Objectives: Infliximab (IFX) is commonly used to treat children with inflammatory bowel disease (IBD). We previously reported that patients with extensive disease started on IFX at a dose of 10 mg/kg had greater treatment durability at year one. The aim of this follow-up study is to assess the long-term safety and durability of this dosing strategy in pediatric IBD. Methods: We performed a retrospective single-center study of pediatric IBD patients started on IFX over a 10-year period. Results: Two hundred ninety-one patients were included (mean age = 12.61, 38% female) with a follow-up range of 0.1–9.7 years from IFX induction. One hundred fifty-five (53%) were started at a dose of 10 mg/kg. Only 35 patients (12%) discontinued IFX. The median duration of treatment was 2.9 years. Patients with ulcerative colitis (P ≤ 0.01) and patients with extensive disease (P = 0.01) had lower durability, despite a higher starting dose of IFX (P = 0.03). Adverse events (AEs) were observed to occur at a rate of 234 per 1000 patient-years. Patients with a higher serum IFX trough level (≥20 µg/mL) had a higher rate of AEs (P = 0.01). Use of combination therapy had no impact on risk of AEs (P = 0.78). Conclusions: We observed an excellent IFX treatment durability, with only 12% of patients discontinuing therapy over the observed timeframe. The overall rate of AEs was low, the majority being infusion reactions and dermatologic conditions. Higher IFX dose and serum trough level> 20 µg/mL were associated with higher risk of AEs, the majority being mild and not resulting in cessation of therapy.

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.

BACKGROUND: Online portals have been shown to be a valuable tool for patients to improve compliance with medical treatment in numerous studies across medical specialties. Our aim was to study the effects of the use of web-based applications that allow patients to track their appointments, labs, and provider visit notes on achievement of renal transplantation. STUDY DESIGN: This is a retrospective chart review of patients in 2 outpatient dialysis centers associated with a 719-bed tertiary care academic medical center. RESULTS: Nine percent of portal users at 3 years after initiation of hemodialysis were the recipients of kidney transplants vs 9% of nonusers. At 4 years, 23% of users were transplant recipients vs 13% of nonusers. At 5 years, 40% of users were transplant recipients vs 14% of nonusers. There was statistically significant divergence of the curves, with the greatest difference observed at 5 years (p = 0.047). In addition, increased number of logins per month was associated with shortened time to renal transplantation (p = 0.0067). CONCLUSIONS: Online portal use is associated with a higher likelihood of being approved as a transplantation candidate and increased number of logins is associated with shortened time to renal transplantation. (C) 2020 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Background The literature provides conflicting data on sexual function in women with inflammatory bowel disease (IBD). We aim to describe sexual function at baseline and over time in a prospective inception cohort of adult women with IBD. Methods Women age 18 years or older enrolled in the Ocean State Crohn's & Colitis Area Registry (OSCCAR) with 2 years of prospective follow-up were included in the study. All subjects were enrolled within 1 year of IBD diagnosis. Female sexual function was assessed using the Female Sexual Function Index (FSFI). Linear mixed effects models were used to assess changes in FSFI by various demographic and clinical factors. Results One hundred sixteen of 130 eligible women (89%) were included in the study. Ninety-seven percent of women had sexual dysfunction, defined as an FSFI score of <26.55, with a baseline mean FSFI score (SD) of 16.4 (8.4) overall (15.5 [8.6] in Crohn's disease, 17.4 [8.1] in UC, P = 0.22). Despite improvement in overall disease activity, there was no significant change in the FSFI score or individual domain scores over the entire 2-year study period. Among all women with IBD, older age, nonsingle marital status, lower Short Form Health Survey (SF-36) Physical Component Summary score, and the use of biologics were independent risk factors for sexual dysfunction. Conclusions Almost all women experienced sexual dysfunction that did not improve over time despite improvement in overall disease activity. Future studies are warranted to identify underlying mechanisms that explain the associations between demographic and clinical factors and sexual dysfunction among newly diagnosed women.

An amendment to this paper has been published and can be accessed via the original article.

BACKGROUND: B-cell lymphoma (BCL)2 family members induce or abolish apoptosis.Activation and differentiation of fibroblasts is linked to the expression of the BCL2 family.As fibroblasts are activated during fibrosis, decreasing BCL2 might represent a potential treatment approach.Fibrosis as a common problem in patients with Crohn's disease (CD) is resulting from an imbalance towards excessive fibrous tissue formation driven by fibroblasts.We investigated the impact of BCL2 repression on fibrogenesis.METHODS: Fibroblasts were stimulated with the BCL2 antagonist ABT-737 (AbbVie, USA, final concentration 0.01 -100 nM).BCL2, BCLXL, a-SMA and COL1A1 were determined by qPCR, IF and WB.The impact of BCL2 antagonist treatment on TGF b signaling pathways in primary human colonic fibroblasts was investigated using WB and IF. mRNA expression pattern in primary human colonic fibroblasts was determined by Next Generation Sequencing (NGS).For in vivo experiments, both the murine heterotopic transplantation model of intestinal fibrosis and the model of dextran sodium sulfate (DSS)-induced chronic colitis were used.Animals received BCL2 antagonist (50 mg/kg/day, intraperitoneally (i.p.)).Collagen layer thickness and hydroxyproline (HYP) content were determined.RESULTS: BCL2 and BCLXL were significantly decreased in primary human colonic fibroblasts upon administration of 1nM and 10nM BCL2 antagonist treatment compared to vehicle in a dose-dependent manner (0.68 ± 0.12 and 0.49 ± 0.04 vs. 1.00 ± 0.00, respectively, * p < 0.05 for BCL2, 0.41±0.26and 0.35±0.22 vs. 1.00 ± 0.00, respectively, * p < 0.05 for BCLXL).COL1A1 and a-SMA were decreased in both human and murine colonic fibroblasts upon BCL2 antagonist treatment compared to vehicle.WB analysis revealed a decrease of pERK1, pERK2 and SMAD3 from the TGFb signaling pathways in primary human fibroblasts in a dose dependent manner upon BCL2 antagonist treatment compared to vehicle.NGS and qPCR revealed a link to the transcription factors GATA6 and SOX9 for mediating pro-fibrotic effects and for reprogramming fibroblasts.Collagen layer thickness was significantly decreased in the mouse model of fibrosis upon BCL2 antagonist administration compared to vehicle (* p < 0.05).Decreased HYP content upon BCL2 antagonist administration confirmed the preventive effects of the BCL2 antagonist on intestinal fibrosis in vivo.CONCLUSION: The BCL2 antagonist changed the expression profile of BCL2 family members and prevented fibroblast differentiation into myofibroblasts.BCL2 antagonist administration partially prevented intestinal fibrogenesis in both the murine heterotopic transplantation model of intestinal fibrosis and the DSS-induced chronic colitis model and therefore may represent a potential treatment option against CD associated fibrosis.

that maternal IBD affects both the offspring’s immediate and long-term morbidity, specifically congenital anomalies and neurodevelopmental problems have been described. In current study, we examined the impact of maternal IBD on the longterm risk of disease in the offspring during childhood and adolescence compared to children born by women without IBD. Methods: This nationwide cohort study was based on the Danish health registries including all children born alive in Denmark between 1989 and 2013. We assessed the association between maternal IBD and diagnosed diseases in the offspring according to 10 selected categories of physical and mental diseases (diabetes, thyroid disease, rheumatoid arthritis, IBD, epilepsy, chronic lung disease/asthma, mood affective disorders, schizophrenia/other paranoid psychoses, nervous conditions and congenital malformations). The time span from birth until diagnosis, or end of follow-up, was described and we computed the hazard ratios for child disease using Cox proportional hazard regression and logistic regression for the relative risk of congenital malformations diagnosed within the first year of life. The statistical models were adjusted for the following covariates; gender, year of birth, maternal age, mode of delivery, multiple birth, birth order, preterm birth, BMI and comorbidity. Stratification on IBD subtype; Crohn s disease and ulcerative colitis, was carried out in a sub analysis. Results: The exposed cohort comprised 9238 children born by women with IBD, and the unexposed cohort of 1,371,407 children born by women without IBD followed from date of birth. The unexposed cohort was followed for a median time of 13.8 years and the exposed cohort for a median time of 9.7 years. In both groups the maximum time of follow-up was 25.9 years. We found that children born by mothers with IBD had an almost 6 times increased risk of being diagnosed with IBD compared with children born by mothers without IBD adjusted HR (95% CI): 5.67 (4.63–6.96). Apart from this partially expected finding, children born by mothers with IBD were not more likely to be diagnosed with any of the other included diagnoses. The risk estimates for all other childhood disease categories were close to unity, and we did not find significantly increased risk for any of the other diseases. When stratifying for IBD subtypes the risk of IBD was even more pronounced in the Crohn s disease group; adjusted HR (95% CI): 7.59 (5.65–10.19), than in the ulcerative colitis group. Conclusions: From this huge study on long-term health consequences in children born by mothers with IBD the association showed an expected increased risk of IBD in the offspring. We did not find evidence for an increased risk of any of the other examined diseases in the offspring. This finding is very reassuring for women with IBD regarding the long-term reproductive outcomes in their offspring.

Patients with inflammatory bowel disease (IBD) may be exposed to high doses of diagnostic radiation. The purpose of this study is to identify subsets of this population at risk for significant radiation exposure.

Background:Studies describing the incidence of Crohn's disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island.Methods:The Ocean State Crohn's and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010.Results:A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3-32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohn's and Colitis Area Registry for follow-up.Conclusions:The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohn's and Colitis Area Registry cohort is ongoing.

Studies describing the incidence of Crohn's disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island. The Ocean State Crohn's and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010. A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3–32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohn's and Colitis Area Registry for follow-up. The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohn's and Colitis Area Registry cohort is ongoing.

Introduction: The prognostic value of seromarkers in inflammatory bowel disease (IBD) has been studied in tertiary referral center populations. We investigated the relationship between seromarker positivity and disease course in newly-diagnosed Crohn's disease (CD) in a community-based cohort. Methods: The Ocean State Crohn's and Colitis Area Registry is a prospective, community-based cohort of patients with newly-diagnosed IBD enrolled from 2008 to 2013. Clinical diagnosis was confirmed by NIDDK IBD Genetics Consortium criteria. Serum was banked at enrollment for subsequent testing. Patients were followed prospectively for a median (interquartile range) of 60.1 (35.7) months for hospitalizations, surgeries, and therapy initiation. Seropositive CD was defined as a clinical diagnosis of CD with two or more positive seromarkers. Seronegative CD was defined as a clinical diagnosis of CD with one or less positive seromarkers. CRP positivity and disease behavior per Montreal Classifications were compared between seropositive and seronegative patients. Time to first hospitalization, surgery, steroid, immunomodulator, or biologic was compared between seropositive and seronegative patients using the Wilcoxon test. Results: Of the 225 newly-diagnosed CD patients, 126 were seropositive and 99 were seronegative. Seronegative patients had lower rates of elevated CRPs than seropositive patients (28.3% vs 61.1%, p < 0.0001). Seronegative patients demonstrated lower rates of stricturing and penetrating disease and higher rates of inflammatory disease behavior when compared with seropositive patients (8.1%, 7.1%, 84.9% vs. 19.8%, 15.1%, 65.1%, p = 0.004). Seronegative patients possessed lower rates of perianal disease compared with seropositive patients (4.0% vs. 11.1%, p = 0.05) (Table 1). At 6, 12, and 24 month follow-up, fewer seronegative patients than seropositive patients experienced disease progression in the form of steroid, immunomodulator, or biologic initiation, hospitalization, or intra-abdominal surgery (Table 2). There was no difference between seronegative and seropositive patients in time to first disease progression event (p= 0.11).Table 1: Baseline Disease Phenotype at Diagnosis in Seronegative and Seropositive Newly Diagnosed Community Crohn's Disease PatientsTable 2: Progression of Disease at 6, 12 and 24 Months in Seronegative and Seropositive Newly-diagnosed Community Crohn's Disease PatientsConclusion: Seropositive CD is associated with higher rates of elevated CRP and more severe disease phenotype. Although we did not detect differences in time to hospitalization, surgery or treatment with advanced therapies, duration of follow-up was limited. Seronegative CD in community-based patients may have a favorable prognosis.

Background: Traditional cohort studies are important contributors to our understanding of inflammatory bowel diseases, but they are labor intensive and often do not focus on patient-reported outcomes. Internet-based studies provide new opportunities to study patient-reported outcomes and can be efficiently implemented and scaled. If a traditional cohort study was linked to an Internet-based study, both studies could benefit from added synergy. Existing cohort studies provide an opportunity to develop and test processes for cohort linkage. The Crohn's and Colitis Foundation of America's (CCFA) Partners study is an Internet-based cohort of more than 14,000 participants. The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is an inception cohort. The Sinai-Helmsley Alliance for Research Excellence (SHARE) is a multicentered cohort of inflammatory bowel disease patients. Both the later cohorts include medical record abstraction, patient surveys, and biospecimen collection.Objective: Given the complementary nature of these existing cohorts, we sought to corecruit and link data.Methods: Eligible OSCCAR and SHARE participants were invited to join the CCFA Partners study and provide consent for data sharing between the 2 cohorts. After informed consent, participants were directed to the CCFA Partners website to complete enrollment and a baseline Web-based survey. Participants were linked across the 2 cohorts by the matching of an email address. We compared demographic and clinical characteristics between OSCCAR and SHARE participants who did and did not enroll in CCFA Partners and the data linkage.Results: Of 408 participants in the OSCCAR cohort, 320 were eligible for participation in the CCFA Partners cohort. Of these participants, 243 consented to participation; however, only 44 enrolled in CCFA Partners and completed the linkage. OSCCAR participants who enrolled in CCFA Partners were better educated (17% with doctoral degrees) than those who did not (3% with doctoral degrees, P=.01). In the SHARE cohort, 436 participants enrolled and linked to the Partners cohort. More women (60% vs 50%) linked and those who linked were predominantly white (96%; P<.01). Crohn's disease patients who linked had lower mean scores on the Harvey-Bradshaw Index (3.6 vs 4.4, P<.01). Ulcerative colitis patients who linked had less extensive disease than those who did not link (45% vs 60%, P<.01).Conclusions: Linkage of CCFA Partners with cohorts such as OSCCAR and SHARE may be a cost-effective way to expand the infrastructure for clinical outcomes and translational research. Although linkage is feasible from a technical, legal, and regulatory perspective, participant willingness appears to be a limiting factor. Overcoming this barrier will be needed to generate meaningful sample sizes to conduct studies of biomarkers, natural history, and clinical effectiveness using linked data.

Background:Crohn's disease (CD) is a form of inflammatory bowel disease with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of inflammatory bowel disease. We performed a pilot study to examine differences in the proteome among patients with stricturing CD, nonstricturing CD, and ulcerative colitis.Methods:Serum samples were selected from the Ocean State Crohn's and Colitis Area Registry, an established cohort of patients with inflammatory bowel disease. Patients with CD with surgically resected stricture were matched with similar patients with CD without known stricture and with ulcerative colitis. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture.Results:Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the 3 groups. We quantified 7668 peptides and 897 proteins for analysis. Receiver operating characteristic analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides and determined their function based on previously published literature.Conclusions:The serum of patients with stricturing CD, nonstricturing CD, and ulcerative colitis is distinguishable through proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.