[Phenotyping and genotyping in patients with inflammatory bowel disease in a reference center in Colombia]. / Fenotipificación y genotipificación en pacientes con enfermedad inflamatoria intestinal en un centro de referencia de Colombia.

INTRODUCTION: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. OBJECTIVE: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. MATERIALS AND METHODS: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multi-gene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. RESULTS: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). CONCLUSION: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.

Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.

Background: Eosinophilic esophagitis (EoE) and inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are immune-mediated gastrointestinal diseases with overlapped pathogenesis and are sometimes concurrently diagnosed, but their causal relationship remains unclear. We investigated the causal relationship between EoE and IBD and its subtypes via a two-sample bidirectional Mendelian randomization (MR) approach. Methods: MR analyses were performed using summary data of a genome-wide association study (GWAS) on individuals of European ancestry. Independent single-nucleotide polymorphisms correlated with EoE (from a GWAS meta-analysis containing 1,930 cases and 13,634 controls) and IBD (from FinnGen GWASs containing 9,083 IBD, 2,033 CD, and 5,931 UC cases, and GWASs of IBD genetic consortium containing 12,882 IBD, 6,968 UC, and 5,956 CD cases) were selected as instruments. We applied the inverse variance weighted (IVW) method as the primary analysis followed by several sensitivity analyses. For the forward MR study, estimates from IVW methods were subsequently meta-analyzed using a random-effect model. Results: Our results suggested a causal effect of EoE on IBD [pooled odds ratio (OR), 1.07; 95% confidence interval (CI), 1.02-1.13] and EoE on UC (pooled OR, 1.09, 95% CI, 1.04-1.14). No causal link between EoE and CD was observed (pooled OR, 1.05; 95% CI, 0.96-1.16). The reverse MR analyses revealed no causal effect of IBD (and its subtypes) on EoE. Sensitivity analyses confirmed the robustness of primary results. Conclusions: Our findings provided evidence of a suggestive causal effect of EoE on IBD (specifically on UC) in the European population. Increased awareness of concurrent or subsequent IBD in patients with EoE is called for. Still, the present evidence is not adequate enough and ought to be validated by further investigations.

Prevalence, incidence, and treatment patterns of fistulizing Crohn disease: A US population-based cohort study.

BACKGROUND: Population-based studies for patients with fistulizing Crohn disease (CD), a severe complication of CD, are limited. OBJECTIVE: To report estimates of the prevalence and incidence rates of fistulizing CD in the United States and examine associated treatment patterns among incident cases. METHODS: This retrospective, observational cohort study used a US administrative claims database from January 1, 2016, to December 31, 2019, with at least 365 days' continuous insurance enrollment. The prevalent patient population comprised patients with incident or existing cases of fistulizing CD. Crude, age, and sex-adjusted prevalence and incidence rates of fistulizing CD were estimated. Baseline characteristics, comorbidities, and CD-related medications and medical procedures were examined for patients with fistulizing CD. RESULTS: The overall crude prevalence (prevalent cases: n = 5,082) and incidence rates (incident cases: n = 2,399) between 2017 and 2019 were 25.2 (95% CI = 24.5-25.9) per 100,000 persons and 6.9 (95% CI = 6.6-7.1) per 100,000 person-years, respectively. Age- and sex-adjusted prevalence and incidence rates were 24.9 (95% CI = 24.2-25.6) per 100,000 persons and 7.0 (95% CI = 6.7-7.3) per 100,000 person-years, respectively. Approximately half of all patients with incident fistulizing CD were prescribed biologic therapies within 1 year of an incident fistula diagnosis, with anti-tumor necrosis factor therapies the most widely prescribed biologic class; antibiotic and corticosteroid use was also common. Among the incident cases, approximately one-third of patients required surgery during the follow-up period, most of which occurred within 3 months of the index date. CONCLUSIONS: This study reports age- and sex-adjusted prevalence and incidence rates for fistulizing CD of 24.9 per 100,000 persons and 7.0 per 100,000 person-years, respectively. As a concerning complication of CD, first-year treatment of fistulas in the United States commonly includes anti-tumor necrosis factor therapy, and there is a considerable surgical burden.

Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Background and objectives: Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. Materials and methods: A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. Results: The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). Conclusion: This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Pediatric stricturing Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract. The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide. Notably, approximately 25% of children with CD develop stricturing CD (SCD) that requires intervention. Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions. Non-pharmacological therapeutic strategies include endoscopic balloon dilatation, stricturoplasty, and surgical resection of the strictured segment. However, strictures tend to recur postoperatively regardless of treatment modality. The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%. Thus, new and emerging strategies, advanced diagnostic tools, and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Pregnancy period and early-life risk factors for inflammatory bowel disease: a Northern Finland birth cohort 1966 study.

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. RESULTS: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70-17.3). Breastfeeding (OR = 0.18, 95% CI 0.08-0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21-0.89) were negatively associated with CD. CONCLUSIONS: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link. OBJECTIVES: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship. METHODS: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors. RESULTS: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls. CONCLUSIONS: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.

Trends in the prevalence and incidence of Crohn's disease in Japan and the United States.

PURPOSE: This study is to describe patient demographic characteristics and estimate annual prevalence and incidence rates of Crohn's disease (CD) in Japan and the United States (US). METHODS: Two large employment-based healthcare claims databases (Japan Medical Data Center [JMDC] in Japan and Merative MarketScan [Merative] in the US) were used to identify patients with CD from 2010 to 2019. Cases were confirmed using an algorithm based on diagnostic with/without treatment codes. The Merative population was used for sex and age standardization of annual prevalence and incidence rates estimated from the JMDC. RESULTS: Patients with CD were generally younger in Japan than in the US at diagnosis (mean 33.6 vs. 39.4 years) and 71.5% were male versus 45.1% in the US. Annual prevalence per 100,000 population increased substantially in both countries, from 34.2 in 2010 to 54.5 in 2019 in Japan (standardized) and 163.3 to 224.2 in the US. Prevalence rates increased in both males and females in all age groups between 6 and < 65 years. Annual incidence rate per 100,000 person-years was almost fourfold higher in the US than Japan (21.0 vs. 5.5 [standardized] in 2019) but remained stable in both countries over time in both sexes and in all age groups. CONCLUSION: The epidemiology of CD differs between Japan and the US. Research to understand the basis of these differences could help to identify at-risk groups in each country, and guide implementation of preventive measures.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Perianal disease: Updates and controversies in closing the gaps.

Perianal complications are common and morbid in children with Crohn's disease. In this review, we describe the epidemiology, the presentation and diagnosis, evaluation and management. We focus on updates such as the increasing frequency of biologic medications and MRI for evaluation. We also highlight controversies on the timing and approaches to surgical techniques. Finally, perianal disease requires the coordination of multidisciplinary care with nursing, radiology, gastroenterology, and surgery to optimize outcomes - both medical and patient-centered.

Latent profiles of fatigue in inflammatory bowel disease.

INTRODUCTION: Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis. METHODS: An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated. RESULTS: In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile. CONCLUSION: Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Inflammatory bowel disease is associated with an increase in the incidence of multiple sclerosis: a retrospective cohort study of 24,934 patients.

BACKGROUND: Recent data suggest a potential pathophysiological link between inflammatory bowel disease (IBD) and multiple sclerosis (MS), two immune-mediated diseases both of which can have a significant impact on patients' quality of life. In the present manuscript, we investigate the association between IBD and MS in a German cohort of general practice patients. These results may have important implications for the screening and management of patients with IBD, as well as for further research into the pathophysiological mechanisms underlying both disorders. METHODS: 4,934 individuals with IBD (11,140 with Crohn's disease (CD) and 13,794 with ulcerative colitis (UC)) as well as 24,934 propensity score matched individuals without IBD were identified from the Disease Analyzer database (IQVIA). A subsequent diagnosis of MS was analyzed as a function of IBD using Cox regression models. RESULTS: After 10 years of follow-up, 0.9% and 0.7% of CD and UC patients but only 0.5% and 0.3% of matched non-IBD pairs were diagnosed with MS, respectively (pCD = 0.002 and pUC < 0.001). Both CD (HR: 2.09; 95% CI 1.28-3.39) and UC (HR: 2.35; 95% CI 1.47-3.78) were significantly associated with a subsequent MS diagnosis. Subgroup analysis revealed that the association between both CD and UC and MS was more pronounced among male patients. CONCLUSION: The results of our analysis suggest a notable association between IBD and a subsequent MS diagnosis. These findings warrant further pathophysiological investigation and may have clinical implications for the screening of IBD patients in the future.

STRUCTURAL EVALUATION OF INFLAMMATORY BOWEL DISEASE COMPREHENSIVE CARE UNITS IN BRAZIL.

BACKGROUND: The most efficient way to prevent complications from inflammatory bowel disease (IBD) is to provide patients with optimized care. Nonetheless, in Brazil, there is no validated methodology for evaluating health services recognized as comprehensive care units (CCU), making it difficult to assess the quality of care provided. OBJECTIVE: To understand the current scenario, map the distribution of centers and identify strengths and weaknesses, considering local and regional characteristics. METHODS: The study was carried out in three phases. Initially, the Brazilian Organization for Crohn's disease and colitis (GEDIIB) developed 22 questions to characterize CCU in Brazil. In the second phase, all GEDIIB members were invited to respond to the survey with the 11 questions considered most relevant. In the last phase, an interim analysis of the results was performed, using the IBM SPSS Statistics v 29.0.1.0 software. Descriptive statistics were used to characterize the center's profile. The chi-square test was used to compare categorical variables. RESULTS: There were 53 responses from public centers (11 excluded). Most centers were concentrated in the Southeastern (n=22/52.4%) and only 1 (2.4%) in the Northern region of Brazil. Thirty-nine centers (92.9%) perform endoscopic procedures, but only 9 (21.4%) have access to enteroscopy and/or small bowel capsule endoscopy. Thirty-three centers (78.6%) offer infusion therapy locally, 26 (61.9%) maintain IBD patient records, 13 (31.0%) reported having an IBD nurse, 34 (81.0%) have specific evidence-based protocols and only 7 (16.7%) have a patient satisfaction methodology. In the private scenario there were 56 responses (10 excluded). There is also a concentration in the Southeastern and Southern regions. Thirty-nine centers (84.8%) have access to endoscopic procedures and 19 perform enteroscopy and/or small bowel capsule endoscopy, more than what is observed in the public environment. Infusion therapy is available in 24 centers (52.2%). Thirty-nine centers (84.8%) maintain a specific IBD patient database, 17 (37%) have an IBD nurse, 36 (78.3%) have specific evidence-based protocols, and 22 (47. 8%) apply a patient satisfaction methodology. CONCLUSION: IBD CCU in Brazil were mainly located in the Southeastern and Southern regions of the country. Most centers have dedicated multidisciplinary teams and IBD specialists. There is still a current need to improve the proportion of IBD nurses in IBD care in Brazil. BACKGROUND: •In Brazil, there is no validated methodology for evaluating health services recognized as comprehensive care units (CCU), making it difficult to assess the quality of care provided. BACKGROUND: •Most CCU were concentrated in the Southeast region and only one (2.4%) in the Northeast region of Brazil. This pattern follows the epidemiological trends of IBD in the country. BACKGROUND: •There is still difficulty in accessing enteroscopy and/or small bowel capsule endoscopy in the public health system. BACKGROUND: •Most centers have dedicated multidisciplinary teams and IBD specialist doctors. BACKGROUND: •There is still a current need to improve the proportion of nurses treating IBD in Brazil.

Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations.

BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear. METHODS: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results. RESULTS: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844-0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000-1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis. CONCLUSIONS: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.

Prognosis of Patients with Crohn's Disease and Ulcerative Colitis Following Percutaneous Coronary Intervention Procedures.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk after percutaneous coronary intervention (PCI). OBJECTIVES: To compare the clinical outcomes within 30 days, one year, and five years of undergoing PCI. METHODS: We conducted a retrospective cohort study of adult patients with IBD who underwent PCI in a tertiary care center from January 2009 to December 2019. RESULTS: We included 44 patients, 26 with Crohn's disease (CD) and 18 with ulcerative colitis (UC), who underwent PCI. Patients with CD underwent PCI at a younger age compared to UC (57.8 vs. 68.9 years, P < 0.001) and were more likely to be male (88.46% of CD vs. 61.1% of UC, P < 0.03). CD patients had a higher rate of non-steroidal treatment compared to UC patients (50% vs. 5.56%, P < 0.001). Acute coronary syndromes (ACS) and/or the need for revascularization (e.g., PCI) were the most common clinical events to occur following PCI, in both groups. Of patients who experienced ACS and/or unplanned revascularization within 5 years, 25% of UC vs. 40% of CD had target lesion failure (TLF) due to in-stent restenosis and 10% of CD had TLF due to stent thrombosis. CONCLUSIONS: We observed higher rates of TLF in IBD patients compared to the general population as well as differences in clinical outcomes between UC and CD patients. A better understanding of the prognostic factors and pathophysiology of these differences may have clinical importance in tailoring the appropriate treatment or type of revascularization for this high-risk group.

Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn's disease (CD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022. ELIGIBILITY CRITERIA: Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1). RESULTS: 11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, χ2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS. CONCLUSIONS: MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS. PROSPERO REGISTRATION NUMBER: CRD42022346340.

Correlation of Socioeconomic and Environmental Factors With Incidence of Crohn Disease in Children and Adolescents: Systematic Review and Meta-Regression.

BACKGROUND: The worldwide incidence of Crohn disease (CD) in childhood and adolescence has an increasing trend, with significant differences between different geographic regions and individual countries. This includes an increase in the incidence of CD in countries and geographic regions where CD was not previously prevalent. In response to the increasing incidence, the pediatric care landscape is facing growing challenges. OBJECTIVE: This systematic review and meta-analysis were undertaken to comprehensively delineate the incidence rates of CD in pediatric populations across different countries and to explore potential influencing factors. METHODS: We performed a systematic review of PubMed and Embase (via Ovid) for studies from January 1, 1970, to December 31, 2019. In addition, a manual search was performed in relevant and previously published reviews. The results were evaluated quantitatively. For this purpose, random effects meta-analyses and meta-regressions were performed to investigate the overall incidence rate and possible factors influencing the incidence. RESULTS: A qualitative synthesis of 74 studies was performed, with 72 studies included in the meta-analyses and 52 in the meta-regressions. The results of our meta-analysis showed significant heterogeneity between the individual studies, which cannot be explained by a sample effect alone. Our findings showed geographical differences in incidence rates, which increased with increasing distance from the equator, although no global temporal trend was apparent. The meta-regression analysis also identified geographic location, UV index, and Human Development Index as significant moderators associated with CD incidence. CONCLUSIONS: Our results suggest that pediatric CD incidence has increased in many countries since 1970 but varies widely with geographic location, which may pose challenges to the respective health care systems. We identified geographic, environmental, and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These results can serve as a basis for future research. To this end, implementations of internationally standardized and interoperable registries combined with the dissemination of health data through federated networks based on a common data model, such as the Observational Medical Outcomes Partnership, would be beneficial. This would deepen the understanding of CD and promote evidence-based approaches to preventive and interventional strategies as well as inform public health policies aimed at addressing the increasing burden of CD in children and adolescents. TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews CRD42020168644; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168644. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-037669.