Search

Background & Aims: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort., Methods: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses., Results: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002)., Conclusions: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this., (Published by Elsevier Inc.)

Introduction: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing., Methods: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD., Results: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even ≥5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition., Discussion: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals., (Copyright © 2023 by The American College of Gastroenterology.)

Effective immunity requires a large, diverse naive T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we addressed how S1P enables T cell survival and the implications for patients treated with S1PR1 antagonists. We found that S1PR1 limited apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization were required to prevent this proapoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naive T cells limited B cell responses. Our findings highlighted an effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggested both limitations and additional uses of this important class of drugs.

Background: Inflammatory bowel disease [IBD] has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear., Methods: We identified 41 880 individuals with IBD (Crohn's disease [CD: n = 12 850]; ulcerative colitis [UC]: n = 29 030]) from Sweden matched with 41 880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios [aHRs] for neoplastic colorectal polyps [tubular, serrated/sessile, advanced and villous] defined by histopathology codes., Results: During follow-up, 1648 [3.9%] IBD patients and 1143 [2.7%] reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10 000 person-years, respectively. This correlated to an aHR of 1.23 (95% confidence interval [CI] 1.12-1.35) with the highest HRs seen for sessile serrated polyps [8.50, 95% CI 1.10-65.90] and traditional serrated adenomas [1.72, 95% CI 1.02-2.91]. aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and at 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD [aHRs 1.31 vs 1.06, respectively], with a 20-year cumulative risk difference of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis., Conclusions: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease., (© The Author(s) 2023. 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: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer., Methods: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores., Results: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77)., Conclusions: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist., (Copyright © 2023. Published by Elsevier Inc.)

Background: Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR)., Methods: We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab)., Results: We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis., Conclusion: Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited., (© 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.)

Introduction: Enteric infection with Clostridioides difficile , Escherichia coli subtypes, and norovirus is commonly detected in flares of inflammatory bowel disease (IBD). We associated the gut microbiome during flare complicated by a gastrointestinal pathogen with outcomes of IBD., Methods: We performed a cross-sectional study of 260 patients (92 IBD and 168 non-IBD) with a gastrointestinal polymerase chain reaction panel positive for C. difficile, E. coli , or norovirus, or negative during an episode of diarrhea from 2018 to 2020, and 25 healthy controls. Clinical variables, IBD status, and 2-year outcomes were collected. Using 16S rRNA sequencing, we measured the effect size of the gut microbiome on IBD characteristics and outcomes., Results: There were major differences in the gut microbiome between patients with and without a pathogen and IBD. In IBD, a higher proportion of patients without a pathogen required hospitalization and IBD therapies at flare and within the 2 years after flare, driven by a milder disease course in flares complicated by an E. coli subtype or norovirus. Examining the contribution of clinical covariates, the presence of IBD, and C-reactive protein, C. difficile had a greater relative influence on the gut microbiome compared with the presence of an E. coli subtype or norovirus. In patients with C. difficile or no pathogen, lower microbiome diversity at flare was associated with adverse IBD outcomes over 2 years., Discussion: Distinctive pathogen-specific gut microbiomes were associated with subsequent IBD outcomes. These findings may have direct implications for the management of IBD flares complicated by enteric pathogens., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: There is little data regarding the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a prior history of cancer who are exposed to ustekinumab or vedolizumab. We assessed the risk of subsequent cancer in patients exposed to these agents., Methods: We performed a retrospective cohort study of patients with IBD and a history of cancer at an academic medical center between January 2013 and December 2020. We collected data on demographics, IBD and cancer disease characteristics, and drug exposures. The primary exposure was immunosuppressive therapy after diagnosis of cancer. The primary outcome was interval development of new or recurrent cancer., Results: Of 390 patients with IBD and a previous history of cancer, 37 were exposed to vedolizumab, 14 ustekinumab, 41 antitumor necrosis factor (anti-TNF), and 31 immunomodulator; and 267 were not exposed to immunosuppression following cancer diagnosis. During a total median follow-up time of 52 months, 81 (20%) patients developed subsequent cancer: 6 (16%) were exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to immunomodulators, 12 (29%) to anti-TNF, and 56 (21%) with no immunosuppression (P = .41). In a multivariable Cox model adjusting for age, IBD subtype, smoking, cancer recurrence risk, and cancer stage, there was no increase in subsequent cancer with vedolizumab (adjusted hazard ratio, 1.36; 95% CI, 0.27-7.01) or ustekinumab (adjusted hazard ratio, 0.96; 95% CI, 0.17-5.41). Patients with more than 1 biologic exposure also did not have an increased risk of subsequent cancer., Conclusions: Exposure to ustekinumab or vedolizumab in patients with IBD and a prior history of cancer does not appear to be associated with an increased risk of subsequent new or recurrent cancer., (© 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.)

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19., (© 2022. The Author(s).)

Ulcerative colitis is one of the two main subtypes of inflammatory bowel disease, along with Crohn's disease. Understanding the clinical and endoscopic features of ulcerative colitis is critical in achieving a timely diagnosis. An initial evaluation includes assessing clinical symptoms, inflammatory markers, endoscopic findings, and determination of the presence or absence of extraintestinal manifestations. Initial disease management should consider disease severity at the time of diagnosis as well as prognostication, or the determination of risk factors present with a high likelihood of severe disease in the future. Once appropriate therapy has been initiated, ongoing monitoring is crucial, which may include repeated clinical assessments over time, measuring noninvasive markers of inflammation, and endoscopic and histologic reevaluation. An important aspect of disease monitoring in ulcerative colitis is dysplasia surveillance; there are many patient-specific risk factors which influence surveillance strategies. Utilizing appropriate surveillance techniques is necessary for early detection of dysplasia and colorectal neoplasia., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Loss of Paneth cells and their antimicrobial granules compromises the intestinal epithelial barrier and is associated with Crohn's disease, a major type of inflammatory bowel disease 1-7 . Non-classical lymphoid cells, broadly referred to as intraepithelial lymphocytes (IELs), intercalate the intestinal epithelium 8,9 . This anatomical position has implicated them as first-line defenders in resistance to infections, but their role in inflammatory disease pathogenesis requires clarification. The identification of mediators that coordinate crosstalk between specific IEL and epithelial subsets could provide insight into intestinal barrier mechanisms in health and disease. Here we show that the subset of IELs that express γ and δ T cell receptor subunits (γδ IELs) promotes the viability of Paneth cells deficient in the Crohn's disease susceptibility gene ATG16L1. Using an ex vivo lymphocyte-epithelium co-culture system, we identified apoptosis inhibitor 5 (API5) as a Paneth cell-protective factor secreted by γδ IELs. In the Atg16l1-mutant mouse model, viral infection induced a loss of Paneth cells and enhanced susceptibility to intestinal injury by inhibiting the secretion of API5 from γδ IELs. Therapeutic administration of recombinant API5 protected Paneth cells in vivo in mice and ex vivo in human organoids with the ATG16L1 risk allele. Thus, we identify API5 as a protective γδ IEL effector that masks genetic susceptibility to Paneth cell death., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer., Competing Interests: Disclosure J.E. Axelrad reports receiving research grants from BioFire Diagnostics; consultancy fees or honorarium from BioFire Diagnostics, Janssen, Pfizer, Abbvie, and BMS; and holds US Patent 2012/0052124A1 and no other conflicts of interest. A.K. Holmer reports consultancy fees or honorarium from Pfizer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Colorectal strictures have been considered independent risk factors for neoplasia in patients with inflammatory bowel disease (IBD). We examined the association between colorectal stricture and subsequent risk of colorectal neoplasia (CRN) in patients with IBD colitis undergoing colonoscopic surveillance., Methods: We conducted a retrospective cohort analysis of patients with IBD colitis enrolled in colonoscopic surveillance for CRN at an academic medical center between 2005 and 2017. Inclusion criteria were IBD involving the colon for ≥8 years (or any duration with primary sclerosing cholangitis [PSC]) undergoing surveillance. Exclusion criteria were advanced CRN (ACRN; colorectal cancer [CRC] or high-grade dysplasia [HGD]) prior to or at enrollment, prior colectomy, or limited (<30%) disease extent or proctitis. Multivariable logistic and Cox regression analysis estimated the association between colorectal stricture on the index colonoscopy and ACRN, CRN (indefinite dysplasia, low-grade dysplasia, HGD, CRC), or colectomy., Results: Among 789 patients with IBD undergoing CRC surveillance, 72 (9%; 70 with Crohn's colitis) had a colorectal stricture on index colonoscopy. There was no significant difference in the frequency of ACRN or requirement for colectomy between patients with vs without a colorectal stricture (P > .05). Colorectal stricture was not associated with subsequent ACRN (adjusted odds ratio [aOR], 1.41; 95% CI, 0.49-4.07), CRN (aOR, 1.15; 95% CI, 0.51-2.58), or colectomy (aOR, 1.10; 95% CI, 0.65-1.84)., Conclusions: In this analysis of patients with IBD colitis undergoing CRN surveillance, the presence of a colorectal stricture was not independently associated with risk of ACRN or colectomy. Multicenter, prospective studies are needed to confirm these findings, particularly in patients with ulcerative colitis-associated colorectal stricture., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: JUS reports consultancy fees from Janssen, Novartis, Pfizer, Sanofi, UCB, AbbVie, and Amgen, and funding for investigator-initiated studies from Pfizer, Sanofi, and Janssen. MJM reports laboratory research and clinical trials contracts with Lilly, Pfizer, and Sanofi, and personal fees for scientific advisory board service from Merck, Meissa Vaccines, and Pfizer. PMI reports consulting fees from GlaxoSmithKline and Momenta/Janssen. RHH reports consulting fees from Janssen. SA reports grant support from Johnson & Johnson. GS reports consulting fees from AbbVie. DPH reports consultancy fees from AbbVie, Bristol Myers Squibb, Janssen, Takeda, UCB, and Pfizer, and reports research support from Janssen and Pfizer. JEA reports consultancy fees from BioFire Diagnostics and Janssen; research grant support from BioFire Diagnostic; and holds US patent 2012/0052124A1. SCh reports consulting fees from AbbVie, Pfizer, and Bristol Myers Squibb. AS reports consulting fees from Lilly, GlaxoSmithKline, AstraZeneca, and Kezar. ALN reports consultancy fees from Janssen, UCB, AbbVie, and Bristol Myers Squibb, and her immediate family member owns shares of stock in Johnson & Johnson, Eli Lilly, AbbVie, and Pfizer. All other authors declare no competing interests. RHH, SU, and JEA contributed equally to this paper. DPH and JUS contributed equally to this paper. All data relevant to the study are included in the article or uploaded as supplementary information. Further de-identified data can be made available upon request via email to the corresponding author. This study was funded by US National Institutes of Health (NIH)–National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR074500 to Scher, T32-AR-069515 to RHH and JUS), NIH–National Institute of Diabetes and Digestive and Kidney Diseases (K23DK124570 to JEA), NIH–National Institute of Allergy and Infectious Diseases (AI082630 and AI158617 to SH), Rheumatology Research Foundation (Scientist Development Award to RHH), Bloomberg Philanthropies, Pfizer COVID-19 Competitive Grant Program, The Beatrice Snyder Foundation, The Riley Family Foundation, Crohn's and Colitis Foundation (to JEA), and the Judith and Stewart Colton Center for Autoimmunity (to JEA). No authors are employed by the NIH. We are grateful to our patients and their families for participating in this study and to our colleagues who referred patients to use. We thank Luz Alvarado, Rhina Medina, Parvathi Girija, and Jyoti Patel for coordinating and for data entry efforts.

Background and Aims: Clostridioides difficile infection (CDI) is associated with a range of outcomes, and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia., Methods: Eosinopenia was defined as 0 eosinophils/ μ L on the soonest peripheral blood drawn within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of 3 large, unaffiliated hospital networks, tested positive for CDI by stool polymerase chain reaction, and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days., Results: There were 4518 unique hospitalized adults with CDI included (2142 in the derivation cohort and 2376 in the validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts. In the validation cohort, the factors most strongly associated with death were eosinopenia (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.77-3.50), albumin <3 g/dL (aOR 3.26, 95% CI 2.13-3.49), and creatinine >1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A 6-variable clinical prediction model was developed that improved on existing classification schemes for CDI severity (area under the receiver operating characteristic curve of 0.75 vs 0.68)., Conclusion: Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification., Competing Interests: Conflicts of Interest: The authors disclose no conflicts.

Background: Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compare the impact of PCR stool testing to conventional stool testing in outpatients presenting with relapse of IBD., Methods: In a retrospective cohort study of outpatients with IBD presenting to NYU Langone Health with flare from September 2015 to April 2019, we compared patients who underwent stool testing with GI PCR to age-, sex-, and IBD-subtype-matched patients who underwent culture and ova and parasite exam (conventional testing). The primary outcome was IBD therapy escalation after testing. Secondary outcomes included rates of posttesting endoscopy, abdominal radiography, antibiotics, and IBD-related emergency department visits, hospitalizations, and abdominal surgeries., Results: We identified 134 patients who underwent GI PCR matched to 134 patients who underwent conventional testing. Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01). We found that GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes. On multivariate analysis, testing with GI PCR was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; P = 0.02) for escalation of IBD therapies., Conclusions: Testing with GI PCR was associated with higher rates of pathogen detection and lower rates of IBD therapy escalation and endoscopy in the outpatient setting. These changes in management were not associated with a difference in IBD outcomes., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis., Methods: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980., Findings: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2-2.5) and tobacco smoke (OR 1.5; 95% CI 1.2-1.9), and early life otitis media (OR 2.1; 95% CI 1.2-3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous., Interpretation: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies., Funding: This study did not receive any funding., Competing Interests: The corresponding author confirms on behalf of all authors that there have been no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. JS reports personal fees from Takeda, Abbvie, and Janssen, and grants from Helmsley Charity Trust Fund and Fonds voor Wetenschappelijk Onderzoek – Vlaanderen, outside the submitted work. TL reports grants from DigestScience foundation and received travel accommodation from Adacyte Therapeutics. JFC reports grants and consultancy and lectures from Abbvie; consultancy and lectures from Ferring Pharmaceutical; consultancy from Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Enterome, Geneva, and Genentech; grants and consultancy from Janssen Pharmaceuticals; consultancy from Landos, LimmaTech Biologics AG, Ipsen, Imedex, Merck, Novartis, O Mass, Ostuka, and Pfizer; consultancy and lectures from Shire; grants, consultancy and lectures from Takeda; consultancy from Tigenix; and is a stock holder with Intestinal Biotech Development and Genfit, outside the submitted work. NN has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring for advisory boards. JT has received research grants from Janssen and Abbvie, speaker fees from Janssen, and Advisory Board fees from Janssen, Pfizer, Arena Pharmaceuticals, Pfizer, Gilead and Galapagos. MA reports grants from Dickler Family Fund, New York Community Trust, grants from Leona M. and Harry B. Helmsley Charitable Trust for SECURE-IBD database, outside the submitted work. All other authors have nothing to disclose., (© 2021 The Authors.)

Background: The Swedish Quality Register for Inflammatory Bowel Disease (SWIBREG) contains clinical data for the study of inflammatory bowel disease (IBD). The Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort was recently established for the study of gastrointestinal histopathology. We aimed to develop and validate a histology score from ESPRESSO using clinical information from SWIBREG, and secondarily, to evaluate the association of the score on IBD-related hospitalization., Methods: In a nationwide, population-based cohort study of patients with IBD during 1969-2017, we linked endoscopic inflammation in SWIBREG with histologic inflammation in ESPRESSO. We established a clinically interpretable model for predicting the endoscopic score from histology using scalable Bayesian rule lists to define a SNOMED-based histology score applicable to the ESPRESSO cohort. We also assessed the impact of baseline endoscopic and histology scores on time to IBD-related hospitalization., Results: We identified 5225 individuals with IBD comprising 11,051 endoscopic assessments in SWIBREG linked to a histopathology record in ESPRESSO. We created predictive models to calculate a SNOMED-based histology score which predicted the endoscopic score. Split-sample validated areas under the ROC curves for the score predicting a non-zero endoscopic score were 0.80 (0.78-0.81) in UC, 0.70 (0.68-0.72) in CD, and 0.76 (0.73-0.78) in IBD-U. In a subset of 2741 individuals with an initial IBD diagnosis and a corresponding record in ESPRESSO with an endoscopic assessment in SWIBREG, the baseline endoscopic and histology scores were associated with time to IBD-related hospitalization (endoscopy log-rank UC p<0.001, CD p=0.020, IBD-U p<0.001; histology log-rank UC p=0.018, CD p=0.960, IBD-U p=0.034)., Conclusion: Histopathology data in ESPRESSO accurately predict endoscopic scores in SWIBREG. Baseline endoscopic and histologic scores were associated with time to IBD-related hospitalization, particularly in UC. The SNOMED-based histology score can be used as a measure of disease activity in future register-based IBD studies., Competing Interests: Dr. Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG) and that study has received funding from Janssen corporation. Dr. Olén has been PI on projects at Karolinska Institutet partly financed by investigator-initiated grants from Janssen and Ferring, and also reports a grant from Pfizer in the context of a national safety monitoring program. None of those studies have any relation to the present study. Karolinska Institutet also has received fees for Olén’s lectures and participation on advisory boards from Janssen, Ferring, Takeda, and Pfizer regarding topics not related to the present study. The authors report no other potential conflicts of interest for this work., (© 2020 Axelrad et al.)

Background: Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization., Methods: We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis., Results: We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P< .01), a 113% increase in therapeutic yield (P= .01), a 27% reduction in the number of procedures per patient (P < .01), a 33% decrease in length of stay (P < .01), and an 18% reduction in estimated costs (P < .01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%)., Conclusions: Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Low socioeconomic status has been linked with numerous poor health outcomes, but data are limited regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by IBD patients based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status., Methods: We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid with all other patients., Results: Of 947 patients with IBD, 221 (23%) had been enrolled in Medicaid. Compared with patients with other insurance types, patients with Medicaid had higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, and ethnicity, patients with Medicaid had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59-3.36) and ED visits (RR 4.24; 95% CI 3.82-4.70) compared to patients with other insurance. Patients with Medicaid had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001), and after adjusting for the same factors, the odds of requiring steroids in the patients with Medicaid was increased (OR 3.77; 95% CI 2.53-5.62)., Conclusions: Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: Enteric tube (ET) placement is approached with caution in patients with esophageal varices (EV) due to concern of causing variceal bleeding. Data are limited on rates and predictors of gastrointestinal bleeding (GIB) in these patients. This study aims to assess the rate and predictors of bleeding from EV after ET placement., Methods: We performed a retrospective chart review on patients requiring ET access with known EV. Inclusion criteria were age >18 with endoscopically proven EV who required ET placement. Patients who were admitted with, or developed a GIB prior to placement of ET were excluded, as were patients admitted for liver transplantation. Primary outcome was incidence of GIB within 48 h of tube placement. Secondary outcome was a >2 g/dL drop in hemoglobin within 48 h of placement without evidence of bleed. Statistical analysis was performed using Fischer's exact test, Mann-Whitney U test, and univariate logistic regression model., Results: A total of 75 patients were included in the analysis. The most common etiology of cirrhosis was alcohol (44%). The most common location of EV was in the lower third of the esophagus (61%). The primary outcome was observed in 11 (14.6%) patients. The secondary outcome was found in eight (10.6%) patients. On univariate analysis, GIB was associated with higher MELD-Na ( P = 0.026) and EV located in the lower third of the esophagus ( P = 0.048)., Conclusion: ET placement in patients with EV is associated with low risk of bleeding. Elevated MELD-Na and lower EV location conferred a higher risk of bleeding after ET placement., (© 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Crohn's disease and ulcerative colitis are chronic inflammatory diseases that lead to progressive bowel damage including the development of stricturing and penetrating complications. Increasingly, cross-sectional imaging with computed tomography or magnetic resonance scans have emerged as leading tools to: (1) assess disease activity; (2) monitor response to therapy or disease recurrence; and (3) identify disease-related complications. Several validated radiological scoring systems have been developed to quantify cross-sectional and longitudinal inflammatory burden in these diseases and to monitor response to treatment. Bowel ultrasound is also a simple and inexpensive tool but is operator dependent in its performance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD), often leading to diagnostic confusion and delays in IBD therapy escalation. This study sought to assess outcomes after CDI in IBD patients exposed to new or escalated immunosuppressive therapy., Methods: This multicenter retrospective cohort study included IBD patients with documented CDI at 4 academic medical centers. Data were abstracted from clinical databases at each institution. Outcomes at 30 and 90 days were compared between patients undergoing new or intensified immunosuppressive therapy and those without therapy escalation. Continuous variables were compared using t tests, and proportions using chi-square tests. Multivariable logistic regression was used to determine the association of individual variables with severe outcomes (including death, sepsis, and/or colectomy) within 90 days. Secondary outcomes included CDI recurrence, rehospitalization, worsening of IBD, and severe outcomes within 30 days., Results: A total of 207 adult patients with IBD and CDI were included, of whom 62 underwent escalation to biologic or corticosteroid therapy (median time to escalation, 13 days). Severe outcomes within 90 days occurred in 21 (15.6%) nonescalated and 1 (1.8%) therapy-escalated patients. Serum albumin <2.5 mg/dL, lactate >2.2 mg/dL, intensive care unit admission, hypotension, and comorbid disease were associated with severe outcomes. Likelihood of severe outcomes was decreased in patients undergoing escalation of IBD therapy after CDI (adjusted odds ratio [aOR], 0.12) and increased among patients aged >65 years (aOR, 4.55)., Conclusions: Therapy escalation for IBD within 90 days of CDI was not associated with worse clinical outcomes. Initiation of immunosuppression for active IBD may therefore be appropriate in carefully selected patients after treatment of CDI., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Few studies have examined the role of non-Clostridium difficile enteric infections in flares of inflammatory bowel disease (IBD). Our objective was to investigate enteric infection detected by multiplex PCR stool testing in patients with IBD., Methods: We performed a cross-sectional analysis of 9403 patients who underwent 13,231 stool tests with a gastrointestinal pathogen PCR panel during a diarrheal illness from March 2015 to May 2017. Our primary outcome was the presence of an infection. Secondary outcomes included endoscopic and histologic predictors of infection, and IBD outcomes following testing., Results: A total of 277 patients with Crohn's disease (CD), 300 patients with ulcerative colitis (UC), and 8826 patients without IBD underwent 454, 503, and 12,275 tests, respectively. Compared to patients without IBD, patients with IBD were less likely to test positive (CD 18.1%, UC 16.1%, no IBD 26.6%, p < 0.001). Compared to patients without IBD, CD had a higher prevalence of norovirus (p = 0.05) and Campylobacter (p = 0.043), whereas UC had a lower prevalence of norovirus (p = 0.001) and a higher prevalence of Campylobacter (p = 0.013), Plesiomonas (p = 0.049), and Escherichia coli species (p < 0.001). Of 77 patients who underwent endoscopy, there were no major endoscopic or histologic predictors of a positive test. Patients who tested negative were more likely to have IBD therapy escalated (p = 0.004). Enteric infection did not impact IBD outcomes following testing (log-rank 0.224)., Conclusions: Non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD. Endoscopic and histologic findings may not differentiate flare from infection. Norovirus and E.coli may play an important role in flare of IBD.

Background: Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients., Methods: We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation., Results: Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%., Conclusions: Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)