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Brandon M Shore,1 Bharati Kochar,2,3 Hans H Herfarth,4,5 Edward L Barnes4,5 1Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; 3The Mongan Institute, Boston, MA, USA; 4Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Center for Gastrointestinal Biology and Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACorrespondence: Edward L Barnes, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Campus Box #7080, 130 Mason Farm Road, Chapel Hill, NC, 27599-7080, USA, Tel +1 919-962-3112, Fax +1 919-966-6842, Email edward_barnes@med.unc.eduAbstract: The population of older patients with inflammatory bowel disease (IBD) is expected to continue to increase in the coming decades, which necessitates and improved understanding of the critical issues faced by patients in this population. Although restorative proctocolectomy with IPAA remains the surgical procedure of choice for the majority of patients with medically refractory ulcerative colitis (UC) and UC-related dysplasia, the evidence surrounding surgery for older patients UC remains sparse. In particular, comparisons of outcomes among older and younger patients undergoing IPAA and comparisons between older patients undergoing IPAA and those undergoing proctocolectomy with end ileostomy remain an understudied and important issue, as evidence in this area will be used to guide patient-centered surgical choices among older patients who require colectomy for UC. In this narrative review, we review the available literature regarding IPAA for older patients, as well as the pre-, peri-, and postoperative factors that may influence outcomes in this population.Keywords: pouchitis, surgery, older age, ulcerative colitis, J-pouch

Competing Interests: Declarations. Conflicts of interest: Edward L. Barnes has served as a consultant for AbbVie, Bristol-Meyers Squibb, Pfizer, Eli Lilly, Boomerang, Direct Biologics, and Target RWE. Millie D. Long has served as a consultant for AbbVie, Pfizer, Takeda, Lilly, Bristol-Meyers Squibb, Target RWE, and Prometheus and has received research support from Pfizer, Takeda and Janssen. Hans H. Herfarth has served as a consultant for Alivio, AMAG, BMS, Boehringer, ExeGi Pharma, Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres and research support from Allakos, Artizan, NovoNordisk, Pfizer Sarah McGill receives research support from: Revivicor, EvoEndo, Exact Sciences, Guardant Health, Clinical Genomics, Finch Therapeutics and Freenome Holdings. Alicia Muratore has no relevant disclosures for this work.

Objectives: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data., Methods: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs. combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development., Results: A trend towards increased treatment failure among HLA DQA1*05 positive participants was not significant (HR 1.58, 95% CI 0.95-2.62; p=0.08). After stratification by HLA DQA1*05 and by methotrexate vs. placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05 positive patients on placebo (HR 0.31, 95% CI 0.13-0.70; p=0.005).A trend toward increased ADA development among HLA DQA1*05 positive participants was not significant (odds ratio [OR] 1.96, 95% CI 0.90-4.31, p=0.09). After further stratification, HLA DQA1*05 negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05 positive patients on placebo (OR 0.12, 95% CI 0.03-0.55; p=0.008)., Conclusions: In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab)., Methods: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization., Results: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14)., Conclusions: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation., (© The Author(s) 2024. 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.)

Background: The value of histologic assessment after ileal pouch-anal anastomosis (IPAA) has not been definitively determined. We evaluated the correlation between histology and endoscopic findings, as well as the proportion of patients with inflammation in areas beyond the pouch body on their initial pouchoscopy after IPAA., Methods: In a retrospective cohort study, we evaluated patients who underwent IPAA for UC between 2012 and 2020 and subsequently underwent a pouchoscopy with routine biopsies of the pouch body, pre-pouch ileum, and rectal cuff. We compared endoscopic and histologic assessments in each location using χ2 testing and Spearman correlation, as well as the development of pouchitis and Crohn's-like disease of the pouch (CLDP) in longitudinal follow-up., Results: Among 126 patients, the median time to pouchoscopy after IPAA was 384 days, with 82 patients (65%) having inflammation of the pouch body. Significantly more patients with pouch body inflammation had histologic inflammation compared with patients without pouch body inflammation (96% vs 22%, P < .001, r = 0.769). Additionally, 16 patients (13%) were found to have endoscopic inflammation of the pre-pouch ileum with corresponding histologic inflammation in 88%; of these, 31% later developed CLDP. In contrast, 13% of patients with no endoscopic inflammation displayed histologic inflammation, with none later developing CLDP. Forty-six percent of patients had rectal cuff inflammation (correlation with histologic inflammation r = 0.580)., Conclusions: In our evaluation, the added benefit of histology in the presence of visible endoscopic inflammation for disease activity assessment scores is unclear. The prognostic value of histologic inflammation without endoscopic inflammation warrants a longitudinal study., (© The Author(s) 2024. 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.)

Background & Aims: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC); however, clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis., Methods: We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC from 1996-2020. We used Cox proportional hazard modeling to assess the impact of antibiotic, nonsteroidal anti-inflammatory drug (NSAID) exposure, and appendectomy on diagnosis of acute pouchitis in the first 2 years after IPAA surgery., Results: Among 1616 eligible patients, 46% developed pouchitis in the first 2 years after IPAA. Antibiotic exposure in the 12 months before IPAA was associated with an increased risk of pouchitis (adjusted hazard ratio [aHR], 1.41; 95% confidence interval [CI], 1.22-1.64) after adjusting for anti-tumor necrosis factor alpha use and sex. Compared with persons without any antibiotic prescriptions in the 12 months before IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR, 1.30; 95% CI, 1.11-1.52) and 3 or more courses (aHR, 1.77; 95% CI, 1.41-2.21). NSAID exposure in the 12 months before IPAA and appendectomy were not associated with risk of acute pouchitis (P = .201 and P = .865, respectively)., Conclusions: In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months before IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Our understanding of outcomes after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is largely based on analyses of selected populations. We created a state-level registry to evaluate the epidemiology of IPAA surgery and pouch-related outcomes across the major healthcare systems performing these surgeries in our state., Methods: We created a retrospective cohort of all patients undergoing restorative proctocolectomy with IPAA for UC at 1 of 4 centers between January 1, 2018, and December 31, 2020. The primary outcomes of this study were the rate of complications and all-cause readmissions within the first 30 days of the final stage of IPAA surgery., Results: During the study period, 177 patients underwent IPAA surgery with 66 (37%) experiencing a complication within 30 days. After adjusting for the number of stages in IPAA surgery, patients with extensive UC (odds ratio, 3.61; 95% confidence interval, 1.39-9.33) and current or former smokers (odds ratio, 2.98; 95% confidence interval, 1.38-6.45) were more likely to experience a complication. Among all patients, 57 (32%) required readmission within 30 days. The most common reasons for readmission were ileus/small bowel obstruction (22%), peripouch abscess (19%), and dehydration (16%)., Conclusion: In this first state-level examination of the epidemiology of IPAA for UC, we demonstrated that the complication rate after IPAA for UC was 37%, with one-third of patients being readmitted within 30 days. Extensive disease at the time of colectomy appears to be an indicator of more severe disease and may portend a worse prognosis after IPAA., (© 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.)

Background: IPAA is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of IPAA within individual states but not at the national level in the United States., Objective: This study aimed to assess the rate of IPAA after total colectomy for ulcerative colitis in a national population and identify factors associated with IPAA., Design: This was a retrospective cohort study., Settings: This study was performed in the United States., Patients: Patients who were aged 18 years or older and who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients older than 65 years with Medicare., Main Outcome Measures: The primary outcome was IPAA. Multivariable logistic regression was used to assess the association between covariates and the likelihood of undergoing IPAA., Results: In total, 2816 patients were included, of whom 1414 (50.2%) underwent IPAA, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with IPAA but socioeconomic status was not., Limitations: This retrospective study included only patients with commercial insurance., Conclusions: A total of 50.2% of patients who had total colectomy for ulcerative colitis underwent IPAA, and younger age, lower comorbidities, and elective cases are associated with a higher rate of IPAA placement. This study emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract ., Factores Asociados Con La Realizacin De Anastomosis Analbolsa Ileal Despus De Una Colectoma Total Por Colitis Ulcerosa: ANTECEDENTES:La anastomosis ileo-anal se considera el procedimiento de elección para la cirugía reparadora tras la colectomía total por colitis ulcerosa. Estudios previos han examinado la tasa de anastomosis ileo-anal dentro de los estados individuales, pero no a nivel nacional en los Estados Unidos.OBJETIVO:Evaluar la tasa de anastomosis bolsa ileal-anal después de la colectomía total para la colitis ulcerosa en una población nacional e identificar los factores asociados con la anastomosis bolsa ileal-anal.DISEÑO:Se trata de un estudio de cohortes retrospectivo.LUGAR:Este estudio se realizó en los Estados Unidos.PACIENTES:Los pacientes que tenían ≥18 años de edad que se sometieron a colectomía total entre 2009 y 2019 para un diagnóstico de colitis ulcerosa fueron identificados dentro de una base de datos comercial. Esta base de datos excluyó a los pacientes con seguro público, incluidos todos los pacientes >65 años con Medicare.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la anastomosis ileal bolsa-anal. Se utilizó una regresión logística multivariable para evaluar la asociación entre las covariables y la probabilidad de someterse a una anastomosis ileal.RESULTADOS:En total, se incluyeron 2.816 pacientes, de los cuales 1.414 (50,2%) se sometieron a anastomosis ileo-anal, 928 (33,0%) no se sometieron a ninguna otra intervención quirúrgica y 474 (16,8%) se sometieron a proctectomía con ileostomía terminal. La edad más joven, las comorbilidades más bajas, el caso electivo, y el abordaje laparoscópico en la colectomía inicial se asociaron significativamente con la anastomosis ileal bolsa-anal, pero no el estatus socioeconómico.LIMITACIONES:Este estudio retrospectivo incluyó sólo pacientes con seguro comercial.CONCLUSIONES:Un 50,2% de los pacientes se someten a anastomosis ileo-anal y la edad más joven, las comorbilidades más bajas y los casos electivos se asocian con una mayor tasa de colocación de anastomosis ileo-anal. Esto subraya la importancia de asegurar el seguimiento con cirujanos colorrectales para ofrecer la opción de cirugía reparadora, especialmente en pacientes sometidos a colectomías urgentes o emergentes. (Traducción-Dr. Yolanda Colorado )., (Copyright © The ASCRS 2024.)

Introduction: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy., Methods: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52., Results: Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib., Discussion: Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch., Methods: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch., Results: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status., Discussion: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Our understanding of the epidemiology of inflammatory conditions of the pouch and effectiveness of treatment is largely based on selected populations. We created a state-level registry to evaluate the incidence of pouchitis and the effectiveness of treatments used in an initial episode of pouchitis., Methods: In a state-level retrospective cohort of all patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis between January 1, 2018, and December 31, 2020, we evaluated the incidence of pouchitis and compared the proportion of patients developing recurrent pouchitis and chronic antibiotic-dependent pouchitis according to initial antibiotic therapy., Results: A total of 177 patients underwent surgery with 49 (28%) developing pouchitis within the 12 months after the final stage of IPAA. Patients with extraintestinal manifestations of inflammatory bowel disease (IBD) were significantly more likely to develop pouchitis within the first 12 months after IPAA (adjusted odds ratio 2.45, 95% confidence interval 1.03-5.81) after adjusting for family history of IBD (adjusted odds ratio 3.50, 95% 1.50-8.18). When comparing the proportion of patients who developed recurrent pouchitis or chronic antibiotic-dependent pouchitis with those who experienced an isolated episode of pouchitis, there were no significant differences among the initial antibiotic regimens used., Discussion: In a state-level examination of outcomes after IPAA for ulcerative colitis, patients with extraintestinal manifestations of IBD were more likely to develop pouchitis; however, the initial antibiotic regimen chosen did not seem to affect long-term outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Anastomotic strictures occur in up to 38% of patients after ileal pouch-anal anastomosis (IPAA). We sought to compare the safety, effectiveness, and durability of mechanical dilation using a Hegar dilator to endoscopic through-the-scope balloon dilation (EBD) among IPAA patients with a rectal or ileoanal anastomotic stricture., Methods: We identified adult patients with an IPAA for ulcerative colitis (UC) who underwent a pouchoscopy between January 1, 2015, and December 31, 2019, at a single institution. We compared the effectiveness (median maximum diameter of dilation [MMD]), safety, and durability of mechanical and balloon dilation using standard statistical comparisons., Results: A total 74 patients had a stricture at the ileoanal anastomosis and underwent at least 1 mechanical or balloon dilation. The MMD with mechanical dilation was 19 (interquartile range [IQR], 18-20) mm for the first dilation and 20 (IQR, 18-20) mm for the second and third dilations. With balloon dilation, the MMD was 12 (IQR, 12-18) mm for the first dilation, 15 (IQR, 12-16.5) mm for the second dilation, and 18 (IQR, 15-18.5) mm for the third dilation. Patients undergoing mechanical dilation experienced a longer duration to second dilation (median 191 days vs 53 days: P < .001), with no difference in complications such as bleeding or perforation noted., Conclusions: Among patients with ileoanal and rectal strictures, mechanical and balloon approaches to dilation demonstrated similar safety profiles and effectiveness. Mechanical dilation with Hegar dilators appears to be an effective and safe approach to the treatment of distal strictures after IPAA., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of Interest: This author discloses the following: Hans H. Herfarth has served as a consultant for: Alivio, AMAG, Bristol Myers Squibb, Boehringer, ExeGI, Finch, Fresenius Kabi, Galapagos, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres, Ventyx and research support from Artizan Biosciences, Allakos, NovoNordisk, and Pfizer. The remaining authors disclose no conflicts.

Background: Antibiotics are a cornerstone in management of intra-abdominal abscesses in Crohn's disease (CD). Yet, the optimal route of antibiotic administration is poorly studied. We aimed to compare surgical and nonsurgical readmission outcomes for patients hospitalized for intra-abdominal abscesses from CD discharged on oral (PO) or intravenous (IV) antibiotics., Methods: Data for patients with CD hospitalized for an intra-abdominal abscess were obtained from 3 institutions from January 2010 to December 2020. Baseline patient characteristics were obtained. Primary outcomes of interest included need for surgery and hospital readmission within 1 year from hospital discharge. We used multivariable logistic regression models and Cox regression analysis to adjust for abscess size, history of prior surgery, history of penetrating disease, and age., Results: We identified 99 patients discharged on antibiotics (PO = 74, IV = 25). Readmissions related to CD at 12 months were less likely in the IV group (40% vs 77% PO, P = .01), with the IV group demonstrating a decreased risk for nonsurgical readmissions over time (hazard ratio, 0.376; 95% confidence interval, 0.176-0.802). Requirement for surgery was similar between the groups. There were no differences in time to surgery between groups., Conclusions: In this retrospective, multicenter cohort of CD patients with intra-abdominal abscess, surgical outcomes were similar between patients receiving PO vs IV antibiotics at discharge. Patients treated with IV antibiotics demonstrated a decreased risk for nonsurgical readmission. Further prospective trials are needed to better delineate optimal route of antibiotic administration in patients with penetrating CD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Patients with medically refractory ulcerative colitis who previously would have undergone surgery can now elect for subsequent medical therapy., Methods: In a commercially insured population, we evaluated the proportion of patients initiating second-line, third-line, or fourth-line treatment who underwent colectomy in the following 12 months., Results: Among 3,325 patients with ulcerative colitis, the colectomy rate within 12 months of a switch in therapy increased from 12% with the first switch to 17% and 19% with the second and third switches, respectively ( P < 0.001)., Discussion: Treatment effectiveness declines with successive switching; however, even after initiating fourth-line therapy, most patients remain surgery-free., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited., Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals., Results: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations., Conclusions: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population., Competing Interests: E.L.B. has served as a consultant for AbbVie, Bristol-Meyers Squibb, Eli Lilly, and Target RWE. P.D. has served as a consultant or on an advisory board for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, Arena Pharmaceuticals, Takeda Pharmaceuticals LLC, Roche Genentech, Bristol Myers Squibb and Scipher Medicine Corporation. He has also received funding under a sponsored research agreement unrelated to the data in the paper from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb-Celgene, Janssen, Landos Pharma, Teva Pharma, Iterative scopes, CorEvitas and Boehringer Ingelheim. P.D. holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. P.B.-P. has received honorarium from the Takeda speaker’s bureau. L.R. has served on an advisory board for Janssen. LR holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. M.D. has served as a consultant or has received advisory board fees from Abbvie, Arena, BMS, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Labs, Takeda. She has received grant support from Janssen, Abbvie. She also has the following relationships: Licenser of software: Takeda; Co-Founder, Equity ownership and board of director for Trellus Health Shannon Chang has served as a consultant for AbbVie, BMS, and Pfizer. R.K.C. has participated in advisory boards for AbbVie, Bristol Myers Squibb, Fresenius Kabi, and has served as a consultant for Fzata, Magellan Health, Pfizer, and Samsung Bioepis. He is on the Data Safety Monitoring Board for Adiso, is a member of the Executive Committee for the IBD Education Group and is Co-Director of the CorEvitas Registry. M.D.L. has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, Target Pharmasolutions and has received research support from Pfizer and Takeda. H.H.H. has served as a consultant for Alivio, AMAG, BMS, ExeGI Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres and has received research support from Pfizer and Artizan Biosciences. M.K., P.D.R.H., J.B., and C.A. have no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy., Methods: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected., Results: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs., Conclusions: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile., Clinicaltrials: gov, Number: NCT02772965., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)., Aims: We aimed to investigate the relationship between acute pouchitis within 180 days of the final stage of IPAA surgery (very early pouchitis) and the future development of chronic antibiotic dependent pouchitis (CADP) and Crohn's-like disease of the pouch (CLDP)., Methods: We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between very early pouchitis and the development of CADP and CLDP., Results: Among 626 patients undergoing IPAA for UC, 137 (22%) developed very early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed CLDP in a median follow-up of 5.18 years (interquartile range 0.94-10.8 years). Very early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR3.65, 95% CI 2.19-6.10) as was primary sclerosing cholangitis (aOR 3.97, 95% CI 1.44-11.0). Very early pouchitis was associated with increased odds for developing CLDP (aOR 2.77, 95% CI 1.54-4.98) along with a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96)., Conclusion: In this cohort, very early pouchitis was associated with an increased risk of developing CADP and CLDP. These findings highlight very early pouchitis as a unique risk factor for chronic inflammatory conditions of the pouch and the need for future studies evaluating potential strategies for secondary prophylaxis strategies in this population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recurrent or chronic antibiotic therapy is a therapeutic hallmark of chronic antibiotic-dependent pouchitis (CADP) or Crohn's-like disease of the pouch. Antibiotics alter the gut microbiome, which may increase the risk of Clostridioides difficile infection (CDI). The aim of this study was to determine the prevalence of CDI in patients with CADP and Crohn's-like disease of the pouch., Methods: We conducted a retrospective cohort study of patients with CADP or Crohn's-like disease of the pouch at a tertiary academic medical center. The primary outcome was prevalence of CDI. Secondary outcomes included antibiotic therapy at the time of CDI diagnosis, treatment regimens for CDI, and subsequent outcomes., Results: Overall, 18 of 198 (9.1%) included patients developed CDI. Treatment with antibiotics at the time of CDI diagnosis occurred in 7 of 18 (39%) patients. Preoperative history of CDI was significantly associated with increased risk of developing CDI following ileal pouch anal anastomosis (IPAA) compared with those with no prior history of CDI (12 of 18 [67%] vs 11 of 180 [6%]; P < .001). In 16 of 18 (89%) patients, CDI treatment was initiated with predominantly oral vancomycin (72%) or metronidazole (17%)., Conclusion: Although chronic inflammatory conditions of the pouch arise postoperatively, the prevalence of CDI in this population appears to be similar compared with the general population of patients with inflammatory bowel disease prior to and post IPAA. Preoperative CDI appears to be the greatest risk for postoperative CDI and may require extra vigilance in the assessment of CDI after IPAA., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pouchoscopy provides a critical objective measure in the evaluation of patients with suspected inflammatory conditions of the pouch; however, there remain significant gaps in the reliability of the endoscopic scales used in the assessment of these conditions. 1,2 Reliability and reproducibility in the assessment of patients after ileal pouch-anal anastomosis (IPAA) are critical, as evidenced by recent efforts to improve standardization in the evaluation of patients with pouch-related disorders. 3 ., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study., Methods: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors., Results: Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low., Conclusions: In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background & Aims: Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis in the first 2 years after ileal pouch-anal anastomosis and analyze time trends of the incidence of pouchitis., Methods: Using national registries, we established a population-based cohort of all Danish patients undergoing proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after surgery, evaluated by time period. We used Kaplan-Meier and Cox proportional hazard modeling to evaluate the time to development of pouchitis., Results: Overall, 1664 patients underwent an ileal pouch-anal anastomosis. The cumulative incidence of pouchitis in the 2 years after ileal pouch-anal anastomosis increased throughout the study period, from 40% in the period from 1996 to 2000 (95% CI, 35%-46%) to 55% in the period from 2015 to 2018 (95% CI, 48%-63%). Patients undergoing surgery between 2015 and 2018 also showed an increased risk of pouchitis compared with the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (hazard ratio, 1.57; 95% CI, 1.20-2.05)., Conclusions: This population-based study showed a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis shown in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: There is a paucity of validated measures to evaluate how patients feel and function after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. We performed a systematic review to evaluate all published patient reported outcomes (PROs) to assess symptom burden, functional status, and quality of life (QoL) after IPAA., Methods: An electronic literature search on PubMed, Embase, and Web of Science was performed from inception through October 12, 2021. Eligible full texts were further characterized by the type of assessment as well as the individual domains assessed by questions in the PRO measure., Results: Among the 129 full texts analyzed, 51 specific PRO measures were utilized. In the evaluation of all PRO measures, 46% included an assessment of disease-specific QoL with 27% evaluating more general QoL, and 15% assessing symptoms related to pouch function. Among the studies using disease-specific instruments, the Cleveland Clinic Global Quality of Life (42%) and the Inflammatory Bowel Disease Questionnaire (21%) were the most commonly used PRO measures. PRO questions were mapped to individual domains using binning methodology, with the greatest number of questions from individual PRO measures mapped to the bowel function domain (122)., Conclusion: In our assessment of PRO measures among patients after IPAA, the studies and individual measures varied widely in both the patient populations being evaluated as well as outcomes and specific domains being assessed. A valid measure that assesses the range of outcomes after IPAA could standardize assessment and advance the study of patients after IPAA., Competing Interests: Conflicts of Interest: These authors disclose the following: Edward L. Barnes has served as a consultant for AbbVie, Bristol-Meyers Squibb, Lilly, and Target RWE. Hans H. Herfarth has served as a consultant for Alivio, AMAG, BMS, Boehringer, ExeGi Pharma, Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres and research support from Allakos, Artizan, NovoNordisk, Pfizer. Michael D. Kappelman has served as a consultant for Abbvie, Takeda, Janssen, Pfizer, and Eli Lilly and has received research support from Abbvie and Janssen. The remaining authors disclose no conflicts.

Pouchitis, the most common long-term complication after colectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), can lead to increased health care costs and diminished quality of life. 1 In this study, we aimed to compare the total costs among patients diagnosed with pouchitis in the first 2 years after an IPAA with those among patients who were not diagnosed with pouchitis, using a large administrative claims database. Additionally, we aimed to investigate the specific drivers of cost among patients with an IPAA during the 2-year study period, including inpatient hospitalizations, emergency department visits, and pharmacy-related costs., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis has been associated with multiple short- and long-term complications. In this review, we examine the role of biomarkers, imaging, and pouchoscopy in the assessment of patients after ileal pouch-anal anastomosis, with a particular focus on the emergence of novel biomarkers and techniques for evaluating and risk stratifying patients after this procedure in the hopes of improving outcomes in this specific population., Recent Findings: There are indications that that the incidence of pouchitis may be increasing in recent decades. Calprotectin and other non-invasive imaging tests such as ultrasound may offer advantages in distinguishing patients with inflammatory conditions of the pouch from other etiologies. In the search for other biomarkers that may identify patients at risk for inflammatory conditions of the pouch, the stool microbiota and metabolomics may play a key role in identifying those patients at greatest risk for complications. Advances in biomarkers, imaging, and standardized pouchoscopy scoring offer immediate improvements in clinical care and will prompt future research efforts., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis., Aims: We aimed to investigate whether a shorter period between pouch creation and restoration of fecal flow through an IPAA was associated with an increased risk of development of pouchitis within the first 2 years after IPAA., Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. We used Kaplan-Meier testing and Cox Proportional Hazards Modeling to evaluate the relationship between the time between restoration of fecal continuity and time to subsequent development of pouchitis, adjusting for other clinical and demographic factors., Results: We identified 624 patients who underwent proctocolectomy with IPAA for UC, of whom 246 (39%) developed pouchitis within the first 2 years after IPAA. There was no difference when comparing the median time to restoration of continuity among those patients who developed pouchitis and those who did not (49 days vs. 49 days, p = 0.85) or in multivariable analysis. Primary sclerosing cholangitis (Hazard Ratio [HR] 2.14, 95% CI 1.12-4.08), family history of inflammatory bowel disease (HR 1.49, 95% CI 1.08-2.06), and delayed pouch creation (HR 0.75, 95% CI 0.57-1.00) were significantly associated with time to development of pouchitis., Conclusion: Although a staged approach to IPAA may have benefits in the surgical management of UC, the timing interval between pouch creation and restoration of continuity did not impact the subsequent development of early pouchitis in this cohort., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Goals: The goal of this study was to compare the relative safety of administering iron infusions on the same day as intravenous (IV) biological therapy to the administration of these treatments on different days in patients with inflammatory bowel disease (IBD)., Background: IV iron therapy is often required in patients with IBD. Many patients with IBD who receive IV iron therapy in the outpatient setting also receive biological infusion therapy for treatment of their IBD., Study: Patients with IBD who received IV iron therapy at a single infusion center were included. We compared documented infusion-related reactions in patients with patients receiving an iron infusion on the same day as their biological infusion to those who received their iron infusion on a different day., Results: Among 481 patients, 129 received an iron infusion on the same day as a biologic infusion. There was no significant difference in the incidence of infusion reaction when comparing patients who received biological infusion therapy in the same session as the iron infusion to those patients who received a biological infusion on a different day (5% vs. 7%, P =0.246) or any IBD-related therapy (5% vs. 8%, P =0.206)., Conclusions: The frequency and type of infusion reactions in patients receiving IV iron therapy on the same day after IV therapy with biologics was not increased compared with patients who received a biological infusion on a different day. A sequential infusion of biological therapy followed by IV iron therapy may be a safe and cost-effective approach., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite highly effective therapies, many children develop medically refractory ulcerative colitis (UC) and undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We sought to determine the incidence, risk, and burden of pouchitis in the first 2 years following the final stage of IPAA in pediatric UC patients., Methods: Within the IQVIA Legacy PharMetrics Adjudicated Claims Database, we identified pediatric patients with UC who underwent proctocolectomy with IPAA between January 1, 2007, and June 30, 2015. We utilized International Classification of Diseases-Ninth Revision-Clinical Modification or International Classification of Diseases-Tenth Revision-Clinical Modification codes to identify patients with UC and Current Procedural Terminology codes to identify colectomy and IPAA. Continuous variables were compared using t tests and Wilcoxon rank sum testing, while categorical variables were compared using chi-square testing., Results: A total of 68 patients with an IPAA were identified. In the first 2 years following IPAA, the cumulative incidence of pouchitis was 54%. Patients with pouchitis required more outpatient visits in the first 2 years after IPAA (mean 21.8 vs 10.2; P = .006) and were more likely to be hospitalized compared with patients without pouchitis (46% vs 23%; P = .045). Patients with pouchitis also demonstrated higher mean total costs in year 1 and year 2 ($27 489 vs $8032 [P = .001] and $27 699 vs $6058 [P = .003], respectively)., Conclusions: Our findings confirm the high incidence of pouchitis demonstrated in earlier single-center studies of pediatric patients undergoing proctocolectomy with IPAA for UC. Identification of risk factors for pouchitis would be useful to optimize early intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders., Methods: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures., Results: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy ( P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment., Conclusions: In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery., Methods: We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration., Results: A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI., Conclusions: Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non-inflammatory bowel disease control patients., Methods: Colonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non-inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types., Results: Our analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type-specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type-specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes., Conclusions: Single-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Individuals with inflammatory bowel disease (IBD) are up to twice as likely to suffer from anxiety and/or depression. Collaborative care management (CoCM) is an evidence-based approach to treating behavioral health disorders that have proven effective for a range of conditions in primary care and some specialty settings. This model involves a team-based approach, with care delivered by a care manager (case reviews and behavioral therapy), psychiatrist (case reviews and psychopharmacological recommendations), and medical provider (ongoing care including psychopharmacological prescriptions). We assessed the feasibility and effectiveness of CoCM in reducing anxiety and depressive symptoms in patients with IBD., Methods: Patients with psychological distress identified by clinical impression and/or the results of the Patient Health Questionaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were referred to the CoCM program. Data from our 9-month CoCM pilot were collected to assess depression and anxiety response and remission rates. We obtained provider surveys to assess provider acceptability with delivering care in this model., Results: Though the SARS-CoV2 COVID-19 pandemic interrupted screening, 39 patients enrolled and 19 active participants completed the program. Overall, 47.4% had either a response or remission in depression, while 36.8% had response or remission in anxiety. The gastroenterologists highly agreed that the program was a beneficial resource for their patients and felt comfortable implementing the recommendations., Discussion: CoCM is a potentially feasible and well accepted care delivery model for treatment of depression and anxiety in patients with IBD in a specialty gastroenterology clinic setting., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA., Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis., Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08)., Discussion/conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC., Competing Interests: Edward L. Barnes has served as a consultant for AbbVie, Gilead, Pfizer, Takeda, and Target RWE. Bharati Kochar has served as a consultant for Pfizer. Michael D. Kappelman has served as a consultant for Abbvie, Takeda, Janssen, and Eli Lilly and has received research support from Abbvie and Janssen. Millie D. Long has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, and Target Pharmasolutions and has received research support from Pfizer and Takeda. Hans H. Herfarth has served as a consultant for Alivio, AMAG, Finch, Gilead, Lycera, Merck, Otsuka, Pfizer, PureTech, and Seres and research support from Pfizer and Artizan Biosciences. Joshua Hudson, Scott Esckilsen, Mark Koruda, and Robert S. Sandler have no relevant disclosures or conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Background: The optimal restorative surgical management of patients with concomitant diagnoses of primary sclerosing cholangitis and ulcerative colitis [PSC-UC] who require colectomy is controversial, given that patients may have an increased risk for pouchitis after ileal pouch-anal anastomosis [IPAA]. We aimed to compare rates of pouchitis and pouch failure among patients with and without PSC by performing a systematic review and meta-analysis., Methods: A systematic search performed through August 18, 2020, identified 12 studies that compared the rates of pouchitis [n = 11] and/or pouch failure [n = 6] among patients with PSC-UC and UC alone. We then performed a meta-analysis using random effects modelling to estimate the odds of developing any episodes of pouchitis or pouch failure., Results: A total of 4108 patients underwent an ileal pouch-anal anastomosis after proctocolectomy for UC. Of these, 3799 [92%] were performed for UC alone and 309 [8%] were performed for PSC-UC. In a meta-analysis of 11 studies, patients with PSC-UC compared with UC alone were significantly more likely to develop any pouchitis (63% vs 30%, odds ratio [OR] 4.21, 95% confidence interval [CI] 2.86-6.18), chronic pouchitis [47% vs 15%, OR 6.37, 95% CI 3.41-11.9], and pouch failure [10% vs 7%, OR 1.85, 95% CI 1.08-3.17]., Conclusions: Patients with PSC-UC were more likely to experience pouchitis and pouch failure than patients with UC alone. The risks of inflammatory complications after IPAA must be weighed against the potential complications with other surgical procedures, and future studies comparing outcomes among these procedures may inform decision making in this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA., Methods: We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital., Results: Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%-52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%-33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%-22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P < .001). Patients who developed pouchitis were more likely to have a history of primary sclerosing cholangitis (adjusted odds ratio [aOR], 3.94; 95% CI, 1.05-14.8) and anti-tumor necrosis factor alpha therapy prior to colectomy (aOR 1.63; 95% CI, 1.09-2.45). Among patients with pouchitis, the cumulative frequency of new immunosuppressive therapy was 40% (95% CI, 35%-46%) and the cumulative incidence of pouch excision was 1.0% (95% CI, 0.4%-3.0%). The cumulative incidence of a new diagnosis of Crohn's disease after IPAA for UC was 9.0% (95% CI, 7.2%-11%)., Conclusions: In a geographically diverse population, 48% of patients with UC developed pouchitis within the first 2 years after IPAA. Patients with pouchitis had greater use of healthcare resources, indicating a significant burden of disease., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10-4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery. 1 Although up to 80% of patients can develop pouchitis symptoms, 2 , 3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease 4-6 ; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: It is difficult to predict relapse in quiescent ulcerative colitis (UC), but newer endoscopic and histological indices could improve this. This study aimed to determine in UC patients in clinical remission (1) the prevalence of active endoscopic and histological disease; (2) the correlation between endoscopic and histological scores; and (3) the predictive power of these scores for clinical relapse., Design: This multicenter prospective cohort study conducted by the Crohn's and Colitis Foundation Clinical Research Alliance included 100 adults with UC in clinical remission undergoing surveillance colonoscopy for dysplasia. Endoscopic activity was assessed using the Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and ulcerative colitis colonoscopic index of severity (UCCIS). Histology was assessed with the Riley index subcomponents, total Riley score, and basal plasmacytosis., Results: Only 5% of patients had an MES of 0, whereas 38% had a score of 2 to 3; using the UCEIS, the majority of patients had at least mild activity, and 15% had more severe activity. Many patients also had evidence of histological disease activity. The correlations among endoscopic indices, histological subcomponents, and total score were low; the highest correlations occurred with the subcomponent architectural irregularity (ρ = 0.43-0.44), total Riley score (ρ = 0.35-0.37), and basal plasmacytosis (ρ = 0.35-0.36). Nineteen patients relapsed clinically over 1 year, with the subcomponent architectural irregularity being the most predictive factor (P = 0.0076)., Conclusions: This multicenter prospective study found a high prevalence of both endoscopic and histological disease activity in clinically quiescent UC. The correlations between endoscopy and histology were low, and the power to predict clinical relapse was moderate., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)