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.

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.

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.

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study.

Background: Gender differences existed in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear. Method: Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation. Results: E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046). Conclusion: Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.

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.

Inflammatory Bowel Diseases and Non-Alcoholic Fatty Liver Disease: Piecing a Complex Puzzle Together.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are systemic and multifaceted disorders which affect other organs in addition to the gastrointestinal tract in up to 50% of cases. Extraintestinal manifestations may present before or after IBD diagnosis and negatively impact the intestinal disease course and patients' quality of life, often requiring additional diagnostic evaluations or specific treatments. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Current evidence shows an increased prevalence of NAFLD (and its more advanced stages, such as liver fibrosis and steatohepatitis) in IBD patients compared to the general population. Many different IBD-specific etiopathogenetic mechanisms have been hypothesized, including chronic inflammation, malabsorption, previous surgical interventions, changes in fecal microbiota, and drugs. However, the pathophysiological link between these two diseases is still poorly understood. In this review, we aim to provide a comprehensive overview of the potential mechanisms which have been investigated so far and highlight open issues still to be addressed for future studies.

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.

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.

Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish Nationwide Cohort Study.

BACKGROUND: There are conflicting data on the risk of acute coronary syndrome (ACS) in patients with inflammatory bowel disease (IBD). Only a few previous reports include patients diagnosed during the last decade. AIM: To assess and compare the risk of ACS between patients with IBD and the general population. METHODS: In this cohort study, we used nationwide registers to identify patients diagnosed with IBD in Sweden 2003-2021. Every patient was matched by birth year, sex, calendar year and area of residence with up to 10 general population comparators. The primary outcome was incident ACS. We used semi-parametric Cox proportional hazard models to estimate hazard ratios (HRs). RESULTS: We identified 76,517 patients with IBD (Crohn's disease [CD], N = 22,732; ulcerative colitis [UC], N = 42,194 and IBD-unclassified, N = 11,591) and 757,141 comparators. During a median follow-up of 8 years, 2546 patients with IBD (37.5/10,000 person-years) were diagnosed with ACS compared with 19,598 (28.0/10,000 person-years) among comparators (HR 1.30; 95% confidence interval 1.24-1.35) after adjustments for confounding factors, and approximately one extra case of ACS in 100 IBD patients followed for 10 years. The highest HRs for ACS were in patients with elderly onset IBD (≥60 years) and among patients with CD or UC with extra-intestinal manifestations. No increased HRs were observed in patients diagnosed with IBD before the age of 40. CONCLUSION: In this contemporary cohort of patients with IBD, exposed to modern IBD care, there was an increased risk for ACS compared with individuals from the general population.

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.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

Dermatologic manifestations in pediatric patients with inflammatory bowel disease.

BACKGROUND: Despite studies of dermatologic manifestations in adults with inflammatory bowel disease (IBD), little is known about the prevalence of IBD-associated skin lesions and their correlation with IBD severity in children. We aimed to address these knowledge gaps in our single-center cohort of children with IBD. METHODS: Retrospective chart review of 528 children and adolescents (≤18 years old) with IBD and seen at Mayo Clinic (Rochester, MN) between 1999 and 2017 was conducted. The Chi-Square/Fischer's exact test (with p ≤ .05 to signify statistical significance) was applied to compare categorical outcomes between Crohn's disease (CD) and ulcerative colitis (UC) patients. RESULTS: In total, 425 IBD patients (64.9% CD, 53% males) and ≥1 dermatologic diagnosis were included. Presence of ≥1 cutaneous infection was recorded in 42.8% of participants. Acne was the most common non-infectious dermatologic condition (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%). Angular cheilitis (p = .024), keratosis pilaris (KP, p = .003), and perianal skin complications (i.e., skin tags, fistula, and abscesses; all p < .001) were more frequently diagnosed among children with CD, while fungal skin infections (p = .017) were more frequently diagnosed in UC patients. Severity of IBD correlated with higher prevalence of perianal fistula (p = .003), perianal abscess (p = .041), psoriasis (p < .001), and pyoderma gangrenosum (PG, p = .003). CONCLUSIONS: Both IBD-specific and IBD-nonspecific dermatologic conditions are very prevalent in childhood IBD, the most common being infectious. Children with CD are more likely to experience angular cheilitis, KP, and perianal skin findings than those with UC. Perianal disease, psoriasis, and PG are associated with more severe IBD.

Challenges in the diagnosis and treatment of inflammatory bowel disease in Latin America.

The incidence and prevalence of inflammatory bowel disease (IBD), namely Crohn's disease and ulcerative colitis, have increased in Latin America over the past few decades. Although incidence is accelerating in some countries in the region, other areas in Latin America are already transitioning into the next epidemiological stage-ie, compounding prevalence-with a similar epidemiological profile to the western world. Consequently, more attention must be given to the diagnosis and management of IBD in Latin America. In this Review, we provide an overview of epidemiology, potential local environmental risk factors, challenges in the management of IBD, and limitations due to the heterogenity of health-care systems, both public and private, in Latin America. Unresolved issues in the region include inadequate access to diagnostic resources, biological therapies, tight disease monitoring (including treat to target therapy, surveillance and prevention of complications, drug monitoring), and specialised IBD surgery. Local guidelines are an important effort to overcome barriers in IBD management. Advancements in long-term health-care policies will be important to promote early diagnosis, access to new treatments, and improvements in research in Latin America. These improvements will not only affect overall health care but will also lead to optimal prioritisation of IBD-related costs and resources and enhance the quality of life of people with IBD in Latin America.

Global trends and hotspots of ulcerative colitis based on bibliometric and visual analysis from 1993 to 2022.

Ulcerative colitis (UC) has seen a significant increase over the past 3 decades. However, our understanding of its etiology, pathogenesis, and pharmacological treatment remains limited. This comprehensive review aims to address these gaps by analyzing trends, evaluating previous research, and providing insights for future investigations. We conducted a bibliometric analysis of UC-related papers indexed in the Web of Science from 1993 to 2022. The author, organization, country, and keyword networks in the field of UC were visualized. A total of 36,483 papers were included, showing a continuous upward trend. Most research on UC was conducted in universities, with hospitals leading in high-quality studies. The United States emerged as the primary contributor, followed by China and the United Kingdom. The overall quality of UC-related publications improved, indicating sustained interest in the field. The keywords related to UC was classified into 9 clusters. Keywords detection revealed that UC research focused mainly on the discovery of its etiology and exploration of treatment methods, with research directions evolving from initial treatment of UC and related diseases to clinical trials of UC and subsequently incorporating genomics and bioinformatics techniques to study UC and explore new therapeutic methods and drugs, including recent advances in gut microbiota. Our study identified gaps in understanding the etiology, pathogenesis, and treatment of UC. Future research in UC should focus on genomics, personalized treatment, microbial therapy and leveraging machine learning and artificial intelligence. These areas hold the potential for improving UC diagnosis, treatment, and management.

Adverse Food Reactions in Inflammatory Bowel Disease: State of the Art and Future Perspectives.

Limited knowledge is available about the relationship between food allergies or intolerances and inflammatory bowel disease (IBD). Clinicians frequently encounter patients who report food allergies or intolerances, and gastroenterologists struggle distinguishing between patients with organic disorders and those with functional disorders, which the patients themselves may associate with specific dietary components. This task becomes even more arduous when managing patients with significant underlying organic conditions, like IBD. The aim of this review is to summarize and emphasize any actual associations between food allergies and intolerances and inflammatory diseases, such as ulcerative colitis and Crohn's disease. Through a narrative disceptation of the current literature, we highlight the increased prevalence of various food intolerances, including lactose, fructose, histamine, nickel, and non-celiac gluten sensitivity, in individuals with IBD. Additionally, we explore the association between increased epithelial barrier permeability in IBD and the development of food sensitization. By doing so, we aim to enhance clinicians' awareness of the nutritional management of patients with IBD when facing complaints or evidence of food allergies or intolerances.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort.

BACKGROUND & AIMS: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.

Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations.

Background: Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods: Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results: In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions: Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.

Comprehensive assessment of nutritional and functional status of patients with ulcerative colitis and their impact on quality of life.

INTRODUCTION: Patients with ulcerative colitis (UC) are likely to have poor nutritional intake and increased gut losses. This study was designed to study the prevalence and predictors of nutritional deficiencies in patients with UC and their impact on the quality of life (QOL). METHODS: A prospective study was conducted among consenting patients with UC (cases) and healthy relatives of the cases (controls) visiting a university teaching hospital. They were assessed for clinical, demographic, endoscopic (Mayo score) and histological profile (Robart's score). They were assessed for the presence of macronutrient and micronutrient deficiency, anthropometry, functional status (muscle strength by dynamometer and sit-to-stand test) and the quality of life (short inflammatory bowel disease questionnaire [SIBDQ]). A SIBDQ score of ≤ 50 was considered poor QOL. RESULTS: We studied 126 cases and 57 healthy controls (age [mean ± SD] 37.7 ± 13.2 years vs. 34.40 ± 11.05 years; [p = 0.10] females [38.1% vs. 38.7%]; p = 0.94). Cases more often were underweight (28% vs. 3.5%; p < 0.001), had low mid arm circumference (45% vs. 12%; p < 0.0001), lower functional status in the form of weaker hand grip strength (67% vs. 45.6%; p = 0.007) and weaker lower limb strength (80% vs. 42%; p < 0.0001). Cases more often had the evidence of macronutrient deficiencies: total serum protein deficiency (31% vs. 3.5%; p < 0.0001), serum albumin deficiency (25.4% vs. 0.00%; p < 0.0001) and cholesterol deficiency (63% vs. 28%; p < 0.0001). Micronutrient deficiencies were highly prevalent among cases: calcium (44%), phosphate (21%), magnesium (11%), zinc (76%), iron (87%), folate (16%), vitamin B12 (10%) and vitamin D (81%). Most cases had a poor quality of life (85/126; 67.5%). Factors associated with poor QOL were low hemoglobin, serum albumin, zinc and vitamin D levels and histologically active disease. On multi-variate analysis, low vitamin D levels (odds ratio [OR] = 6.1; 95% confidence interval [CI]: 1.9-19.7) and histologically active disease (OR = 4.0; 95% CI: 1.6-9.9) were identified as independent predictors of poor QOL. CONCLUSIONS: Macronutrient deficiency, micronutrient deficiency, lower functional status and poorer QOL are highly prevalent among patients with UC. The independent predictors of poor QOL were histologically active disease and low serum vitamin D levels. Identifying and correcting the deficiencies may help in improving the QOL of patients with UC.