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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.

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

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.

FMRP is an RNA-binding protein that represses the translation of specific mRNAs. In neurons, its depletion determines the exaggerated translation of mRNAs leading to dendritic and axonal aberrant development, two peculiar features of Fragile X syndrome patients. However, how FMRP binds to translational machinery to regulate the translation of its mRNA targets is not yet fully understood. Here, we show that FMRP localizes on translational machinery by interacting with the ribosomal binding protein, Receptor for Activated C Kinase 1 (RACK1). The binding of FMRP to RACK1 removes the translational repressive activity of FMRP and promotes the translation of PSD-95 mRNA, one specific target of FMRP. This binding also results in a reduction in the level of FMRP phosphorylation. We also find that the morphological abnormalities induced by Fmr1 siRNA in cortical neurons are rescued by the overexpression of a mutant form of RACK1 that cannot bind ribosomes. Thus, these results provide a new mechanism underlying FMRP activity that contributes to altered development in FXS. Moreover, these data confirm the role of ribosomal RACK1 as a ribosomal scaffold for RNA binding proteins.

© 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.

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.

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.

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.

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.

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 (

Background Incidentally diagnosed terminal ileitis [IDTI] has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis. Methods We performed a systematic review using three biomedical databases [Medline, Embase, and Web of Science] and relevant scientific meeting abstracts. We identified observational studies that reported the prevalence of IDTI in adults undergoing screening or polyp surveillance colonoscopy and/or the long-term outcomes of such lesions. A random-effects meta-analysis was conducted to determine the pooled prevalence rate of IDTI. The progression of IDTI to overt Crohn’s disease [CD] was also described. Results Of 2388 eligible studies, 1784 were screened after excluding duplicates, 84 were reviewed in full text, and 14 studies were eligible for inclusion. Seven studies reported the prevalence of IDTI in 44 398 persons undergoing non-diagnostic colonoscopy, six studies reported follow-up data, and one study reported both types of data. The pooled prevalence rate of IDTI was 1.6% (95% confidence interval [CI] 0.1–21.8%) with significant heterogeneity [I2 = 99.7]. Among patients who had undergone non-diagnostic colonoscopy and had follow-up data [range 13–84 months reported in five studies], progression to overt CD was rare. Conclusions IDTI is not uncommon on non-diagnostic colonoscopies. Based on limited data, the rate of its progression to overt CD seems low, and watchful waiting is likely a reasonable strategy. Further long-term follow-up studies are needed to inform the natural history of incidental terminal ileitis, factors that predict progression to CD, and therapeutic implications.

Coronavirus disease 2019 (COVID-19) can cause gastrointestinal (GI) symptoms. A prior meta-analysis suggested that up to 17.6% of COVID-19 patients have GI symptoms. Data are conflicting on the association of GI symptoms with COVID-19 outcomes, with some reports suggesting worse prognosis among those with GI symptoms while others finding improved outcomes. There are limited data on COVID-19 and GI symptoms among inflammatory bowel disease (IBD) patients. A single-center study of 80 IBD patients with COVID-19 observed that they were more likely to present with abdominal pain and diarrhea than non-IBD controls. In addition, a prior systematic review on just over 400 patients found nearly one-quarter of IBD patients with COVID-19 had diarrhea.6 Using a large, international database, we aimed to describe new onset GI symptoms and their association with clinical outcomes in patients with IBD who develop COVID-19.

Background Comorbidities increase the risk of coronavirus disease 2019 (COVID-19) hospitalization and mortality. As many comorbidities are common in patients with inflammatory bowel diseases (IBD), we sought to investigate the effects of comorbidities in these patients on infection severity. Aim To evaluate association between individual comorbidities and COVID-19 infection severity among patients with IBD. Methods Data were obtained from SECURE-IBD, an international registry created to evaluate COVID-19 outcomes in patients with IBD. We used multivariable regression to analyze associations between eleven non-IBD comorbidities and a composite primary outcome of COVID-19-related hospitalization or death. Comorbidities were first modeled individually, adjusting for potential confounders. Next, to determine the independent effect of comorbidities, we fit a model including all comorbidities as covariates. Results We analyzed 2,035 patients from 58 countries (mean age 42.7 years, 50.6% male). A total of 538 patients (26.4%) experienced severe COVID-19. All comorbidities but a history of stroke and obesity were associated with severe infection in our initial analysis, with adjusted odds ratios ranging from 1.9 to 3.7. In a model including all comorbidities significantly associated with the composite outcome in the initial analysis, as well as other confounders, most comorbidities remained significant, with the highest risk in chronic kidney disease and chronic obstructive pulmonary disease. Conclusion Many non-IBD comorbidities are associated with a two to threefold increased risk of COVID-19 hospitalization or death among patients with IBD. These data can be used to risk-stratify and guide treatment and lifestyle decisions during the ongoing pandemic.

The coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented loss of life and health on a global scale. COVID-19 outcomes are more severe among those with comorbid conditions, which raises concerns for patients with inflammatory bowel disease (IBD), especially given the increased infection risk with immunosuppression used for IBD therapy.

Polygenic and environmental factors are underlying causes of inflammatory bowel disease (IBD). We hypothesized that integration of the genetic loci controlling a metabolite's abundance, with known IBD genetic susceptibility loci, may help resolve metabolic drivers of IBD.We measured the levels of 1300 metabolites in the serum of 484 patients with ulcerative colitis (UC) and 464 patients with Crohn's disease (CD) and 365 controls. Differential metabolite abundance was determined for disease status, subtype, clinical and endoscopic disease activity, as well as IBD phenotype including disease behavior, location, and extent. To inform on the genetic basis underlying metabolic diversity, we integrated metabolite and genomic data. Genetic colocalization and Mendelian randomization analyses were performed using known IBD risk loci to explore whether any metabolite was causally associated with IBD.We found 173 genetically controlled metabolites (metabolite quantitative trait loci, 9 novel) within 63 non-overlapping loci (7 novel). Furthermore, several metabolites significantly associated with IBD disease status and activity as defined using clinical and endoscopic indexes. This constitutes a resource for biomarker discovery and IBD biology insights. Using this resource, we show that a novel metabolite quantitative trait locus for serum butyrate levels containing ACADS was not supported as causal for IBD; replicate the association of serum omega-6 containing lipids with the fatty acid desaturase 1/2 locus and identify these metabolites as causal for CD through Mendelian randomization; and validate a novel association of serum plasmalogen and TMEM229B, which was predicted as causal for CD.An exploratory analysis combining genetics and unbiased serum metabolome surveys can reveal novel biomarkers of disease activity and potential mediators of pathology in IBD.

Background & Aims The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. Methods Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. Results Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10–54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10–7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12–36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. Conclusions Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins.We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin.The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P.001 in validation cohort 1 and 0.624, P = .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P = .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P = .298 in validation cohort 2).We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.

Key Points Question Is receipt of tumor necrosis factor (TNF) inhibitor monotherapy at the time of COVID-19 diagnosis associated with adverse COVID-19 outcomes compared with other treatment regimens among patients with immune-mediated inflammatory diseases (IMIDs)? Findings In this cohort study of 6077 patients with IMIDs and COVID-19, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, or Janus kinase inhibitor monotherapy were each associated with significantly higher odds of hospitalization or death compared with TNF inhibitor monotherapy. Meaning This study’s findings support the continued use of TNF inhibitor monotherapy among individuals with IMIDs during the pandemic., Importance Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19–associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures The main outcome was COVID-19–associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P, This cohort study uses data from 3 international registries to examine the association between the receipt of tumor necrosis factor monotherapy and the risk of COVID-19–associated hospitalization or death among adult patients with immune-mediated inflammatory diseases.

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States.1 Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19.2 Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access.3 Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities.

The inflammatory bowel diseases [IBDs], inclusive of Crohn’s disease [CD] and ulcerative colitis [UC], are chronic, progressive immune-mediated diseases associated with high morbidity and substantial economic impact. The pathogenesis implicates a complex interaction between environmental determinants and genetic susceptibility. Of concern, the incidence and prevalence of IBD are increasing globally, with the highest relative increase observed in developing and recently developed countries. One high-risk yet underappreciated population is immigrants from countries of low to high IBD incidence, as evidenced by epidemiologic studies demonstrating higher risk of IBD among second- versus first-generation and younger versus older immigrants from low- to high-incidence countries [LTHICs]. The reasons underlying these emerging patterns among immigrants are incompletely understood and provide enormous opportunities to better define the pathophysiology of IBD and move toward disease prevention or at least earlier diagnosis. The rapidity of this epidemiologic shift in the demographic profile of IBD, which was traditionally a disease of Caucasians in industrialized countries, strongly implicates non-genetic factors and gene–environment interactions in the pathophysiology of IBD among immigrants from LTHICs. The primary objectives of this Viewpoint are to [1] provide a focused overview of IBD epidemiology among immigrants from countries at differential IBD risk; [2] emphasize the potential to advance our understanding of IBD pathogenesis via targeted research efforts to delineate risk and protective determinants in this cohort; and [3] highlight disparities and barriers in IBD care, as well as the economic implications of the rising, yet underappreciated, disease burden among immigrants from LTHICs.

ObjectiveThe benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DesignOur primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.ResultsA total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.ConclusionIn two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.

Background & Aims Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBDs). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. Methods We conducted a retrospective cohort study, collecting data from 5 medical centers, on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. Results Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse after a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18–2.71; HR for immunomodulators, 2.22; 95% CI, 1.38–3.55; HR for biologics, 1.95; 95% CI, 1.01–5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21–3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01–3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank, 0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. Conclusions In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

Background Immune-mediated inflammatory diseases (IMIDs) are systemic diseases of multifactorial etiology that share aberrant immune responses as the common final pathway. With rising globalization, their incidence is increasing in developing countries and among immigrants. Our primary objective was to systematically review the epidemiology of IMIDs in immigrants and conduct a meta-analysis to estimate the risk of IMIDs in immigrant populations according to their origin and destination countries. Methods We systematically searched five biomedical databases and reviewed population-based studies, from inception through August 2018, that reported incidence or prevalence data of inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriasis and psoriatic arthritis (PPA) among immigrants and the host population. Results The incidence and prevalence of IMIDs among immigrants differ from host populations, and evolve over subsequent generations. The risk of IBD among immigrants approximates that in hosts, especially among South Asians, with ulcerative colitis incidence changing prior to Crohn’s disease incidence. MS risk is highest in Iranian immigrants, T1D in African immigrants and SLE in African and Iraqi immigrants. Data on other IMIDs are sparse. Significant heterogeneity between the studies precluded meta-analysis. Conclusion Based on our systematic review, the epidemiology of IMIDs among immigrants varies according to native and host countries, immigrant generation, and IMID type. The rapid evolution suggests a role for non-genetic factors and gene-environment interactions. Future studies should focus on these pattern shifts, given implications of rising global burden of IMIDs and immigration.

Osteoporosis, a global health problem, is now frequently recognized to be secondary to alterations in the pituitary-bone axis. This review examines the current evidence for how dysregulation of the pituitary-bone axis leads to osteoporotic bone loss. Specifically, perimenopausal bone loss in the context of follicle-stimulating hormone action, and hyperthyroid bone loss in the context of thyroid-stimulating hormone action are explored. From the reviewed scientific findings, recommendations for early diagnosis and better clinical management of bone loss are made.

OBJECTIVES: Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients. METHODS: A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (

Background & Aims Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. Methods We performed a retrospective analysis of data from 333 patients with IBD treated at 8 academic medical centers who developed cancer and subsequently received treatment with anti–tumor necrosis factor (TNF), anti-TNF with an antimetabolite (thiopurines, methotrexate), antimetabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated by using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared by using the log-rank test. Results During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible because of the relatively small sample sizes. There was no difference in time to incident cancer ( P = .14) or type of incident cancer ( P = .61) among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF, 0.32; 95% confidence interval [CI], 0.09–1.09; HR for anti-TNF with an antimetabolite, 0.64; 95% CI, 0.26–1.59; HR for an antimetabolite, 1.08; 95% CI, 0.54–2.15) or time to subsequent cancer between study arms ( P = .22). Conclusion On the basis of a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an antimetabolite after cancer was not associated with an increased risk of incident cancer, compared with patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.

Osteoporosis is a leading cause of morbidity in patients with inflammatory bowel disease (IBD). Bone loss is an early systemic process and occurs even before clinical disease manifests. Bone disease is attributed to vitamin D deficiency, steroid use, and/or systemic inflammation. In this review, we discuss the molecular pathways of bone loss mediated by inflammatory cytokines and other mediators. Further research will hopefully clarify the mechanisms of inflammation-induced bone loss in IBD and guide effective treatment modalities.

In nonneuronopathic type 1 Gaucher disease (GD1), mutations in the glucocerebrosidase gene (GBA1) gene result in glucocerebrosidase deficiency and the accumulation of its substrate, glucocerebroside (GL-1), in the lysosomes of mononuclear phagocytes. This prevailing macrophage-centric view, however, does not explain emerging aspects of the disease, including malignancy, autoimmune disease, Parkinson disease, and osteoporosis. We conditionally deleted the GBA1 gene in hematopoietic and mesenchymal cell lineages using an Mx1 promoter. Although this mouse fully recapitulated human GD1, cytokine measurements, microarray analysis, and cellular immunophenotyping together revealed widespread dysfunction not only of macrophages, but also of thymic T cells, dendritic cells, and osteoblasts. The severe osteoporosis was caused by a defect in osteoblastic bone formation arising from an inhibitory effect of the accumulated lipids LysoGL-1 and GL-1 on protein kinase C. This study provides direct evidence for the involvement in GD1 of multiple cell lineages, suggesting that cells other than macrophages may be worthwhile therapeutic targets.

The use of antiretroviral therapy has significantly reduced the number of deaths due to HIV/AIDS. However, no current therapy can suppress the virus completely, and as the HIV-infected population continues to live longer new complications are emerging from the persistence of the virus and use of antiretroviral therapy. This review summarizes the clinical evidence linking HIV-associated osteoporosis to direct infection and antiretroviral therapy (ART) use. The purported molecular mechanisms involved in bone loss are also reviewed. Additionally, recommendations regarding the pharmacologic management of HIV/ART-related osteoporosis are given.