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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.

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.

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Exclusion diets for gastrointestinal symptom management have been hypothesized to be a risk factor for avoidant/restrictive food intake disorder (ARFID; a non-body image-based eating disorder). In a retrospective study of pediatric and adult neurogastroenterology patients, we aimed to (1) identify the prevalence and characteristics of an exclusion diet history and (2) evaluate if an exclusion diet history was concurrently associated with the presence of ARFID symptoms.We conducted a chart review of 539 consecutive referrals (ages 6-90, 69% female) to adult (n = 410; January-December 2016) and pediatric (n = 129; January 2016-December 2018) neurogastroenterology clinics. Masked coders (n = 4) retrospectively applied DSM-5 criteria for ARFID and a separate coder assessed documentation of exclusion diet history. We excluded patients with no documentation of diet in the chart (n = 35) or who were not orally fed (n = 9).Of 495 patients included, 194 (39%) had an exclusion diet history, and 118 (24%) had symptoms of ARFID. Of reported diets, dairy-free was the most frequent (45%), followed by gluten-free (36%). Where documented, exclusion diets were self-initiated by patients/parents in 66% of cases, and recommended by gastroenterology providers in 30%. Exclusion diet history was significantly associated with the presence of ARFID symptoms (OR = 3.12[95% CI 1.92-5.14], p 0.001).History of following an exclusion diet was common and was most often patient-initiated among pediatric and adult neurogastroenterology patients. As patients with self-reported exclusion diet history were over three times as likely to have ARFID symptoms, providers should be cognizant of this potential association when considering dietary interventions.

Recent reports document avoidant/restrictive food intake disorder (ARFID) symptoms among 13-40% of adults presenting to neurogastroenterology clinics, but ARFID in pediatrics is understudied. We conducted a retrospective review of charts from 129 consecutive referrals (ages 6-18 years; 57% female) for pediatric neurogastroenterology examination, from January 2016 through December 2018. Eleven cases (8%) met the full criteria for ARFID by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis. Of patients with ARFID symptoms (n = 30), 20 (67%) cited fear of gastrointestinal symptoms as motivation for their avoidant/ restrictive eating. Compared to patients without ARFID symptoms, patients with ARFID symptoms were older (P .001), more likely to be female (51% vs 79%, P = 0.014), and more frequently presented with eating/weight-related complaints (15% vs 33%, P = 0.026). This pilot retrospective study showed ARFID symptoms present in 23% of pediatric neurogastroenterology patients; further research is needed to understand risk and maintenance factors of ARFID in the neurogastroenterology setting.

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.

Background Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. Methods This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. Results NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. Conclusions Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

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.

Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with disorders of gut-brain interaction (DGBI), but treatments for this population (DGBI + ARFID) have yet to be evaluated. We aimed to identify initial feasibility, acceptability, and clinical effects of an exposure-based cognitive-behavioral treatment (CBT) for adults with DGBI + ARFID.Patients (N = 14) received CBT as part of routine care in an outpatient gastroenterology clinic. A two-part investigation of the CBT included a retrospective evaluation of patients who were offered a flexible (8-10) session length and an observational prospective study of patients who were offered eight sessions. Feasibility benchmarks were ≥75% completion of sessions, quantitative measures (for treatment completers), and qualitative interviews. Acceptability was assessed with a benchmark of ≥70% patients reporting a posttreatment satisfaction scores ≥3 on 1-4 scale and with posttreatment qualitative interviews. Mixed model analysis explored signals of improvement in clinical outcomes.All feasibility and acceptability benchmarks were achieved (and qualitative feedback revealed high satisfaction with the treatment and outcomes). There were improvements in clinical outcomes across treatment (all p's .0001) with large effects for ARFID fear (-52%; Hedge's g = 1.5; 95% CI = 0.6, 2.5) and gastrointestinal-specific anxiety (-42%; Hedge's g = 1.0; 95% CI = 0.5, 16). Among those who needed to gain weight (n = 10), 94%-103% of expected weight gain goals were achieved.Initial development and testing of a brief 8-session CBT protocol for DGBI + ARFID showed high feasibility, acceptability, and promising clinical improvements. Findings will inform an NIH Stage 1B randomized control trial.While cognitive-behavioral treatments (CBTs) for ARFID have been created in outpatient feeding and eating disorder clinics, they have yet to be developed and refined for other clinic settings or populations. In line with the recommendations for behavioral treatment development, we conducted a two-part investigation of an exposure-based CBT for a patient population with high rates of ARFID-adults with disorders of gut-brain interaction (also known as functional gastrointestinal disorders). We found patients had high satisfaction with treatment and there were promising improvements for both gastrointestinal and ARFID outcomes. The refined treatment includes eight sessions delivered by a behavioral health care provider and the findings reported in this article will be studied next in an NIH Stage 1B randomized controlled trial.

Disruption of normal gastrointestinal (GI) function in critical illness is linked to increased morbidity and mortality, and GI dysmotility is frequently observed in patients who are critically ill. Despite its high prevalence, the diagnosis and management of GI motility problems in the intensive care unit remain very challenging, given that critically ill patients often cannot verbalize symptoms and the general lack of understanding of underlying pathophysiology. Common clinical presentations of GI dysmotility issues among critically ill patients include: (1) high gastric residual volumes, acid reflux, and vomiting, (2) abdominal distention, and (3) diarrhea. In this review, we discuss the differential diagnosis for intensive care unit patients with symptoms and signs concerning GI motility issues. There are many myths and longstanding misconceptions about the diagnosis and management of GI dysmotility in critical illness. Here, we uncover these myths and discuss relevant evidence in each subject area, with the goal of re-conceptualizing GI motility disorders in critical care and providing evidence-based recommendations for clinical care.

Little is known about the impact of psychiatric comorbidity on pharmacologic treatment outcomes, including neuromodulators (medications targeting the gut-brain axis), among adult patients with disorders of gut-brain interaction (DGBI). Accordingly, we aimed to examine associations between psychiatric comorbidity and DGBI pharmacologic treatment outcomes.In a retrospective study of consecutively referred new patients (N = 410; ages 18-90; 73% female) to a tertiary neurogastroenterology clinic in 2016 with follow-up through 2018, relationships between psychiatric illness (any psychiatric illness, anxiety disorders, depressive disorders) and pharmacologic treatment selection (any medication, neuromodulating medication) and treatment outcomes, respectively, were examined using multivariable logistic regression, adjusting for demographics, gastrointestinal (GI) diagnoses, and pre-existing neuromodulator use.Anxiety disorders (35%) were the most common psychiatric comorbidity, followed by depressive disorders (29%). Patients with anxiety disorders were more likely to be prescribed a neuromodulator by their gastroenterologist (OR = 1.72 [95% CI 1.10-2.75]) yet less likely to respond to neuromodulators (OR = 0.43 [0.21-0.90]) or any GI medication (OR = 0.24 [0.12-0.50]) in fully adjusted analyses. In contrast, depressive disorders were not associated with neuromodulator prescription or response.Anxiety disorders are common among patients with DGBI and significantly reduce the likelihood of GI pharmacologic treatment response to any medication prescribed, including neuromodulators.

Fecal incontinence (FI) is a debilitating gastrointestinal disorder with a devastating impact on quality of life

Introduction Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives. Methods We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used. Results With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio >$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-μg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life. Discussion Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.

Health care providers are likely to encounter patients with recurrent unexplained abdominal pain. Because hereditary angioedema (HAE) is a rare disease, it may not be part of the differential diagnosis, especially for patients who do not have concurrent skin swelling in addition to abdominal symptoms. Abdominal pain is very common in patients with HAE, occurring in up to 93% of patients, with recurrent abdominal pain reported in up to 80% of patients. In 49% of HAE attacks with abdominal symptoms, isolated abdominal pain was the only symptom. Other abdominal symptoms that commonly present in patients with HAE include distension, cramping, nausea, vomiting, and diarrhea. The average time from onset of symptoms to diagnosis is 6 to 23 years. Under-recognition of HAE in patients presenting with predominant gastrointestinal symptoms is a key factor contributing to the delay in diagnosis, increasing the likelihood of unnecessary or exploratory surgeries or procedures and the potential risk of related complications. HAE should be considered in the differential diagnosis for patients with unexplained abdominal pain, nausea, vomiting, and/or diarrhea who have complete resolution of symptoms between episodes. As highly effective targeted therapies for HAE exist, recognition and diagnosis of HAE in patients presenting with isolated abdominal pain may significantly improve morbidity and mortality for these individuals.

Colonic motility disorders may be influenced by the gut microbiota, which plays a role in modulating sensory and motor function. However, existing data are inconsistent, possibly due to complex disease pathophysiology, fluctuation in symptoms, and difficulty characterizing high-resolution taxonomic composition and function of the gut microbiome.Increasingly, human studies have reported associations between gut microbiome features and colonic motility disorders, such as irritable bowel syndrome and constipation. Several microbial metabolites have been identified as regulators of colonic motility in animal models. Modulation of the gut microbiota via dietary intervention, probiotics, and fecal microbiota transplant is a promising avenue for treatment for these diseases. An integration of longitudinal multi-omics data will facilitate further understanding of the causal effects of dysbiosis on disease. Further understanding of the microbiome-driven mechanisms underlying colonic motility disorders may be leveraged to develop personalized, microbiota-based approaches for disease prevention and treatment.

Satisfaction with current treatment options for irritable bowel syndrome with constipation (IBS-C) is low, with many patients turning to complementary treatments. Tai Chi is a mind-body medicine practice with proven efficacy in other functional disorders. As a proof-of-concept, we tested the feasibility and preliminary clinical outcomes associated with a Tai Chi program designed for IBS-C.A total of 27 IBS-C patients participated in a single-arm trial of 8 sessions of Tai Chi delivered weekly over 7 weeks via live videoconferencing in group format. Clinical improvement was assessed via change in IBS Symptom Severity Score (IBS-SSS) from baseline to 4 weeks posttreatment (week 11) with secondary outcomes exploring symptom ratings, IBS-related quality of life (IBS-QOL), GI-specific anxiety, abdominal distention, and psychological factors.Despite substantial dropout (n = 7; 26%), the treatment protocol had moderate to excellent feasibility for other criteria. Treatment satisfaction was excellent. Exit interviews confirmed high satisfaction with the program among completers, but a high burden of data collection was noted. One participant experienced an adverse event (mild, exacerbation of sciatica). There was a significant improvement in intra-individual IBS-SSS between baseline and posttreatment (average change -66.5, 95% CI -118.6 to -14.3, p = 0.01). Secondary outcomes were notable for improvements in other IBS symptom scoring measures, IBS-QOL, measured abdominal diameter, and leg strength.Our data provide preliminary evidence of the feasibility of a Tai Chi intervention for IBS-C, show promise for improving outcomes, and identify more streamlined data collection as an area for further program improvement.

Prescription drug costs exert profound effects on commercial insurance coverage and access to effective therapy. We aimed to assess threshold pricing to achieve budget neutrality of FDA-approved drugs treating irritable bowel syndrome from an insurance perspective, based on cost-savings resulting in decreased healthcare utilization through effective disease management. We constructed a decision-analytic model from an insurance perspective to assess the budget impact of IBS prescription drugs under usual insurance coverage levels in practice: (1) unrestricted drug access or (2) step therapy in a primary care population of middle-age, care-seeking IBS patients. Budget-neutral drug prices were then calculated which resulted in $0 budget impact to insurers with a short-term, one-year time horizon. If used according to FDA labeling, IBS-D drugs cost between $4778 and $16,844 per year and IBS-C drugs cost between $4319 and $4955 per year. These drug costs often exceed insurance expenditures of $6999 for IBS-D and $3929 for IBS-C if left untreated. Therefore, for drugs to have $0 budget impact to insurers, their prices would need to be discounted 36.7–74.2% for IBS-D drugs and 59.3–82.5% for IBS-C. IBS drugs are already priced to support step therapy “failing one of several common, inexpensive IBS treatments with a responder rate > 30–40%,” reflecting the subpopulation with more severe disease and greater healthcare costs. Broader prescription drug coverage for patients failing common, inexpensive IBS treatments to which at least 30–40% of patients would typically respond appears warranted to enable gastroenterologists to offer personalized approaches targeting specific mechanisms of this heterogeneous disease.

The majority of gastroparesis and functional dyspepsia cases (collectively, gastric neuromuscular dysfunction, or GND) remain idiopathic. It is believed that some idiopathic cases of GND may be triggered by an inflammatory insult to the gastrointestinal tract. We theorized that the profound foregut inflammation induced by pancreatitis could result in increased risk of GND.This was a case-control study of all patients undergoing gastric emptying scintigraphy between October 2017-2020 in an urban medical center with presumed GND. These were age-, sex-, and comparative health-matched to control patients with newly diagnosed microscopic colitis. Adjusted odds ratios were calculated using conditional logistic regression.Among the 650 patients with GND, 359 had gastroparesis, and 9.2% had a history of acute pancreatitis (vs 3.1% of controls). GND patients demonstrated increased odds of having a history of acute pancreatitis (adjusted odds ratio [aOR] 2.27, 95% confidence interval [CI] 1.33-4.03, P=.004) and recurrent pancreatitis (aOR 2.08, (95% CI 1.67-3.48, P=.002). Median time to GND diagnosis after first acute pancreatitis episode was 1,544 days (477.5, 3832). Patients with a history of pancreatitis associated GND had increased mortality vs. controls (aOR 3.41, 95% CI 0.96-5.48). Additionally, pancreatitis associated GND patients had more hospitalizations vs GND alone (13.8 vs 3.7, p.0001) during the study period.This is the first study demonstrating an independent association between pancreatitis and the risk of GND, which occurred ∼4.2 years after the first episode of acute pancreatitis. Pancreatitis should therefore be regarded as a possible risk factor for developing GND with important consequences for healthcare utilization.

Objective Little research exists on Rome IV disorders of gut-brain interaction (DGBI; formerly called functional gastrointestinal disorders) in outpatients with eating disorders (EDs). These data are particularly lacking for avoidant/restrictive food intake disorder (ARFID), which shares core features with DGBI. We aimed to identify the frequency and nature of DGBI symptoms among outpatients with EDs. Method Consecutively referred pediatric and adult patients diagnosed with an ED (n = 168, 71% female, ages 8-76 years) in our tertiary care ED program between March 2017 and July 2019 completed a modified Rome IV Questionnaire for DGBI and psychopathology measure battery. Results The majority (n = 122, 72%) of participants reported at least one bothersome gastrointestinal symptom. Sixty-six (39%) met criteria for a DBGI, most frequently functional dyspepsia-post-prandial distress syndrome subtype (31%). DGBI were surprisingly less frequent among patients with ARFID (30%) versus EDs that are associated with shape or weight concerns (45%; X2 [1] = 3.61, p = .058, Cramer's V = .147). Among those with ARFID, DGBI presence was associated with the fear of aversive consequences prototype and multiple comorbid prototype presence. Discussion We demonstrated notable overlap between DGBI and EDs, particularly post-prandial distress symptoms. Further research is needed to examine if gastrointestinal symptoms predict or are a result of greater ED pathology, including ARFID prototypes.

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.