UNASSIGNED: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD).
UNASSIGNED: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson\'s Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence.
UNASSIGNED: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%-70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)].
UNASSIGNED: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.

UNASSIGNED: Selected patient groups with ulcerative colitis and Crohn\'s disease are at increased risk of colorectal cancer. Surveillance guidelines rarely cover patients after colectomy. We performed a nationwide population-based cohort study to estimate the risk of developing rectal cancer in patients with inflammatory bowel disease after subtotal colectomy.
UNASSIGNED: Through the Danish Civil Registration System, a source population of all individuals living in Denmark between 1978 and 2018 was retrieved. The risk of rectal cancer in patients with diverted rectum was assessed using Cox regression analyses with comparison to both the individuals with inflammatory bowel diseases without subtotal colectomy and the background population.
UNASSIGNED: Rectal cancer occurred in 42 of 4931 patients (0.9%) after subtotal colectomy and diverted rectum, compared to 209 of 49,251 (0.4%) in the matched inflammatory bowel diseases cohort without colectomy and 941 of 246,550 (0.4%) in the background population. The hazard ratio (HR) for rectal cancer in patients with inflammatory bowel disease and diverted rectum vs patients without colectomy was 0.76 (95% CI, 0.28, 2.07) before 10 years and 7.56 (95% CI, 5.21, 10.86) 10 years after colectomy. The HR for patients with diverted rectum compared to the background population was 0.84 (95% CI, 0.31, 2.24) and 10.01 (95% CI, 7.20, 13.94) respectively.
UNASSIGNED: In our nationwide population-based Danish cohort study, we found the risk of rectal cancer in the diverted rectum to be markedly increased 10 years postcolectomy. This calls for better long-term surveillance of colectomized patients with inflammatory bowel diseases.

BACKGROUND: To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment.
METHODS: Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used.
RESULTS: Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo.
CONCLUSIONS: Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.
Patients were willing to accept slightly higher risk treatment profiles over lower risk treatment profiles for an increased chance of achieving and maintaining remission. A patient-centric benefit-risk assessment suggested 200 mg of filgotinib had an acceptable benefit-risk profile.

BACKGROUND: The incidence and prevalence of inflammatory bowel diseases (IBD) are increasing around the world, especially in Western countries. The objective of this study was to evaluate the health habits of healthy controls and individuals with IBDs to identify possible risk factors for IBD development.
METHODS: A case-control study was conducted among Spanish participants over 18 years of age. A self-administered questionnaire was completed by subjects to collect information on several sociodemographic variables and habits, such as the consumption of tobacco, alcohol, antibiotics, nonsteroidal anti-inflammatory agents and macronutrients; anxiety and depression; and quality of life.
RESULTS: The main risk factors identified were age; living in an urban environment; anxiety; and excessive consumption of proteins, carbohydrates and fats. In addition, the consumption of fibre had a preventive effect against IBD development.
CONCLUSIONS: Age, anxiety and living in urban areas pose a risk of suffering from IBD, as does the excessive consumption of certain macronutrients. However, the consumption of fibre has a protective effect on the development of some IBD types.

Objective: This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC). Materials and Methods: We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and vice versa. The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses. Results: The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009-1.087; p = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn\'s Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015-1.073; p = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer (p > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022-1.211; p = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) (p > 0.05). Genetic predictions indicate a positive effect of Crohn\'s Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002-1.040; p = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032-1.168; p = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008-1.319; p = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations (p > 0.05). Conclusion: This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.

CONCLUSIONS: IBD patients have a 4.04-fold elevated likelihood of having CRS compared to non-IBD patients. CRS patients have a 4.23-fold elevated likelihood of having IBD compared to non-CRS patients. The risk of CRS development after IBD is five times higher than IBD development after CRS.

BACKGROUND: The impact of type 1 diabetes (T1D) on inflammatory bowel disease (IBD) remains unclear.
OBJECTIVE: To analyze the causal relationship between T1D and IBD using Mendelian ran-domization (MR).
METHODS: Single nucleotide polymorphisms were sourced from FinnGen for T1D, IBD, ulcerative colitis (UC) and Crohn\'s disease (CD). Inverse variance-weighted, MR-Egger, and weighted median tests were used to assess exposure-outcome causality. The MR-Egger intercept was used to assess horizontal pleiotropy. Co-chran\'s Q and leave-one-out method were used to analyze heterogeneity and sensitivity, respectively.
RESULTS: Our MR analysis indicated that T1D was associated with a reduced risk of IBD [odds ratio (OR): 0.959; 95% confidence interval (CI): 0.938-0.980; P < 0.001] and UC (OR: 0.960; 95%CI: 0.929-0.992; P = 0.015), with no significant association observed in terms of CD risk (OR: 0.966; 95%CI: 0.913-1.022; P = 0.227). The MR-Egger intercept showed no horizontal pleiotropy (P > 0.05). Cochran\'s Q and leave-one-out sensitivity analyses showed that the results were not heterogeneous (P > 0.05) and were robust.
CONCLUSIONS: This MR analysis suggests that T1D serves as a potential protective factor against IBD and UC but is independent of CD.

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Ferroptosis represents a novel mode of programmed cell death characterized by the intracellular accumulation of iron and lipid peroxidation, culminating in oxidative stress and subsequent cell demise. Mounting evidence demonstrates that ferroptosis contributes significantly to the onset and progression of diverse pathological conditions and diseases, including infections, neurodegenerative disorders, tissue ischemia-reperfusion injury, and immune dysregulation. Recent investigations have underscored the pivotal role of ferroptosis in the pathogenesis of rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, and asthma. This review provides a comprehensive overview of the current understanding of the regulatory mechanisms governing ferroptosis, particularly its interplay with iron, lipid, and amino acid metabolism. Furthermore, we explore the implications of ferroptosis in autoimmune diseases and deliberate on its potential as a promising therapeutic target for diverse autoimmune disorders.

UNASSIGNED: Genome-wide association studies (GWASs) have identified 38 loci associated with ulcerative colitis (UC) susceptibility, but the risk genes and their biological mechanisms remained to be comprehensively elucidated.
UNASSIGNED: Multi-marker analysis of genomic annotation (MAGMA) software was used to annotate genes on GWAS summary statistics of UC from FinnGen database. Genetic analysis was performed to identify risk genes. Cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signatures (UTMOST) was performed to compare GWAS summary statistics with gene expression matrix (from Genotype-Tissue Expression Project) for data integration. Subsequently, we used FUSION software to select key genes from the individual tissues. Additionally, conditional and joint analysis was conducted to improve our understanding on UC. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. The results of the four genetic analyses (MAGMA, UTMOST, FUSION and FOCUS) were combined to obtain a set of UC risk genes. Finally, Mendelian randomization (MR) analysis and Bayesian colocalization analysis were conducted to determine the causal relationship between the risk genes and UC. To test the robustness of our findings, the same approaches were taken to verify the GWAS data of UC on IEU.
UNASSIGNED: Multiple correction tests screened PIM3 as a risk gene for UC. The results of Bayesian colocalization analysis showed that the posterior probability of hypothesis 4 was 0.997 and 0.954 in the validation dataset. MR was conducted using the inverse variance weighting method and two single nucleotide polymorphisms (SNPs, rs28645887 and rs62231924) were included in the analysis (p < 0.001, 95%CI: 1.45-1.89). In the validation dataset, MR result was p < 0.001, 95%CI: 1.19-1.72, indicating a clear causal relationship between PIM3 and UC.
UNASSIGNED: Our study validated PIM3 as a key risk gene for UC and its expression level may be related to the risk of UC, providing a novel reference for further improving the current understanding on the genetic structure of UC.