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Kanika Sehgal,1 Hind J Fadel,2 Aaron J Tande,2 Darrell S Pardi,1 Sahil Khanna1 1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 2Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USACorrespondence: Sahil KhannaDivision of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USATel +1 507-266-4347Fax +1 507-293-3917Email Khanna.sahil@mayo.eduBackground: Coronavirus infectious disease 2019 (COVID-19) is primarily a respiratory disease. However, it may manifest with gastrointestinal symptoms that may overlap with Clostridioides difficile infection (CDI). COVID-19 appears to have higher mortality in those with comorbidities. We aimed to assess the outcomes of coinfection in these patients.Methods: A retrospective chart review was conducted to identify patients with CDI and COVID-19 from January 1st, 2020 to November 17th, 2020. Both infections were diagnosed via PCR. Clinical features, treatment for COVID-19 and CDI and outcomes including intensive care unit admission, colectomy, 30 day-mortality and long-term complications were analyzed.Results: Overall, 21 patients (20 hospitalized) with median age 70.9 years (range 51.8– 90.7 years) had CDI and COVID-19 within 4 weeks of each other. Of these, 4 patients (19%) with CDI were diagnosed with COVID-19 at the time of admission, 12 (57%) had CDI diagnosed after COVID-19, and 5 (23.9%) developed COVID-19 within 4 weeks after CDI. Fourteen patients (66.7%) were treated with medications directed against COVID-19 including remdesivir and dexamethasone (n=7), remdesivir with convalescent plasma (n= 1), remdesivir (n= 5) and dexamethasone (n=1). The most common treatment for CDI was oral vancomycin in 20 patients (95.2%), and 1 patient received intravenous metronidazole. No patient required colectomy for CDI but 2 (9.5%) required ICU admission. Four patients (19%) died likely due to COVID-19 with median age 80 years (range 61– 90 years).Conclusion: The relationship between COVID-19 and CDI is poorly understood, and studies are required to further investigate this association. Whether coinfection results in a worsening of outcomes, including mortality and clinical course, are questions that should be answered in future research studies. Diagnosing both infections for appropriate management is vital in light of overlapping symptoms.Keywords: diarrhea, infection, C. difficile, microbiome, antibiotics, COVID-19, mortality

Raseen Tariq,1,2 Dhruvika Mukhija,3 Arjun Gupta,4 Siddharth Singh,5 Darrell S Pardi,1 Sahil Khanna1 1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 2Department of Internal Medicine, Rochester General Hospital, Rochester, NY, 3Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, 4Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 5Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla, CA, USA Purpose: Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI.Patients and methods: We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle–Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model.Results: Eight studies (6 case–control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66–0.97; P=0.02). There was significant heterogeneity among the studies, with an I2 of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70–1.01; P=0.06, I2=75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61–0.99; P=0.04, I2=85%).Conclusion: Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders. Keywords: Clostridium difficile infection, incidence, meta-analysis, statins

Background: Colorectal cancer (CRC) screening in the United States is suboptimal. We conducted a national survey to learn about CRC screening perceptions and practices among trainees who perform CRC screening tests including those enrolled in Gastroenterology and Hepatology (GIH), General and Colorectal Surgery, and Diagnostic and Abdominal Radiology training programs.Methods: Program directors/administrators (PDs/PAs) from 642 programs were contacted by e-mail with an invitation to forward our survey to trainees in their programs. Participating trainees then completed an anonymous, Web-based questionnaire.Results: A total of 130/642 (20%) PDs/PAs forwarded our survey to their trainees, with responses received from 476 trainees (80 GIH, 261 surgery, 135 radiology). Colonoscopy was felt to be the best CRC screening test at reducing CRC mortality, with patient-related factors perceived as greater barriers than system-related factors. No single guideline was deemed very influential on CRC screening practices by most trainees. A total of 2 of 5 above-average risk patient profiles were not recognized by most trainees. Colonoscopy was selected as the preferred follow-up test for a positive CRC screening test by most trainees. However, 34% of respondents chose an option other than colonoscopy alone for follow-up of a positive fecal occult blood test.Conclusions: Based on data from this national survey of gastroenterology, surgery, and radiology trainees, opportunities exist for curricular changes that may help enhance current perceptions and practices of trainees who perform CRC screening tests. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening remains underutilized in the United States. We conducted a national survey of CRC screening education, prioritization, and self-perceived preparedness among resident physicians in Family Practice (FP), Internal Medicine (IM), and Obstetrics and Gynecology (OB/GYN) training programs.Methods: Directors/administrators from 1085 FP, IM, and OB/GYN training programs were contacted by e-mail with a request to forward an invitation to participate in our Web-based CRC screening education survey to all residents in their program. Willing residents submitted responses in anonymous fashion. Data were analyzed using chi2 tests and analysis of variance methods.Results: In total, 243 program directors/administrators forwarded our invitation, and 835 residents responded (384 FP, 266 IM, 177 OB/GYN, 8 undesignated specialty). Nearly all resident responders (89%) had received CRC screening education, but few content delivery methods were reported. Most felt at least somewhat comfortable or somewhat knowledgeable with respect to advising patients about CRC screening (90%), currently endorsed CRC screening guidelines (89%), and criteria used to identify familial CRC syndromes (50%). However, substantially fewer respondents reported feeling very comfortable or very knowledgeable in these areas (45%, 23%, and 5%, respectively). Program specialty, level of training, and gender were the strongest indicators of self-perceived preparedness.Conclusions: Although based on a relatively small sample of all FP, IM, and OB/GYN residents, these data suggest tangible opportunities to improve the CRC screening curriculum in primary care residency programs. [ABSTRACT FROM AUTHOR]

Microscopic colitis has 2 main subtypes, collagenous colitis and lymphocytic colitis, that are similar clinically and histologically and are distinguished mainly by the presence or absence of a thickened subepithelial collagen band. Microscopic colitis accounts for approximately 10% of chronic watery diarrhea and may be associated with abdominal pain and mild weight loss. It is typically diagnosed in the sixth to eighth decade of life, and there is a female pre-dominance that is more striking for collagenous colitis than for lymphocytic colitis. Endoscopic and radiographic findings of the colon appear normal. Diagnosis is made by colonic biopsy, which shows an intraepithelial lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. Many potential treatments have been reported, but few have been subjected to controlled treatment trials. A stepwise approach to therapy often leads to satisfactory control of symptoms. [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to assess the quality of bowel preparation in a matched cohort of patients actively using and not using GLP-1 RAs in a large health system in the United States., Methods: We performed a retrospective review of adult patients undergoing colonoscopy in 22 endoscopy units across 18 sites in the US., Results: Our cohort comprised 6235 patients (3344 cases and 2891 controls). Baseline variables causing suboptimal bowel preparation were setting of procedure (inpatient), sex (male), BMI (higher), T2D, IBD, opioid medications, heart failure, and cirrhosis. Total BBPS was significantly higher in controls even after controlling for the abovementioned variables (p < 0.01). Cases were significantly more likely to meet the definition of inadequate bowel preparation. There was no significant difference between different classes of GLP-1 RAs., Conclusions: Patients using GLP-1 RAs are more likely to have inadequate bowel preparation during colonoscopy, even accounting for other comorbidities., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Recurrent Clostridioides difficile infections (CDIs) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full-spectrum, oral microbiome therapeutic is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population., Methods: We conducted a multicenter, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by polymerase chain reaction or toxin enzyme immunoassay for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼6 × 10 11 colony-forming units of lyophilized microbial cells) or placebo after standard-of-care antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through week 8. Safety, efficacy, and microbiome endpoints were evaluated through weeks 8 and 24., Results: A total of 198 participants were analyzed: CP101 (n = 102) and placebo (n = 96). Overall, 27.5% had a first recurrence, and 62.7% were diagnosed by polymerase chain reaction-based testing. The proportion without CDI recurrence through week 8 was significantly higher in the CP101 group compared to the placebo group (74.5% [76 of 102] vs 61.5% [59 of 96], respectively; P = .0488), with durable efficacy observed through week 24 (73.5% [75 of 102] vs 59.4% [57 of 96], respectively; P = .0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to the placebo group. The incidence of adverse events was similar between the 2 groups., Conclusions: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. (ClinicalTrials.gov, Number NCT03110133)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI., Objective, Design, and Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities., Methods: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24., Results: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression., Conclusions: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients., Trial Registration: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141., (© 2024. The Author(s).)

Microscopic colitis is an inflammatory bowel disease that commonly presents with debilitating chronic watery diarrhea. Recent epidemiologic studies and randomized trials of therapeutics have improved the understanding of the disease. Medications, such as nonsteroidal anti-inflammatories, proton pump inhibitors, and antidepressants, have traditionally been considered as the main risk factors for microscopic colitis. However, recent studies have challenged this observation. Additionally, several epidemiologic studies have identified other risk factors for the disease including older age, female sex, smoking, alcohol use, immune-mediated diseases, and select gastrointestinal infections. The diagnosis of microscopic colitis requires histologic assessment of colon biopsies with findings including increased in intraepithelial lymphocytes with or without expansion of the subepithelial collagen band. The pathophysiology is poorly understood but is thought to be related to an aberrant immune response to the luminal microenvironment in genetically susceptible individuals. Antidiarrheal medications, such as loperamide or bismuth subsalicylate, may be sufficient in patients with mild symptoms. In patients with more severe symptoms, treatment with budesonide is recommended. Maintenance therapy is often necessary and several potential treatment strategies are available. Biologic and small molecule treatments seem to be effective in patients who have failed budesonide. There is an unmet need to further define the pathophysiology of microscopic colitis. Additionally, trials with novel therapies, particularly in patients with budesonide-refractory disease, are needed., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis., Aims: To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis., Methods: Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages., Results: A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I 2 =43% P =0.08], 57.8% [95% CI (0.3895; 0.7571), I 2 =0%, P =0.7541], and 39.3% [95% CI (0.0814; 0.7492), I 2 =66%, P =0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I 2 =67%, P =0.02], 45.3% [95% CI (0.1479; 0.7747), I 2 =0%, P =0.36] and 32.5% [95% CI (0.000; 0.8508), I 2 =53%, P =0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively., Conclusion: Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Microscopic colitis (MC) is an inflammatory condition of the large intestine. Primarily diagnosed in middle-aged and older adults, the incidence of the disease has increased markedly during the past few decades. While MC is associated with a reduced quality of life, large-scale studies on the association with future psychiatric disorders are lacking., Methods: We conducted a nationwide matched cohort study in Sweden from 2006 to 2021. Through a nationwide histopathology database (the Epidemiology Strengthened by histoPathology Reports in Sweden study), we identified 5,816 patients with a colorectal biopsy consistent with MC. These patients were matched with 21,509 reference individuals from the general population all of whom with no previous record of psychiatric disorders., Results: From 2006 to 2021, 519 patients with MC (median age 64.4 years [interquartile range = 49.5-73.3]) and 1,313 reference individuals were diagnosed with psychiatric disorders (9.9 vs 6.5 events per 1,000 person-years), corresponding to 1 extra case of psychiatric disorder in 29 patients with MC over 10 years. After adjustments, the hazard ratio for psychiatric disorders was 1.57 (95% confidence interval = 1.42-1.74). We found significantly elevated estimates up to 10 years after MC diagnosis and a trend toward higher risk with increasing age. Specifically, we observed increased risks for unipolar depression, anxiety disorders, stress-related disorders, substance abuse, and suicide attempts. In sibling-controlled analysis, the adjusted hazard ratio was 1.76 (95% confidence interval = 1.44-2.15)., Discussion: Patients with MC are at increased risk of incident psychiatric disorders compared with the general population., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings., Methods: A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic., Results: We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9)., Conclusions: Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Endoscopic retrograde cholangiopancreatography-guided transpapillary gallbladder drainage has emerged as an effective alternative for management of acute cholecystitis in nonoperable candidates. Delayed acute pancreatitis has not been previously described as an adverse event with this procedure. In this article, we describe 3 patients who developed acute pancreatitis between 2 and 6 weeks after stent insertion with no alternative inciting cause. Delayed acute pancreatitis may represent a rare and previously uncharacterized adverse event related to transpapillary gallbladder drainage., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Bile acid sequestrants (BAS) are an option for microscopic colitis (MC) refractory or intolerant to budesonide. There are inconsistent data on the prevalence of bile acid malabsorption (BAM) and utility of bile acid testing in MC. The aim of this systematic review and meta-analysis was to evaluate these outcomes., Methods: A systematic search of randomized control trials and observational studies of adults with MC treated with BAS was conducted using MEDLINE, Embase, Cochrane, and Scopus from inception to January 22, 2024. Data were extracted on (i) prevalence of BAM, (ii) clinical response and adverse events, and (iii) recurrence after BAS discontinuation. Data were pooled using random-effects models to determine weighted pooled estimates and 95% confidence intervals (CIs)., Results: We included 23 studies (1 randomized control trial, 22 observational), with 1,011 patients with MC assessed for BAM and 771 treated with BAS. The pooled prevalence of BAM was 34% (95% CI 0.26-0.42, I2 = 81%). The pooled response rate with BAS induction for all patients with MC, irrespective of BAM, was 62% (95% CI 0.55-0.70, I2 = 71%). There was a higher pooled response rate in patients with BAM compared with those without BAM ( P < 0.0001). The pooled rate of BAS-related adverse effects was 9% (95% CI 0.05-0.14, I2 = 58%)., Discussion: One-third of patients with MC had BAM, and almost two-thirds of all patients responded to BAS with limited side effects. Patients with MC and BAM were more likely to respond to therapy, supporting the value of bile acid testing., (Copyright © 2024 by The American College of Gastroenterology.)

Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected., (© 2024. The Author(s).)

Background and Aim: Although fidaxomicin is an effective first-line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease., Methods: This was a multicenter retrospective study of adults with inflammatory bowel disease and C. difficile infection treated with fidaxomicin with at least 3 months of follow up. The primary outcomes were treatment response, defined as resolution of C. difficile infection-attributed diarrhea and/or negative C. difficile infection stool test, and time to C. difficile infection recurrence after fidaxomicin., Results: Thirty-three patients (median age 42 years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C. difficile infection (26, 78.8%, median 2 episodes, range 0-15). Fidaxomicin led to resolution of C. difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55 days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution., Conclusions: In this cohort of patients with inflammatory bowel disease and C. difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response., Methods: Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 ± 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side effects). Logistic regression was used to identify predictors of response to BAS., Results: We identified 282 patients (median age, 59 years [range, 20-87 years]; 88.3% women) with median follow-up of 4.5 years (range, 0.4-9.1 years). Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (P = .98). The dose of BAS was not associated with response (P = .51). Bile acid testing was done in 31.9% of patients, and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 weeks (range, 1-172 weeks)., Conclusion: In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We performed an updated study to investigate the rates of urinary tract infections (UTIs) in patients with recurrent Clostridioides difficile infection (CDI) who received fecal microbiota transplantation (FMT) for CDI. We found a significant reduction in number of UTIs after FMT compared to patients who received antibiotics for CDI treatment. After FMT, we also observed a trend towards reduction of antibiotic resistance in organisms causing UTI., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears to be lower., Objectives: To perform an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs)., Design: A systematic review and meta-analysis was conducted., Data Sources and Methods: A systematic search of various databases was performed up to July 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose were included. We calculated weighted pooled rates (WPRs) with 95% confidence intervals (CIs)., Results: In all, 19 clinical trials with 1176 recurrent CDI patients were included. Of the patients treated with microbiota restoration, 897 experienced a clinical cure with a single microbiota restoration therapy (WPR, 78%; 95% CI, 71-85%). There was significant heterogeneity among studies with an I 2 of 88%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 373 of 523 patients (WPR, 72%; 95% CI, 60-82%) with microbiota restoration. Among the nine open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (WPR, 84%; 95% CI, 74-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR, 73 versus 84%, p  < 0.0001)., Conclusions: Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open-label studies were similar to observational studies., (© The Author(s), 2023.)

Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available., Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes., Design: Retrospective cohort study., Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996-February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p  < 0.05 was considered statistically significant., Results: Overall, 101 cases and 100 controls (1997-2018) were included; median age 27 (range, 20-41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% ( n  = 16), during pregnancy: 51.5% ( n  = 52), and postpartum: 32.7% ( n  = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery ( p  = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization ( p  = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19-543.19; p  = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04-0.99; p  = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes., Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment., Objectives: We aimed to assess histological changes over time., Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic., Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models., Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34-3.31, p  = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34-3.02, p  = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16-3.00, p  = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19-0.83, p  = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14-0.42, p  < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47-1.05, p  = 0.084)., Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Importance: The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown., Objective: To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial., Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history)., Interventions: Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days., Main Outcomes and Measures: The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic., Results: Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo)., Conclusions and Relevance: Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT03788434.

Background: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes., Methods: A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates., Results: Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2 =39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2 =73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2 =9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2 =56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2 =59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2 =63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2 =43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2 =23%)., Conclusions: FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence., Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks., Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry., Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI., Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population., Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%])., Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI., Trial Registration: ClinicalTrials.gov identifier: NCT03183141.

Background: Restorative proctocolectomy with IPAA is the procedure of choice when colectomy is needed for medically refractory ulcerative colitis. Pouchitis is one of the most common complications among patients who have undergone IPAA and represents a spectrum of disease varying in both phenotype and clinical course., Objective: This study aimed to assist clinicians and surgeons in the treatment of both acute and chronic pouchitis, including newer therapies and future directions., Diagnosis and Management: Diagnosis is made by endoscopy of the pouch with biopsy because other conditions may produce similar symptoms such as increased stool frequency, abdominal cramps, and urgency. Pouchitis is classified by duration (acute versus chronic), disease pattern (infrequent, relapsing, and continuous), and response to antibiotics (responsive, dependent, and refractory). The Pouchitis Disease Activity Index may be used to measure disease activity. The management of pouchitis is guided by the disease phenotype. Acute episodes are treated with an initial 2-week course of antibiotics (typically ciprofloxacin or metronidazole), although patients with relapsing or chronic pouchitis may require long-term antibiotic treatment or the cycling of different antibiotics. Certain probiotics may also be used for maintenance therapy in those with chronic symptoms. For patients with chronic antibiotic refractory pouchitis, oral budesonide, immunosuppressive agents (azathioprine), or biologic therapy (infliximab, adalimumab, vedolizumab, and ustekinumab) may be required for both induction and maintenance with close monitoring for potential side effects. In rare cases, diverting ileostomy or pouch excision may be required., Conclusion: Pouchitis represents a spectrum of disease phenotypes, ranging from acute antibiotic responsive pouchitis to chronic antibiotic refractory pouchitis. The management of pouchitis is primarily directed by the disease phenotype., (Copyright © The ASCRS 2022.)

Crohn's disease is a chronic gastrointestinal inflammatory disorder, characterized by episodes of relapsing and remitting flares. As the disease mechanism becomes better elucidated, there is a significant increase in the number of available biologic therapies. This article summarizes and synthesizes current Food and Drug Administration-approved biological therapy for Crohn's disease and examines the positioning of medical therapy as emerging biologics break onto the market., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise., Competing Interests: Declaration of interests CNB reports grants and personal fees from AbbVie, Janssen Canada, Pfizer, and Takeda Canada; and personal fees from Roche Canada, Bristol-Myers-Squibb Canada, Sandoz Canada, Mylan Pharmaceuticals, Takeda, and Medtronics Canada. DHB reports grants from Nextrast, Medtronic, and Takeda. WB reports consultant or speaker fees from Takeda, Braun, Johnson & Johnson, and Medtronic; and grants from VIFOR. RKC reports personal fees from AbbVie, Bristol Myers Squibb, Eli Lilly Janssen, Pfizer, Samsung Bioepis, and Takeda. SC reports personal fees from Pfizer and AbbVie. FAF reports personal fees from Arena, BMS, Braintree Labs, GI Reviewers, GSK, Innovation Pharmaceuticals, Iterative scopes, Janssen, Pfizer, and Sebela; and a data safety monitoring board role at Lilly and TheraVance. LAK reports personal fees from UpToDate and New Beta Innovation and grants from Varian Medical Systems. SE-H reports speaker fees from AbbVie, Bristol Myers Squibb, Janssen, Takeda, and Pfizer; and advisory board role at AbbVie, Prometheus, Bristol Myers, and UCB. SVK reports personal fees from Pfizer and grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring; and grants from Pfizer and Takeda. GSK reports consulting fees from Janssen, Bristol Meyers Squibb, United Healthcare, Spherix Health, and TechLab; and an editor role at UpToDate. JTM reports personal fees from Intuitive Surgical. XL reports personal fees AbbVie, Arrowhead Pharmaceuticals, and PathAI. UN reports grants and personal fees from Takeda, Janssen, and AbbVie; and personal fees from Pfizer. DSP reports research grants from Atlantic, Finch, Janssen, Pfizer, Seres, Takeda, Vedanta, and Applied Molecular Transport; and consulting fees from Vedanta, Seres, and Otsuka. JP reports speaker fees from AbbVie. DKR reports consulting fees from Olympus, Boston Scientific, Arles Pharmaceutical, Braintree Laboratories, Lumendi, Norgine, Endokey, and GU supplies; and research support from Olympus and Braintree Laboratories. DTR reports personal fees from AbbVie, Altrubio, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp–Syneos, Connect BioPharma, GalenPharma–Atlantica, Genentech–Roche, Gilead Sciences, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Lilly, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda, and TechLab. AS reports consulting fees from Takeda, Ethicon, Pfizer, and Oasis. BS reports personal fees from AbbVie, Janssen, and Takeda. ES reports grants and personal fees from AbbVie, Janssen, Takeda; and grants from Astra-Zeneca, Pfizer, and Genentech; and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, and Evidera. RAS reports personal fees from Merck & Co. WJS reports personal fees from AbbVie, Takeda, UCB, Janssen, Gilead, Pfizer, and Tract. WJS reports grants, personal fees, and stock or stock options from Prometheus Biosciences; grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, Glaxo Smith Kline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, and Theravance Biopharma; personal fees and stock or stock options from Beigene, Gossamer Bio, and Shoreline Bioscience; and personal fees from Allergan, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health (Salix), Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Glanmark Pharmaceuticals, Immunic (Vital Therapies), Incyte, Index Pharmaceuticals, Intact Therapeutics, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, and Thetis Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings., Competing Interests: ON, TS No competing interests declared, FF Research grant from Falk Pharma; Consulting fee from Tillotts and Biomedal; Lectures for General Electrics and Termo Fisher, and travel support from Tillotts, Ferring, and Janssen as listed in the ICMJE form, DP Grants from Atlantic, Finch, Salix, Janssen, Pfizer, Seres, Applied Molecular Transport, and Takeda; Consulting fees from Abbvie, Vedanta, Seres, Immunic, Merck, Otsuka, Ferring, Rise Therapeutics, Boehringer Ingelheim, and Summit Therapeutics as listed in the ICMJE form, (© 2022, Nielsen et al.)

Introduction: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known., Methods: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002-2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (&lt;50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years)., Results: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23-91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3-18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts., Discussion: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce., Aims: To compare clinical characteristics and treatment response by age at diagnosis., Methods: This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance., Results: We included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m 2 , P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07)., Conclusions: There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age., (© 2021. The Author(s).)

Background & Aims: Epidemiologic studies from Europe and North America have reported an increasing incidence of microscopic colitis (MC) in the late 20th century, followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade., Methods: Residents of Olmsted County, MN, diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011, and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses., Results: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19-90 y); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% CI, 22.7-28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4-18.2) and CC was 9.9 (95% CI, 8.1-11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (P < .01). There was no significant trend in age- and sex-adjusted incidence rate over the study period (P = .92). On December 31, 2019, the prevalence of MC, LC, and CC (including cases diagnosed before 2011) was 246.2, 146.1, and 100.1 per 100,000 persons, respectively., Conclusions: The incidence of MC and its subtypes was stable between 2011 and 2019, but its prevalence was higher than in previous periods. The incidence of MC continues to be associated with increasing age and female sex., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Vancomycin is the drug of choice for treating Clostridioides difficile infection (CDI). We compare CDI resolution with vancomycin taper, pulse, and taper-and-pulse regimens., Methods: We searched for Medline, Embase, Cochrane, and Scopus through October 9 th , 2020. Taper regimen was defined as dose reduction over time; pulse was a regimen less frequent than daily. Studies assessing CDI resolution rates were included. Meta-analyses for resolution rates were performed using weighted proportion ratios (WPR)., Results: Ten studies with 675 patients treated with vancomycin regimens were included. Resolution rates were 83% (212/266, 95% CI 69-94%, I 2   = 85%) for taper-and-pulse, 68% (264/383, 95% CI 57-78%, I 2  =  72%) for taper alone, and 54% (11/26 95% CI 0-100%, I 2  =  86%) for pulse alone regimens. Taper-and-pulse was superior to taper alone (WPR 83% vs 68%, p < 0.0001) and pulse alone (WPR 83% vs 54%, p < 0.0004), no significant difference between taper alone or pulse alone (WPR 68% vs 54%, p = 0.1)., Conclusions: Limitations of our analysis are a small number of included studies and heterogeneity. Vancomycin taper-and-pulse seems superior to pulse alone or taper alone for recurrent CDI. A randomized controlled trial comparing vancomycin taper-and-pulse to fidaxomicin and microbiome restoration is needed.

Microscopic colitis (MC) is a common cause of chronic watery diarrhea, with the highest incidence in women over age 50. 1 Cross-sectional studies have suggested that patients with MC have a lower incidence of adenomatous colon polyps compared with those without MC. 2-4 The existing literature is limited by cross-sectional design, small sample sizes, lack of longitudinal follow-up, and the use of average-risk patients, rather than those with chronic diarrhea, as controls. We aimed to explore the association between MC and colon adenomas., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC., Methods: A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response., Results: Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment., Conclusions: MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Objectives: Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment., Materials and Methods: This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities., Results: 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy ( p = .029) and budesonide therapy long-term ( p = .0028). Budesonide therapy long-term ( p = .047) was associated with radiographic abnormalities in multivariate analysis., Conclusions: Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches., Competing Interests: Declaration of interests BA reports a research grant from Takeda and personal fees from Janssen, AbbVie, Pfizer, Samsung Biospis, Ferring, Bristol Myers Squibb. CNB reports grants and personal fees from AbbVie, Janssen, Pfizer, and Takeda, personal fees from Amgen, Bristol Myers Squibb, Roche, Sandoz, and Mylan Pharmaceuticals, and speaker fees from Medtronics. DHB reports grants from Medtronic and Takeda. RKC reports personal fees from AbbVie, Janssen, Samsung Bioepis, and Birstol Myers Squibb. FAF reports serving as an advisory board member for Bristol Myers Squibb, Braintree Labs, Gilead, GSK, Iterative Scopes, Janssen, Pfizer, and Sebela; owns stocks and shares in Innovation Pharmaceuticals; and is a member of Data Safety and Monitoring Boards for Lilly and Theravance. SVK reports grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring, and grants from Pfizer and Takeda. JTM reports personal fees from Intuitive Surgical. UN reports grants and personal fees from Takeda, Janssen, and AbbVie, and personal fees from Pfizer. SE-H reports personal fees from AbbVie, Janssen, Takeda, UCB–Ferring, Pfizer, Bristol Myers Squibb, and Prometheus. JPh reports speaker fees from AbbVie. DTR reports personal fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, CDx Diagnostics, Celgene/Syneos, Check-Cap, Dizal Pharmaceuticals, Galen Pharma/Atlantica, Genentech/Roche, Ichnos Sciences SA, InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Marrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Takeda, and TechLab. WJS reports grants, personal fees, and stock options from Prometheus Biosciences; grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer-Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, and Theravance Biopharma; personal fees and stock options from Beigene, Gossamer Bio, Shoreline Bioscience, and personal fees from Allergan, AbbVie, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health, Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Gilead, Glanmark Pharmaceuticals, Immunic, Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Pfizer, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Thetis Pharmaceuticals, Tract, and UCB. ES reports grants and personal fees from AbbVie, Janssen, and Takeda, grants from AstraZeneca, Pfizer, and Genentech, and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, and Evidera. JSe reports speaker fees from Janssen and Takeda. DAS reports personal fees from AbbVie, Takeda, UCB, Jansen, Gilead, Pfizer, and Tract. SV reports consultancy fees and/or speaking fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, Merck Sharpe & Dohme, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, and Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown., Methods: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied., Results: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery., Discussion: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI., Methods: We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure., Results: Overall, 460 patients were included (median age, 57 years [18-94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%-84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15-.49; P < .001)., Conclusions: The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiota-restoring therapies are needed, particularly standardized, easy-to-administer formulations., Methods: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses self-administered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants' microbiome composition was assessed prior to and for 6 months after treatment., Results: Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrence-free at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants' microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders' microbiomes showed increased Bacteroidia and Clostridia., Conclusions: Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders' microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation., Clinical Trials Registration: NCT02981316., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner., Competing Interests: Declaration of interests BA reports a research grant from Takeda and personal fees from Janssen, AbbVie, Pfizer, Samsung Biospis, Ferring, Bristol Myers Squibb. CNB reports grants and personal fees from AbbVie, Janssen, Pfizer, and Takeda, personal fees from Amgen, Bristol Myers Squibb, Roche, Sandoz, and Mylan Pharmaceuticals, and speaker fees from Medtronics. DHB reports grants from Medtronic and Takeda. RKC reports personal fees from AbbVie, Janssen, Samsung Bioepis, and Birstol Myers Squibb. SVK reports grants from Gilead Sciences and TechLab. PGK reports personal fees from AbbVie, Janssen, Pfizer, Takeda, and Ferring, and grants from Pfizer and Takeda. JTM reports personal fees from Surgical. UN reports grants and personal fees from Takeda, Janssen, and AbbVie, and personal fees from Pfizer. SE-H reports personal fees from Abbvie, Janssen, Takeda, UCB–Ferring, Pfizer, Bristol Myers Squibb, and Prometheus. JP reports speaker fees from AbbVie. DTR reports personal fees from AbbVie, Abgenomics, Allergan, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, CDx Diagnostics, Celgene–Syneors, Check-Cap, Dizal Pharmaceuticals GalenPharma–Atlantica, Genentech–Roche, Ichnos Sciences SA, InDex Pharmaceuticals, Iterative Scopes, Janssen, Lilly, Materia Prima, Marrow River Mgmt, Pfizer, Prometheus Laboratories, Reistone, Takeda, and TechLab. WJS reports grants, personal fees, and stock options from Prometheus Biosciences, grants and personal fees from AbbVie, Abivax, Alimentiv, Arena Pharmaceuticals, Boehringer–Ingelheim, Celgene, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Surrozen, Takeda, Theravance Biopharma, personal fees and stock options from Beigene, Gossamer Bio, Shoreline Bioscience, and personal fees from Allergan, AbbVie, Amgen, Applied Molecular Transport, Avexegen Therapeutics, Bausch Health, Beigene, Bellatrix Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Celltrion, Cellularity, Conatus, Cosmo Pharmaceuticals, Escalier Biosciences, Ferring, Forbion, Equillium, Gilead, Glanmark Pharmaceuticals, Immunic, Incyte, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyowa Kirin Pharmaceutical Research, Kyverna Therapeutics, Landos Biopharma, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Pfizer, Progenity, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Ritter Pharmaceuticals, Shanghai Pharma Biotherapeutics, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Thetis Pharmaceuticals, Tract, and UCB. ES reports grants and personal fees from AbbVie, Janssen, and Takeda, grants from AstraZeneca, Pfizer, and Genentech, and personal fees from Seres Health, Protagonist Therapeutics, Celgene, Entera Health, Bristol Myers Squibb, Evidera. SV reports consultancy fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, Hospira, Janssen, Mundipharma, Merck Sharpe & Dohme, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance, Tillots Pharma AG, and grants from AbbVie, Johnson & Johnson, Pfizer, and Takeda. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)