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Background The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. Methods A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan–Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. Results In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8–32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25–48%) and 42% [95% CI 32–53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. Conclusions This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup. [ABSTRACT FROM AUTHOR]

Background: There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. Methods: Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. Results: Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. Conclusions: The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. Methodology: Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population‐based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. Results: There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non‐significant increase in risk of ALT flare among the HBV‐exposed group (27.6% vs. 23.7%, p =.055). In multivariable analysis, using prednisolone‐equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti‐CD20 when compared to other biological agents (36.1% vs. 14.5%, p <.01), but was not significantly different among anti‐tumour necrosis factor, anti‐cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti‐integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p =.82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti‐CD20. Conclusions: Our study further supports the current suggestion of prophylactic anti‐viral before starting anti‐CD20 in HBV‐exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation. [ABSTRACT FROM AUTHOR]

Background and Aim: Whether 5‐aminosalicylic acid (ASA) can be stopped in patients with stable ulcerative colitis (UC) remains unclear. We aimed to examine whether 5‐ASA can be safely withdrawn in UC patients who have been in corticosteroid‐free clinical remission for ≥ 1 year. Methods: This is a retrospective cohort study using territory‐wide healthcare database in Hong Kong. Primary outcome was development of UC flare, defined as new corticosteroid use or UC‐related hospitalizations within 5 years. UC patients on oral 5‐ASA ≥ 2 g daily for ≥ 1 year with C‐reactive protein (CRP) < 10 mg/dL and no 5‐ASA dosage escalation, UC‐related hospitalization or corticosteroid use in the past year were included. Patients on biological agents were excluded. Patients were classified as "stopping" if 5‐ASA was withdrawn for ≥ 90 days within follow‐up period. We performed multivariable Cox regression models adjusting for demographics, blood parameters and immunosuppressants used. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was reported comparing stopping and continuous‐use groups. Results: A total of 1408 patients were included with a median follow‐up duration of 41.8 months (interquartile range [IQR]: 17.2–60.0 months). Stopping 5‐ASA was not associated with an increased risk of UC flare (aHR 0.91; 95% CI 0.64–1.31; P = 0.620). A higher CRP levels at the time of stopping 5‐ASA (aHR 1.15; 95% CI: 1.01–1.30; P = 0.037) were associated with increased risk of flare. Conclusion: Stopping 5‐ASA in UC patients in corticosteroid‐free remission for ≥ 1 year was not associated with increased risk of flare. Future prospective trials should evaluate the role of stopping 5‐ASA in stable UC patients. [ABSTRACT FROM AUTHOR]

We conducted a territory wide survey to investigate the epidemiology, risk factors, and clinical outcomes of Clostridioides difficile infection (CDI) among hospitalized patients in Hong Kong. A total of 17,105 cases of CDI were identified, of which 15,717 (91.9%) were healthcare-associated and 1,025 (6.0%) were community-associated. Although CDI incidence increased substantially from 2006 to 2017, it plateaued in 2018 and 2019. The 30-day mortality rates decreased from 20.1% in 2015 to 16.8% in 2019, whereas the 60-day recurrence rates remained constant at ≈11% during the study period. Cross-correlation statistic showed significant correlations between incidence trend and overall antimicrobial drug use (r = 0.865, p<0.001), which has decreased as a result of an antibiotic stewardship program initiated in 2017. Our data suggest a turning point in C. difficile epidemiology that could be related to the changing pattern of antimicrobial drug use. [ABSTRACT FROM AUTHOR]

Background: It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined.Methods: To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization.Results: A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval [CI], -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.Conclusions: In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.). [ABSTRACT FROM AUTHOR]

Background: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk., Methods: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis., Results: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%., Conclusions: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background & Aims: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century., Methods: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries., Results: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence)., Conclusions: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Artificial intelligence (AI)-assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an asymptomatic population are lacking., Methods: This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45-75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist's experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393)., Results: From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P < .001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P < .001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P < .001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group., Conclusions: In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Evidence of prophylactic clipping is inconsistent except for proximal and large colonic lesions in the general population. Although warfarin and direct oral anticoagulants (DOACs) are significant risk factors of postpolypectomy bleeding (PPB), dedicated studies to examine the benefit of prophylactic clipping in these high-risk patients remain limited., Methods: We performed a propensity score-weighted retrospective cohort study from 2012 to 2020. Patients who received an oral anticoagulant and underwent colonoscopic polypectomy were included. Data were collected on baseline demographics, medications (anticoagulant, antiplatelet, and heparin bridging), and endoscopies (polyp number, location, size, morphology, histopathology, resection method and prophylactic clipping). Propensity-score models with inverse probability of treatment weighting were developed between prophylactic clipping and no clipping groups. Unbalanced variables were included in a doubly robust model with multivariate analysis. The primary outcome was clinically significant delayed PPB, defined as a composite endpoint of hemoglobin drop ≥2 g/dL, blood transfusion, or repeat colonoscopy for hemostasis within 30 days., Results: Five hundred forty-seven patients with 1485 polyps were included. Prophylactic clipping was not associated with a reduced risk of PPB (odds ratio [OR], 1.19; 95% confidence interval [CI], .73-1.95; P = .497). The hot resection method was associated with a significantly higher risk of PPB (OR, 9.76; 95% CI, 3.94-32.60; P < .001) compared with cold biopsy or snare polypectomy. In a subgroup analysis, prophylactic clipping was associated with a lower PPB risk in patients on DOACs (OR, .36; 95% CI, .16-.82; P = .015)., Conclusions: Prophylactic clipping was not associated with an overall reduced risk of PPB in patients on oral anticoagulants. The use of cold snare polypectomy should be maximized in anticoagulated patients., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century., Methods: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models., Results: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021., Discussion: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum., (Copyright © 2022 by The American College of Gastroenterology.)

Background & Aims: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century., Methods: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD., Results: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous., Conclusions: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Although there are international guidelines on the management of antithrombotic therapy in patients undergoing colonoscopic polypectomy, whether clinicians and patients follow these recommendations are largely unknown. We aimed to evaluate clinician adherence and patient compliance to periendoscopic management of antithrombotic therapy and their impact on clinical outcomes., Methods: Consecutive patients on antithrombotic therapy scheduled for elective colonoscopy in a tertiary referral center were recruited prospectively. Demographic data, indications and periprocedural management of antithrombotic drugs, colonoscopy findings, postpolypectomy bleeding, and serious cardiovascular events were collected systematically. We used Joint Asian Pacific Association of Gastroenterology-Asian Pacific Society for Digestive Endoscopy Practice Guidelines 2018 and assumed clinicians should hold antithrombotics for polypectomy in all colonoscopy patients. Patient compliance was assessed by checking whether discontinuation and resumption of antithrombotic drugs were in accordance with clinician advice., Results: Between December 2017 and October 2019, there were 602 patients recruited who were on antithrombotic drugs undergoing colonoscopy with polypectomy. A total of 98.4%, 41.2%, and 40.0% of clinicians adhered to the guidelines for aspirin alone, clopidogrel alone, and dual-antiplatelet therapy, respectively. Adherence rates were 8.5% for warfarin and 5.2% for direct oral anticoagulants. Compliance to instructions for aspirin alone, clopidogrel alone, dual-antiplatelet therapy, warfarin, and direct oral anticoagulants were achieved in 74.8%, 41.2%, 0%, 36.2%, and 17.5% of patients, respectively. Clinician nonadherence to guidelines was a risk factor for delayed postpolypectomy bleeding (adjusted hazard ratio, 3.54; 95% CI, 1.46-8.58; P = .005), and serious cardiovascular events (hazard ratio, 15.63; 95% CI, 1.83-133.80; P = .012)., Conclusions: Physician adherence to the guideline and patient compliance, with the exception of aspirin, were poor and contributed to adverse clinical outcomes. ClinicalTrials.gov number: NCT03363061., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD., Methods: Proteus spp abundance was assessed by ure gene-specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice., Results: Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice., Conclusions: P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)