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Environmental and lifestyle factors play an important role in the natural history of Crohn's disease and ulcerative colitis. A group of international experts from the International Organization for the Study of Inflammatory Bowel Diseases voted on a series of consensus statements to inform the management of inflammatory bowel disease (IBD). The recommendations include avoiding traditional cigarette smoking in patients with Crohn's disease or ulcerative colitis, screening for symptoms of depression, anxiety, and psychosocial stressors at diagnosis and during flares (with referral to mental health professionals when appropriate), and encouraging regular physical activity as tolerated. Patients using dietary approaches for treatment of their IBD should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. We recommend formal assessment for obesity and nutritional deficiencies, and patients should be encouraged to maintain a normal body-mass index. A shared decision-making approach to contraception should include the consideration of IBD-related factors, and risk factors for venous thromboembolism. Long-term or frequent use of high-dose non-steroidal anti-inflammatory drugs should be avoided. For primary prevention of disease in the offspring of patients with IBD, we recommend avoiding passive exposure to tobacco, using antibiotics judiciously, and considering breastfeeding when able.

The appendix is thought to have a role in the pathogenesis of ulcerative colitis, but the nature and basis of this association remains unclear. In this Perspective, we consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to evidence that supports the involvement of the appendix in ulcerative colitis. In experimental models, removal of the inflamed appendix prevents colitis, and in human observational studies, appendectomy is associated with protection against ulcerative colitis. Further, among people who develop ulcerative colitis, appendectomy before diagnosis might influence the course and outcomes of the disease - some evidence suggests that it protects against colectomy but could increase the risk of colorectal cancer. Appendectomy after onset of ulcerative colitis seems to have disparate consequences. Clinical trials to understand whether appendectomy has a role in the treatment of ulcerative colitis are ongoing. Major questions about the role of the appendix in the pathogenesis of ulcerative colitis remain unanswered, and further research is needed to establish whether the connection is clinically relevant. The appendix is thought to have a role in the pathogenesis of ulcerative colitis, but the nature and basis of this association remains unclear. In this Perspective, we consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to evidence that supports the involvement of the appendix in ulcerative colitis. In experimental models, removal of the inflamed appendix prevents colitis, and in human observational studies, appendectomy is associated with protection against ulcerative colitis. Further, among people who develop ulcerative colitis, appendectomy before diagnosis might influence the course and outcomes of the disease - some evidence suggests that it protects against colectomy but could increase the risk of colorectal cancer. Appendectomy after onset of ulcerative colitis seems to have disparate consequences. Clinical trials to understand whether appendectomy has a role in the treatment of ulcerative colitis are ongoing. Major questions about the role of the appendix in the pathogenesis of ulcerative colitis remain unanswered, and further research is needed to establish whether the connection is clinically relevant.

BackgroundThere is an increasing incidence of inflammatory bowel disease (IBD) for which environmental factors are suspected. Antibiotics have been associated with development of IBD in earlier generations, but their influence on IBD risk in adults is uncertain.ObjectiveTo assess the impact of antibiotic exposure, including dose–response, timing and antibiotic class, on the risk of IBD in all individuals aged ≥10 years.DesignUsing Denmark nationwide registries, a population-based cohort of residents aged ≥10 years was established between 2000 and 2018. Incidence rate ratios (IRRs) for IBD following antibiotic exposure were calculated using Poisson regression.ResultsThere were a total of 6 104 245 individuals, resulting in 87 112 328 person-years of follow-up, and 52 898 new cases of IBD. Antibiotic exposure was associated with an increased risk of IBD as compared with no antibiotic exposure for all age groups, although was greatest among individuals aged 40–60 years and ≥60 years (age 10–40 years, IRR 1.28, 95% CI 1.25 to 1.32; age 40–60 years, IRR 1.48, 95% CI 1.43 to 1.54; age ≥60 years, IRR 1.47, 95% CI 1.42 to 1.53). For all age groups a positive dose–response was observed, with similar results seen for both ulcerative colitis and Crohn’s disease. The highest risk of developing IBD was seen 1–2 years after antibiotic exposure, and after use of antibiotic classes often prescribed to treat gastrointestinal pathogens.ConclusionAntibiotic exposure is associated with an increased risk of IBD, and was highest among individuals aged 40 years and older. This risk increased with cumulative antibiotic exposure, with antibiotics targeting gastrointestinal pathogens and within 1–2 years after antibiotic exposure.

BACKGROUND: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS: This was a multi-center cross-sectional study performed at five academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected and the inflammatory bowel disease disability index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI≥35) were assessed in univariable and multivariable models. RESULTS: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared to patients with medically managed UC (29.8 vs 17.9, p

Purpose of Review: Crohn’s Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, “top-down” biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20–30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. Recent Findings: For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn’s Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. Summary: The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.

The epidemiology of inflammatory bowel disease (IBD) has undergone considerable shifts since its emergence in the Western world over a century ago, especially in the last few decades, with increasing global burden of disease. IBD incidence continues to rise in developed countries in all age groups which is contributing to compounding prevalence. Further, IBD incidence is rising sharply in Asia and other recently developed and developing countries. In this review, we discuss the implications of changing trends of IBD epidemiology. First, changing patterns provide insights into IBD causes, as they occur concurrent with shifts in the environment, cultures, and attitudes. Understanding the impact of the environment on IBD risk can help towards prediction and prevention strategies. Second, we must prepare healthcare systems for the rising burden of IBD and address it at various levels towards improving outcomes and health, overall.

© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Over the recent years, increasing evidence has strengthen the concept that inflammatory bowel disease (IBD) diagnosis is preceded by dysregulated immune pathways, altered intestinal permeability, dysbiosis, and other pathogenic mechanisms, that set the stage for disease to become clinically manifest. Understanding this preclinical period1 can help deconvolute IBD pathogenesis, lead to prediction tools, novel therapeutic strategies, and preventive interventions., MA is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129762-02).

Background and Aims Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age. Methods We included IBD patients diagnosed with COVID-19, reported to SECURE-IBD between March 13, 2020 and August 3, 2021. Clinical IBD activity was measured by physician global assessment [PGA]. COVID-19-related outcomes were [1] intensive care unit [ICU] admission, ventilation or death, and [2] hospitalization. Using generalized estimating equations, we determined adjusted odds ratios [aOR, 95% confidence interval] for moderate and severe PGA vs clinical remission/mild PGA, controlling for demographics, medications and COVID-19 diagnosis period. We performed stratified analyses by age [≤50 vs >50 years]. Results Among 6078 patients, adverse COVID-19 outcomes were more common with active IBD: ICU/ventilation/death in 3.6% [175/4898] of remission/mild, 4.9% [45/920] of moderate and 8.8% [23/260] of severe [p < 0.001]; and hospitalization in 13% [649/4898] of remission/mild, 19% [178/920] of moderate and 38% [100/260] of severe [p < 0.001]. Stratified by decade, effect sizes were larger for younger patients. In patients ≤50 years, severe PGA was independently associated with ICU/ventilation/death (aOR 3.27 [1.15–9.30]) and hospitalization (aOR 4.62 [2.83–7.55]). In contrast, severe PGA was not independently associated with COVID-19 outcomes in those older than 50 years. Conclusions Clinically active IBD may be a risk factor for severe COVID-19, particularly in younger patients. IBD disease control, including through medication compliance, and strategies to mitigate the risk of COVID-19 infection amongst patients with active IBD [e.g. distancing, immunization] are key to limit adverse COVID-19 outcomes.

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn’s disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients’ concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.

Worldwide elderly people are being affected by diabetes mellitus (DM) and dementia. The risk for the development of dementia is higher in people with DM. DM causes a marked cognitive reduction and increases the risk of dementia, most commonly vascular dementia and Alzheimer's disease. People affected by DM and dementia seem to be at higher risk for intense hypoglycemia. Hypoglycemia, the complication of DM treatment, is believed as an independent risk factor for dementia in people with DM. Both Alzheimer's disease and DM are linked with decreased insulin secretion, reduced uptake of glucose, raised oxidative stress, angiopathy, activation of the apoptotic pathway, aging, abnormal peroxidation of lipids, increased production of advanced glycation end products and tau phosphorylation, brain atrophy, and decreased fat metabolism. In this paper, we will review the association between Alzheimer's disease and DM. In addition, we will discuss the agents that enhance the risk for dementia in elderly people with DM and how to prevent the development of cognitive dysfunction in DM.

Background Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC). Methods We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis. Results Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment—Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment—Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31–0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27–0.83), and clinical response (aOR, 0.51; 95% CI, 0.29–0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15–0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials. Conclusions Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.

OBJECTIVE: There are limited data on the impact of coronavirus disease 2019 (COVID-19) on hospitalized patients with autoimmune and chronic inflammatory disease (AICID) compared with patients who do not have AICID. We sought to evaluate whether patients with AICID who have confirmed COVID-19 presenting to the hospital are at higher risk of adverse outcomes compared with those patients without AICID who are infected with COVID-19 and whether immunosuppressive medications impact this risk. METHODS: We performed a multicenter retrospective cohort study with patients presenting to five hospitals in a large academic health system with polymerase chain reaction-confirmed COVID-19 infection. We evaluated the impact of having an AICID and class of immunosuppressive medication being used to treat patients with AICID (biologics, nonbiologic immunosuppressives, or systemic corticosteroids) on the risk of developing severe COVID-19 defined as requiring mechanical ventilation (MV) and/or death. RESULTS: A total of 6792 patients with confirmed COVID-19 were included in the study, with 159 (2.3%) having at least one AICID. On multivariable analysis, AICIDs were not significantly associated with severe COVID-19 (adjusted odds ratio [aOR] 1.3, 95% confidence interval [CI]: 0.9-1.8). Among patients with AICID, use of biologics or nonbiologic immunosuppressives did not increase the risk of severe COVID-19. In contrast, systemic corticosteroid use was significantly associated with an increased risk of severe COVID-19 (aOR 6.8, 95% CI: 2.5-18.4). CONCLUSION: Patients with AICID are not at increased risk of severe COVID-19 with the exception of those on corticosteroids. These data suggest that patients with AICID should continue on biologic and nonbiologic immunosuppression but limit steroids during the COVID-19 pandemic.

BACKGROUND & AIMS: Shifts in epidemiological stages of inflammatory bowel disease (IBD) carry implications toward understanding IBD etiology and managing clinical care. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2016 in the Danish nationwide cohort.METHODS: We used the Danish registers to obtain data on demographics and IBD-related outpatient and inpatient contacts between 1995 and 2016. IBD diagnosis was defined as having ≥2 registrations related to Crohn's disease (CD) or ulcerative colitis (UC) within a 2-year period. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex.RESULTS: A total of 47,830 individuals met the criteria for IBD diagnosis, of which 33% were diagnosed with CD and 67% with UC. Between 1995 and 2016, the incidence rate (95% confidence interval) per 100,000 person-years rose from 9.1 (8.3-10.0) to 17.8 (16.8-19.0) for CD, and from 21.0 (19.8-22.3) to 28.4 (27.0-29.8) for UC. The highest increase in CD and UC incidence rates occurred in children and young adults, respectively. The prevalence of IBD doubled from 1995 to 2016; the greatest increase (2.5-fold) was in UC prevalence among individuals aged >40 years. During this period, the median age of the IBD population increased by 6 to 7 years.CONCLUSIONS: In Denmark, the incidence and prevalence of IBD have increased during the last 2 decades. The IBD population is shifting toward an older age. These findings have implications towards understanding environmental shifts as well as preparing health care systems for an aging IBD population.

Importance: Because the incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing, knowledge of the long-term risk of cancer in this patient population is required.Objective: To evaluate the relative rate of cancer among patients with pediatric-onset IBD.Data Sources: A comprehensive systematic search was performed of MEDLINE and Embase from the date of database inception to October 31, 2021.Study Selection: All unselected, population-based cohort studies of pediatric-onset IBD assessing the risk of cancer were included. Tertiary center referrals and insurance database studies were excluded. All articles were assessed by 2 independent reviewers.Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for data extraction and used the Newcastle-Ottawa Scale for assessment of the risk of bias and the quality of included articles.Main Outcomes and Measures: A random-effects model meta-analysis was conducted of included studies using the inverse-variance method to assess the relative rate of cancer overall and by IBD subtype (Crohn disease or ulcerative colitis), sex, and thiopurine exposure among patients with pediatric-onset IBD. Pooled relative rates (pRRs) along with 95% CIs were calculated for combined studies.Results: Of 4628 articles screened, 5 population-based studies from North America and Europe were eligible for inclusion. These studies comprised 19 812 individuals with pediatric-onset IBD followed up for 283 540 person-years in which 715 cases of cancer were identified. Meta-analysis of pRR estimates showed a 2.4-fold increased rate of cancer among patients with pediatric-onset IBD (pRR, 2.46; 95% CI, 2.06-2.93), seen among patients with Crohn disease (pRR, 2.03; 95% CI, 1.67-2.46) and those with ulcerative colitis (pRR, 2.61; 95% CI, 2.00-3.40). This increased rate is primarily due to an increased rate of liver (pRR, 55.45; 95% CI, 19.59-156.99), colorectal (pRR, 20.29; 95% CI, 15.90-25.90), and small bowel (pRR, 16.20; 95% CI, 3.52-74.66) cancers. The incidence rate of cancer among patients with pediatric-onset IBD was reported by 4 studies and ranged from 1.0 to 3.3 cases per 1000 person-years.Conclusions and Relevance: This meta-analysis of unselected, population-based studies showed a greater than 2-fold increased rate of cancer among patients with pediatric-onset IBD compared with the general pediatric populations, primarily owing to an increased rate of gastrointestinal cancers.

Inflammatory bowel disease (IBD) is an immune-mediated disease of the intestinal tract, with complex pathophysiology involving genetic, environmental, microbiome, immunological and potentially other factors. Epidemiological data have provided important insights into risk factors associated with IBD, but are limited by confounding, biases and data quality, especially when pertaining to risk factors in early life. Multiomics platforms provide granular high-throughput data on numerous variables simultaneously and can be leveraged to characterize molecular pathways and risk factors for chronic diseases, such as IBD. Herein, we describe omics platforms that can advance our understanding of IBD risk factors and pathways, and available omics data on IBD and other relevant diseases. We highlight knowledge gaps and emphasize the importance of birth, at-risk and pre-diagnostic cohorts, and neonatal blood spots in omics analyses in IBD. Finally, we discuss network analysis, a powerful bioinformatics tool to assemble high-throughput data and derive clinical relevance.

Summary Intake of specific dietary macro- and micronutrients has been implicated in modulating the risk of inflammatory bowel disease (IBD)(Nat Rev Gastroenterol Hepatol 2018;15:525-535). Recent epidemiological and pre-clinical studies have additionally examined the impact of non-nutritional dietary components on IBD. Ultra-processed foods (UPF), as defined by the NOVA classification, are foods of mainly industrial origin, often containing little or no whole foods but many ingredients including food additives such as artificial colors and flavors, stabilizers, emulsifiers, and preservatives(Public Health Nutr 2019;22:936-941). The objective of the study by Narula et al (BMJ 2021;374:n1554) was to examine the association between intake of UPF and the risk of developing IBD.

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Inflammatory bowel disease has a high incidence and prevalence especially in young individuals in their reproductive years. Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. Therefore, the management of patients with a wish to conceive and during pregnancy requires specialized counselling and appropriate management including a multidisciplinary approach and close involvement of the prospective parents under a shared decision-making model. This updated consensus paper addresses these issues and is aimed to optimize pre-conceptional, pregnancy and post pregnancy counselling, including the monitoring and therapeutic management of patients with IBD patients with a wish to conceive. ispartof: JOURNAL OF CROHNS & COLITIS vol:17 issue:1 pages:1-27 ispartof: location:England status: published

Background Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients. Methods The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021. Results Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, −5.3% to −3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, −7.8% to −4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, −8.1%; 95% CI, −15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, −8.5%; 95% CI, −10.2 to −6.7) and Europe (APC, −5.4%; 95% CI, −7.2 to −3.6) and was stable in Latin America (APC, −1.5%; 95% CI, −3.5% to 0.6%). Conclusions Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally.

Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.

ObjectiveOur objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes.DesignUsing national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn’s disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark.ResultsAmong 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants.ConclusionRelative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.

Janus kinase inhibitors [JAKi] are a new class of small molecule drugs that modulate inflammatory pathways by blocking one or more JAK receptors, and are increasingly being used in the treatment of immune-mediated diseases. Tofacitinib, a non-selective JAKi, is now approved for moderate-to-severe ulcerative colitis [UC] that is refractory or intolerant to tumour necrosis factor inhibitors [TNFi]. Whereas tofacitinib is associated with the advantages of oral administration, rapid onset of action, and lack of immunogenicity over TNFi, there are many safety considerations to take into account such as the risk of thromboembolism, infections, and hyperlipidaemia: each with specific nuances pertaining to prevention and monitoring strategies. Considerations such as pregnancy, breastfeeding, and history of malignancy also are to be navigated with utmost caution, given that very few data are available for guidance. With the use of JAKi in the real world progressively over time, safety implications will become more lucid, including caveats pertaining to JAK selectivity and gut-selective JAKi, as well as mechanistic data pertaining to adverse effects. This Viewpoint serves as a practical guide for clinicians managing inflammatory bowel disease [IBD] patients to navigate safety concerns around JAKi, including preventive and monitoring strategies.

Fatigue is a burdensome, multidimensional, and multifactorial symptom that is associated with a wide array of chronic illnesses, specifically occurring in nearly 50% of patients with inflammatory bowel disease (IBD). Although common, given its subjective nature, physicians often under-recognize and undertreat this debilitating symptom. There are multiple etiologies that can contribute to fatigue in patients with IBD, including disease activity, anemia, medications, psychosomatic symptoms, and alterations to the gut-brain axis. The management of fatigue in IBD can be challenging, as it is often times multifaceted. In this review, we summarize the available tools for the diagnosis and measurement of fatigue, discuss etiologies, and make recommendations for their management. We identify knowledge gaps for the workup and treatment of fatigue and propose an algorithm to aid physicians in the evaluation and management of fatigue in this unique population. However, future research is needed to address several areas of knowledge deficits and improve the management of fatigue in IBD.

ObjectivesDevelop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).Design and settingThis study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March–15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September–20 October 2020).ParticipantsWe included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included.Primary and secondary outcome measuresCOVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models’ discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs.ResultsOf the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk.ConclusionsPrognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.

BACKGROUND: Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk after ASUC between Korea and the USA. METHODS: Data on patients admitted for ASUC to five tertiary referral hospitals in Korea and Mount Sinai Hospital, New York, the USA, between January 2015 and January 2019 were reviewed retrospectively. For comparability between groups, a 1:1 propensity score matching (PSM) was performed. The primary outcome was colectomy, and secondary outcomes were mortality, readmission, and venous thromboembolism (VTE) within 1-year of the index admission for ASUC. The risk of each outcome was compared using Cox proportional hazards model in pre-matched cohort and Kaplan–Meier analysis with log-rank test in post-matched cohort. RESULTS: 290 ASUC patients were included in the study (121 Korea, 169 the USA). After PSM, 56 patients were selected in each group with no significant differences in baseline variables. At 1 year after ASUC, colectomy was less common in Korea than in the USA [3 (5.4%) vs. 24 (42.9%), p < 0.001]. The cumulative colectomy risk was significantly higher in the USA than in Korea in pre-matched cohort [adjusted hazard ratio 7.89, 95% confidence interval 3.23 to 19.22] and in post-matched cohort (log-rank p < 0.001), while there was no difference in cumulative risk of mortality, readmission, and VTE. CONCLUSION: Colectomy risk within 1 year of ASUC is significantly higher in the USA than in Korea. We observed no differences in mortality, readmission, and VTE between the two groups.

Patients with immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) on immunosuppressive and biologic therapies were largely excluded from severe acute respiratory syndrome coronavirus-2 messenger RNA vaccine trials.We evaluated adverse events (AE) after messenger RNA vaccination in 246 adults with IBD participating in a longitudinal vaccine registry.In general, AE frequency was similar to that reported in the general population. AEs were more common among younger patients and those with previous COVID-19. AEs were less common in individuals receiving advanced therapies with biologics or small-molecule inhibitors.Those with IBD and other immune-mediated inflammatory diseases can be reassured that the AE risk is likely not increased, and may be reduced, while on advanced therapies.

BACKGROUND There are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population. METHODS Data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death. RESULTS Among 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids. CONCLUSION In patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.

BACKGROUND: Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri‑, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. METHODS: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. FINDINGS: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2-2.5) and tobacco smoke (OR 1.5; 95% CI 1.2-1.9), and early life otitis media (OR 2.1; 95% CI 1.2-3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. INTERPRETATION: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. FUNDING: This study did not receive any funding. ispartof: ECLINICALMEDICINE vol:36 ispartof: location:England status: published

Mother-to-child transmission of Helicobacter pylori (H. pylori) is the primary source of intrafamilial spread in early childhood in regions of high H. pylori prevalence. However, early-in-life H. pylori colonization and associated protective or risk factors have not been fully evaluated in lower prevalence regions, such as the USA.Therefore, from a well-characterized prospective US cohort, we selected women who provided fecal samples during pregnancy and had paired fecal samples from their babies up to 24 months postpartum. We evaluated maternal and baby factors associated with likelihood of H. pylori colonization in the babies. Fecal antigen testing was used to determine H. pylori status. We also evaluated the association between maternal breastmilk cytokines and H. pylori colonization in breastfed babies.Among included mother-baby pairs (n = 66), H. pylori prevalence was 31.8% in mothers and 19.7% in their babies. Dominant breastfeeding (adjusted odds ratio [aOR] 0.17, 95% CI 0.03-0.98) and maternal IBD (aOR 0.05, 95% CI 0.01-0.27) were associated with significantly lower likelihood of H. pylori colonization among babies; no other clinical factors were associated with H. pylori colonization in the babies. Matrix metalloproteinase-10 (MMP-10) and tumor necrosis factor-related activation-induced cytokine expression were significantly higher in breastmilk of mothers with H. pylori positive vs negative babies.Consistent with data from high H. pylori prevalence regions, our findings suggest dominant breastfeeding may protect against early H. pylori colonization. Downregulation of pro-inflammatory cytokines such as MMP-10 may be relevant in mediating this protection among breastfed babies, but more data are needed.

Background The impact of immune-modifying therapies on outcomes of coronavirus disease 2019 [COVID-19] is variable. The purpose of this study was to determine the impact of vedolizumab [VDZ], a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease [IBD] patients. Methods Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD [SECURE-IBD], an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 [intensive care unit stay, mechanical ventilation and/or death]. Results Of 3647 adult patients on any IBD medication in the registry, 457 [12.5%] patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when compared with patients on all other medications (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI] 0.71, 1.1 and aOR 0.95; 95% CI 0.53, 1.73, respectively). On comparing VDZ monotherapy to anti-tumour necrosis factor [anti-TNF] monotherapy, the odds for hospitalization, but not severe COVID-19, were higher [aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively]. In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset gastrointestinal symptoms at the time of COVID-19, especially among patients whose IBD was in remission. Conclusions COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19.

Inflammatory bowel diseases, including Crohn disease (CD) and ulcerative colitis (UC), are chronic, progressive, immune-mediated inflammatory diseases of the gastrointestinal tract. Early therapy using a treat-to-target (T2T) approach, which implies identification of a pre-defined target, followed by optimization of therapy and regular monitoring until the goal is achieved is critical in preventing adverse long-term outcomes. In this review, the authors discuss the T2T guidance developed by the Selecting Therapeutic Targets in Inflammatory Bowel Disease committee, new evidence published on the role of various targets in CD and UC, as well as the real-world applicability of T2T."

BACKGROUND Race, ethnicity and socio-economic status impact clinical outcomes in inflammatory bowel disease (IBD) patients. However, their impact on disability has not been studied. AIM To determine the association between race, ethnicity and socio-economic factors with disability in IBD, using the validated IBD disability index (IBD-DI). METHODS Ambulatory IBD patients were enrolled at five academic centres participating in the New York Crohn's and Colitis Organization. We assessed the IBD-DI, and collected clinical and socio-economic data. Factors associated with moderate-to-severe disability (IBD-DI score > 35) on univariable analysis were tested in multivariable models with adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported. RESULTS In this study, 323 patients (57.3% CD, 51.4% female) were enrolled; 17.7% were Hispanic, 17% were non-Hispanic black, 56.0% were non-Hispanic Caucasian and 9.3% belonged to non-Hispanic non-black minority races. However, 39.0% of patients were publicly insured and 38.4% of patients had low annual household income (