constipation had less severe incontinence scores at presentation (21.0 vs 23.8; p < 0.001) and yet lower overall health satisfaction (28.9% vs 42.5%; p < 0.001). Quality-of-life scores declined as constipation severity increased for lifestyle, coping, depression, and embarrassment. LIMITATIONS This was a single-institution study, and surgeon preference could bias population and anorectal physiology testing. CONCLUSIONS Patients with fecal incontinence with concurrent constipation represent a different disease phenotype and have different clinical and anorectal physiology test findings and worse overall quality of life. Treatment of these patients requires careful consideration of prolapse pathology with coordinated treatment of coexisting disorders. See Video Abstract at http://links.lww.com/DCR/A783.

Background and Aim Elderly, hospitalized patients suffer disproportionately from constipation; however, little data suggest that constipation prophylaxis reduces length of stay (LOS). We performed a retrospective analysis of elderly patients admitted to our hospital with congestive heart failure (CHF) to determine the effects of constipation prophylaxis on LOS. Methods Patients ≥ 65 years old admitted with the diagnosis of CHF in 2012 were evaluated for home and hospital laxative use on admission. Our primary outcome was LOS. We used linear regression modeling to independently evaluate the impact of constipation prophylaxis on LOS. Results Among 618 patients who were eligible for our study, 201 (32.5%) were using laxatives at home, whereas 254 (41.1%) were started on a prophylactic laxative on admission. There was no significant difference in LOS between patients receiving prophylaxis versus those who did not (P = 0.32). Patients with home laxative use had a 1 day longer LOS compared to those without laxative use (6 vs 5, P = 0.03). Among patients with home laxative use, there were 2 days longer LOS in those who were not given constipation prophylaxis on admission (8 vs 6, P = 0.002). After multivariate adjustment, failure to use constipation prophylaxis in patients with home laxative use was the only independent predictor of increased LOS (P = 0.03). Conclusions Among elderly patients admitted for CHF exacerbations, failure to use constipation prophylaxis in patients with home laxative use is associated with a significantly longer LOS. Our data suggest that routine use of bowel prophylaxis for elderly CHF patients with preexisting constipation may reduce LOS.

Patients are frequently advised to eliminate coffee, tea, and/or soda to reduce symptoms of gastroesophageal reflux (GER), such as heartburn or regurgitation. However, there are no data from prospective studies to support these recommendations.We collected data from the prospective Nurses' Health Study II from 48,308 women, 42-62 years old, who were free of regular GER symptoms, without cancer, and not taking proton pump inhibitors or H2 receptor agonists. Multivariate Cox proportional hazards models were used to assess associations between beverage intake and risk for GER symptoms.During 262,641 person-years of follow up, we identified 7961 women who reported symptoms of GER once or more per week. After multivariable adjustment, hazard ratios (HRs) for women with the highest intake of each beverage (more than 6 servings/day) compared to women with the lowest intake (0 servings/day) were 1.34 for coffee (95% CI, 1.13-1.59; Ptrend .0001), 1.26 for tea (95% CI, 1.03-1.55; Ptrend.001), and 1.29 for soda (95% CI, 1.05-1.58; Ptrend.0001). We obtained similar results when we stratified patients according to caffeine status. No association was observed between milk, water, or juice consumption and risk for GER symptoms. In a substitution analysis, replacement of 2 servings/day of coffee, tea, or soda with 2 servings of water was associated with reduced risk of GERD symptoms: coffee HR, 0.96 (95% CI, 0.92-1.00); tea HR, 0.96 (95% CI, 0.92-1.00); and soda HR, 0.92 (95% CI, 0.89- 0.96).In an analysis of data from the prospective Nurses' Health Study II, intake of coffee, tea, or soda was associated with an increased risk of GER symptoms. In contrast, consumption of water, juice, or milk was not associated with GER symptoms. Drinking water instead of coffee, tea, or soda reduced the risk of GER symptoms.

A subset of patients with functional defecation disorders have predominance of the puborectalis muscle (PRM) on three-dimensional high definition anorectal manometry (HDARM), known as paradoxical puborectalis syndrome (PPS). The aim of this study was to assess clinical and manometric differences between patients with and without PPS.A total of 227 women with functional defecation disorders undergoing HDARM between December 2012 and October 2016 at a single center were included in this study. All completed the Rome III constipation module and Pelvic Floor Distress Inventory 20 (PFDI-20).Eighty-seven out of 227 women had a 3D pressure topographic profile consistent with PPS. They had higher mean PDFI-20 scores for straining and incomplete evacuation symptoms than those without PPS. In addition, they demonstrated higher mean resting anal pressure, a more negative mean anorectal pressure differential, and a greater proportion with prolonged balloon expulsion test. These findings were more pronounced in a subgroup of 58 PPS patients with a distinct pattern of both posterior and posterolateral wall indentation.Among female patients with functional defecation disorders, those with PPS demonstrated clinical and manometric differences compared to those without PPS. These differences may be driven by predominant posterolateral wall indentation in a subgroup of PPS patients.

BACKGROUND: Ingestion of radiopaque markers (ROM) is frequently used to determine colonic transit in chronic constipation. Although ≥20% of retained markers at 5 days defines slow-transit constipation, some clinicians use the number of retained markers to determine disease severity. METHODS: We assembled a cross-sectional cohort of patients presenting for evaluation of chronic constipation who underwent transit testing by ROM and completed validated symptom severity and quality of life (QOL) measures. We performed a correlation analysis to determine whether there was an association between number of retained markers and symptom severity and QOL. KEY RESULTS: Among 159 patients undergoing evaluation for chronic constipation, there was poor correlation between the number of retained markers and symptom severity (R=0.09, P=0.25) and quality of life. Among the 55 patients with slow-transit constipation defined by ≥5 retained markers retained on Day 5, there were similarly poor correlations between symptom severity (R=0.17, P=0.21) and quality of life (R=0.07, P=0.60). Excluding patients with irritable bowel syndrome and outlet obstruction by balloon expulsion testing did not materially alter our results, nor did a multivariable analysis controlling for demographic and psychiatric confounders. CONCLUSIONS AND INFERENCES: Among patients with chronic constipation, number of retained markers on a ROM colonic transit study does not correlate with measures of symptom severity or QOL. Clinicians should be cautious about over-interpreting ROM transit testing.

BACKGROUND Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head-to-head studies comparing the clinical profile, constipation severity, impact on quality of life (QOL) and economic impact are lacking. METHODS We conducted a cross-sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease-specific QOL, somatization, and psychiatric comorbidities. We used multivariable linear regression to determine the predictors of QOL and number of healthcare visits. KEY RESULTS Sixty-six and 98 patients with CC were enrolled in the USA and India, respectively. Indian patients with CC had significantly more frequent bowel movements/week compared to their USA counterparts (Median 5 vs 3, P

Ingestion of radiopaque markers (ROMs) is a common means of assessing colonic transit time in chronic constipation. Because anorectal manometry (ARM) testing for pelvic floor dysfunction is mostly limited to academic centers, clinicians frequently use rectosigmoid accumulation of markers as a surrogate for pelvic floor dysfunction. We sought to determine whether rectosigmoid localization of markers on a ROM study correlated with measures of pelvic floor dysfunction by ARM and balloon expulsion testing.We assembled a multicenter, retrospective cohort of patients diagnosed with chronic constipation who underwent both transit testing by ROM transit testing and ARM with balloon expulsion testing. We compared the proportion of patients with outlet obstruction by rectoanal pressure gradient or prolonged balloon expulsion stratified by marker location.There were 610 patients with both ROM testing and ARM with balloon expulsion testing. The mean age was 44 years and 526 were women (86%). Eighty-one (13%) patients had markers confined to the rectosigmoid area alone and were compared with 529 patients with markers elsewhere (51%) or no retained markers (49%). Of those with markers confined to the rectosigmoid colon, 48 (59%) had a prolonged balloon expulsion compared with 276 (52%) who did not have rectosigmoid markers (P=0.28). The mean rectoanal gradient for patients with markers in the rectosigmoid colon was -29±46 mm Hg compared with -34±59 mm Hg for all others (P=0.59).Among patients with chronic constipation undergoing ROM transit testing, there is no association between rectosigmoid location of markers and rectoanal gradient or prolonged balloon expulsion.

Background Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. Methods/design ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma. Individuals (n = 180) will be randomized in a 1:1:1 ratio to low-dose (81 mg/day) or standard-dose (325 mg/day) aspirin or placebo. At two study visits, participants will provide lifestyle, dietary and biometric data in addition to urine, saliva and blood specimens. Stool, grossly normal colorectal mucosal biopsies and cytology brushings will be collected during a flexible sigmoidoscopy without bowel preparation. The study will examine the effect of aspirin on urinary prostaglandin metabolites (PGE-M; primary endpoint), plasma inflammatory markers (macrophage inhibitory cytokine-1 (MIC-1)), colonic expression of transcription factor binding (transcription factor 7-like 2 (TCF7L2)), colonocyte gene expression, including hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and those that encode Wnt signaling proteins, colonic cellular nanocytology and oral and gut microbial composition and function. Discussion Aspirin may prevent colorectal cancer through multiple, interrelated mechanisms. The ASPIRED trial will scrutinize these pathways and investigate putative mechanistically based risk-stratification biomarkers. Trial registration This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02394769. Registered on 16 March 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1744-z) contains supplementary material, which is available to authorized users.

GOALS We sought to determine the patient characteristics associated with increased absenteeism and Emergency Department (ED) utilization among patients with constipation. BACKGROUND Chronic constipation is associated with significant direct and indirect economic costs. There has been limited study of the predictors of direct and indirect costs in a population with refractory constipation. STUDY We conducted a cross-sectional cohort study of patients with chronic constipation who presented to a tertiary care center for anorectal manometry. We used standardized instruments to assess disease severity, quality of life, somatization, and psychiatric comorbidities. We used multivariable logistic regression to determine the predictors of work and school absenteeism as well as ED visits for constipation. RESULTS There were 148 consecutive patients enrolled (87% female, mean age 43) of whom 32 (21.6%) had high absenteeism and 36 (24.3%) visited the ED for constipation in the past year. Patients with high absenteeism and ED visits were more likely to be depressed (56.3% vs. 18.5%, P

BACKGROUND Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease frequently complicated by bowel symptoms. Multiple sclerosis typically first manifests with a demyelination event, also known as a clinically isolated syndrome (CIS). We sought to examine the prevalence of prodromal bowel symptoms predating a CIS in patients with MS as part of a recently characterized prodromal phase of disease. METHODS We constructed a retrospective cohort of MS patients with bowel symptoms and an identifiable CIS at two tertiary care centers over 14 years using administrative and billing data. We determined the date of onset of reported bowel symptoms in comparison with the date of first CIS and determined the overall prevalence of prediagnosis bowel symptoms within 1, 2, 3, and >3 years from a CIS. We used multivariable modeling to determine demographic and clinical risk factors for prediagnosis bowel symptoms. KEY RESULTS Among 385 MS patients with reported bowel symptoms, 122 (31.6%) reported bowel symptoms prior to CIS. The most common first bowel symptom was constipation (50.0%), followed by diarrhea (29.5%). The average lead time between a first bowel symptom and a CIS event was 3.7 ± 3.4 years. Pre-CIS fatigue (OR 4.48, 95% CI: 2.68-7.51, P

Background Higher body mass index (BMI) and low physical activity have been associated with increased prevalence of fecal incontinence (FI) in cross-sectional studies, but prospective studies examining the role of these factors are lacking. We sought to determine whether BMI and/or physical activity are associated with risk of FI among older women. Methods We prospectively examined the association between BMI and physical activity and risk of FI in the Nurses’ Health Study among 51,708 women who were free of FI in 2008. We defined FI as at ≥1 liquid or solid FI episode/month during the past year reported in 2010 or 2012. We used Cox proportional hazards models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for FI according to physical activity and BMI, adjusting for potential confounding factors. Results During more than 175,000 person-years of follow-up, we documented 5954 cases of incident FI. Compared with women in the lowest activity category (

Emerging evidence suggests a potential impact of gastrointestinal function on cardiometabolic risk. Abnormal bowel movements have been related to various cardiovascular risk factors such as dyslipidemia, hypertension, diabetes, and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects risk of cardiovascular disease (CVD) and mortality. In the Nurses’ Health Study, bowel movement frequency was self-reported in 1982 by 86,289 women free from CVD and cancer. During up to 30 years of follow-up, we documented 7,628 incident CVD cases and 21,084 deaths. After adjustment for dietary intake, lifestyle, medication use, and other risk factors, as compared with women with daily bowel movement, having bowel movements more than once daily was significantly associated with increased risk of CVD (hazard ratio [HR]: 1.13; 95% confidence interval [CI]: 1.05–1.21), total mortality (HR: 1.17; 95% CI: 1.12–1.22), and cardiovascular mortality (HR: 1.17; 95% CI: 1.07–1.28). With further adjustment for body mass index and diabetes status, the association with total mortality remained significant (HR: 1.10; 95% CI: 1.06–1.15), whereas the associations with incident CVD and cardiovascular mortality were no longer significant. Our results suggest increased bowel movement frequency is a potential risk factor for premature mortality.

The role of cannabinoids in gastrointestinal diseases is controversial and of great interest, yet their use in patients has not been critically examined. To determine the prevalence and effects of cannabis abuse on healthcare utilization, as measured by emergency department (ED) visits, in a large, tertiary gastroenterology practice. All patients seen in the gastroenterology clinic at a tertiary care center during a 27-year period (1986–2013) were included in our study to determine the overall prevalence of cannabis abuse. We matched cannabis abusers 1:2 with non-abusing controls to determine the effect of cannabis on ED utilization, our primary outcome. We used multivariate linear regression to adjust for confounders and define the independent effect of cannabis abuse on ED utilization. Our prevalence study cohort included 190,303 GI clinic patients with an overall cannabis abuse prevalence of 0.80 % (1520 patients). From 1986 to 2012, the prevalence of cannabis abuse in this clinic increased by 0.73 % (0.03 %/year) (p