Extraintestinal manifestations (EIMs) are a significant disease burden in inflammatory bowel disease (IBD). However, large-scale epidemiological data from the Chinese population remain scarce. This nationwide, multicenter, retrospective cross-sectional study included 2,252 adult IBD inpatients from 10 clinical centers. Data on demographics, clinical features, and EIMs were collected and analyzed using descriptive statistics and logistic regression. Of the 2252 patients, 384 (17.1

BACKGROUND:The aim of this study was to determine if Crohn's disease (CD) and ulcerative colitis (UC) manifest similarly in different parts of the world. METHODS:Investigators of cohort studies from around the world were contacted to provide the most recent data from their CD and UC cohorts. Each cohort provided summated and averaged data on pre-specified variables. The Montreal Classification was used for phenotype assessment. Age at diagnosis was stratified into less than 17 years, 17-39 years, and >39 years. Disease location for CD was stratified as ileum only, colon only, ileocolon, upper gastrointestinal and proximal small bowel disease, and perineal penetrating disease. Disease behavior for CD was stratified into inflammatory disease, stricturing disease, and penetrating disease. Location for UC was stratified into proctitis, left-sided colitis, and extensive including subtotal and pancolitis. Reports were classified geographically as Asia, Latin America, South Africa, and "Western" (ie, North America, Europe, and Oceania). These categories were collapsed to "Western" and "non-Western" for analyses. RESULTS:Data from 54 868 patients with IBD were included. For CD, data were available from nine Western cohorts, 12 Asian cohorts, three Latin American cohorts, and one African cohort. For UC, eight Western cohorts were compared with 11 Asian cohorts, three Latin cohorts, and one African cohort. The demographic and phenotypic distribution for CD and UC in comparisons between Western and non-Western countries were no different. Western cohorts had longer disease durations than non-Western cohorts. CONCLUSION:No significant differences were seen in any phenotypic data between the cohorts, suggesting that IBD is similar worldwide.

The increasing prevalence of inflammatory bowel disease (IBD) imposes a substantial economic burden, and its pathogenesis is associated with dietary fat intake. Short-chain fatty acids (SCFAs) regulate intestinal inflammation and immunity by inhibiting histone deacetylases (HDACs) or binding to G protein-coupled receptors (GPCRs). Specialized pro-resolving mediators (SPMs) derived from polyunsaturated fatty acids (PUFAs) contribute to inflammation resolution. Fatty acid oxidation (FAO) is a primary energy source for intestinal epithelial cells. Previous studies indicate that patients with IBD exhibit decreased levels of SCFAs and reduced intermediates of the tricarboxylic acid (TCA) cycle, suggesting impaired FAO. These alterations may exacerbate intestinal inflammation through energy deficiency in intestinal epithelial cells, barrier disruption, and dysregulated immune cell polarization. This review aims to broaden therapeutic options by identifying underlying targets and proposing potential strategies.

To characterize serum metabolic alterations across healthy controls, stable chronic obstructive pulmonary disease (SCOPD), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore candidate discriminatory metabolites for COPD-related comparisons. Serum samples from 19 patients with SCOPD, 20 patients with AECOPD, and 20 non-smoking healthy controls were analyzed by LC-MS/MS-based untargeted metabolomics. COPD groups showed reduced glycerophospholipid and alpha-linolenic acid metabolism compared with controls, whereas AECOPD showed enrichment of unsaturated fatty acid biosynthesis compared with SCOPD. PE(16:1(5Z)/16:1(5Z)) and 14,15-leukotriene C4 showed exploratory discriminatory potential in COPD-versus-control and AECOPD-versus-SCOPD comparisons, respectively. Because the study was small and lacked external validation, these metabolites should be interpreted as hypothesis-generating candidates requiring targeted validation.

Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory condition of the gastrointestinal tract that primarily includes Crohn's disease and ulcerative colitis. Beyond the typical gastrointestinal symptoms, IBD is frequently associated with various extraintestinal manifestations (EIMs) affecting organs such as joints, skin, eyes, and the hepatobiliary system. As the prevalence of IBD rises in China, the identification and management of EIMs have become increasingly important. However, there is currently variation among Chinese physicians in their attention to, comprehensive assessment of, and management of EIMs in IBD. Therefore, this consensus aims to provide guidance for the systematic evaluation and multidisciplinary management of IBD-associated EIMs.

Mirikizumab, a p19-directed anti-interleukin-23 antibody, demonstrated efficacy in patients with moderately-to-severely active ulcerative colitis in the global phase 3 LUCENT-1 induction (NCT03518086) and LUCENT-2 maintenance (NCT03524092) trials. The aim was to conduct a pre-specified Chinese subpopulation analysis of LUCENT-1 and LUCENT-2. In LUCENT-1, patients were randomized 3:1 to mirikizumab 300 mg or placebo intravenously every 4 weeks (Q4W) for 12 weeks. In LUCENT-2, patients with a clinical response to mirikizumab at week 12 of LUCENT-1 were re-randomized 2:1 to mirikizumab 200 mg or placebo via subcutaneous injection Q4W for 40 weeks. The primary endpoint in both trials was clinical remission at study end, defined as a Mayo stool frequency subscore of 0, or 1 with a ≥ 1-point decrease from baseline, rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1 (excluding friability). Among 183 Chinese patients included in the LUCENT-1 induction trial, clinical remission rates at week 12 were higher with mirikizumab 300 mg (n = 140) versus placebo (n = 43) (18.6

Introduction: The objective of this study was to investigate the predictive value of thromboelastography (TEG) combined with conventional coagulation test parameters for the clinical outcome of patients with trauma-induced coagulopathy (TIC) and establish and evaluate a clinical nomogram for predicting the prognosis of TIC patients. Methods: Clinical data of severe multiple trauma patients who underwent emergency treatment in the hospital from November 2018 to August 2021 were enrolled retrospectively. The prognosis was evaluated according to the length of hospital stay and the 30-day survival rate. Multivariable logistic regression model was used to evaluate the correlation between TEG parameters and clinical outcomes. A nomogram model was constructed and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value. Results: Univariate analysis indicated that there were significant differences in age, hypertension, temperature fluctuation (>3°C), transfusion, kinetics time (K), angle (α) value, maximal amplitude (MA), and international normalized ratio between the good and poor outcome group (P < 0.05). Multivariate logistic regression analysis showed that age, Glasgow Coma Scale scores, temperature fluctuation (>3°C), and MA parameters were independent risk factors for poor outcome, and we established the nomogram prediction model. According to ROC curve analysis, the area under the curve for MA parameter was 0.689 (95% confidence interval [CI]: 0.610–0.760), and the corresponding sensitivity and specificity were 44.12% and 91.87%, respectively. The area under the curve for temperature fluctuation (>3°C) was 0.697 (95% CI: 0.618–0.768), and the corresponding sensitivity and specificity were 60.00% and 79.67%, respectively. Conclusion: TEG parameters combined with relevant clinical indicators can be used to evaluate the prognosis of TIC patients with severe multiple trauma. The establishment of correlation nomogram model was guiding significance for clinical evaluation of long-term prognosis of trauma patients.

BACKGROUND:Etrasimod is an oral, once-daily sphingosine 1-phosphate (S1P) receptor modulator for the treatment of active ulcerative colitis. In the randomised, placebo-controlled, double-blind phase 3 ENLIGHT UC study, also known as the ES101002 study, we aimed to evaluate the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis in East Asia. METHODS:Using a central interactive web response system, in the 12-week induction period, adults (aged 18-75 years, inclusive) with moderately to severely active ulcerative colitis (modified Mayo score [MMS] 4-9 with an endoscopic subscore ≥2 and a rectal bleeding subscore ≥1) and an inadequate response, loss of response, or intolerance to at least one ulcerative colitis treatment were randomly assigned (2:1) to once-daily oral etrasimod 2 mg or placebo. Patients and study staff were masked to treatment assignment. Patients were enrolled from 52 hospitals across China, Taiwan, and Souh Korea. Randomisation was stratified by previous treatment status and baseline disease activity. Patients who had an MMS clinical response at induction period week 12 were re-randomly assigned (1:1) to once-daily oral etrasimod 2 mg or placebo for the 40-week maintenance period. Randomisation was stratified by induction period treatment, previous exposure to biologicals or JAK inhibitors, and concomitant use of oral corticosteroids at induction period baseline. The primary efficacy outcome was MMS clinical remission (stool frequency subscore=0 [or stool frequency subscore=1 with a ≥1 point decrease from induction period baseline], rectal bleeding subscore=0, and endoscopic subscore ≤1 [excluding friability]), assessed in the induction and maintenance periods separately (at induction period week 12 and maintenance period week 40). The primary efficacy analyses used the full analysis set (FAS), which included all patients who were randomly assigned and received at least one dose of study treatment for the induction period, and all re-randomly assigned patients who showed clinical response at induction period week 12 and received at least one dose of study treatment for the maintenance period. The safety analyses for each treatment period used the safety analysis set (SAF), which included all patients who received any amount of study drug in the corresponding treatment period. ENLIGHT UC is registered with ClinicalTrials.gov (NCT04176588) and the study is complete. FINDINGS:606 patients were screened between Sept 25, 2019, and April 27, 2023, and 340 were randomly assigned for the induction period and treated (FAS: 228 patients [88 female and 140 male] assigned to etrasimod and 112 patients [44 female and 68 male] assigned to placebo). 157 patients who showed clinical response in the induction period were re-randomly assigned and treated in the maintenance period (FAS: 77 patients [35 female and 42 male] assigned to etrasimod and 80 patients [32 female and 48 male] assigned to placebo). A significantly greater proportion of patients treated with etrasimod than those treated with placebo, showed clinical remission at induction week 12 (57 [25·0%] of 228 patients vs six [5·4%] of 112 patients; adjusted difference 20·4%; 95% CI 13·4%-27·4%; p<0·0001) and maintenance period week 40 (37 [48·1%] of 77 patients vs 10 [12·5%] of 80 patients; adjusted difference 35·9%; 95% CI 22·5%-49·2%; p<0·0001). In the induction period, the most frequently reported treatment-emergent adverse event (TEAE) was increased ALT (22 [10%] in the etrasimod group vs one [1%] in the placebo group). In the maintenance period, the most frequently reported TEAE was upper respiratory tract infection (14 [18%] in the etrasimod group vs 14 [17%] in the placebo group). Across the induction and maintenance periods, most TEAEs were mild to moderate in severity. Five (2%) of 228 patients treated with etrasimod and four (4%) of 112 patients treated with placebo discontinued study treatment due to TEAEs during the induction period, and one (1%) of 77 patients treated with etrasimod and one (1%) of 81 patients treated with placebo discontinued study treatment due to TEAEs during the maintenance period. No grade 4 or higher TEAE, malignancies, or deaths were reported. INTERPRETATION:Etrasimod was effective and well tolerated as an oral induction and maintenance treatment in patients with moderately to severely active ulcerative colitis in East Asia. FUNDING:Everest Medicines. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

BACKGROUND:Anorectal stricture is a severe and debilitating complication of Crohn's disease (CD). Currently, no specific patient-reported outcome measures (PROMs) exist to assess the severity of anorectal stricture or its impact on the quality of life (QoL) among patients with CD. A new PROM scale has been developed to measure CD anorectal stricture. METHODS:A 3-phase mixed-methods approach was implemented. Items were generated through a literature review and semi-structured interviews, followed by screening and refinement via pre-surveys and the Delphi method to create an initial scale. Cognitive interviews with patients were conducted to further optimize item content. Psychometric validation included structural validity assessments (comparisons with the hospital anxiety and depression scale [HADS] and the inflammatory bowel disease questionnaire [IBDQ]), as well as reliability and sensitivity evaluations through test-retest analysis. RESULTS:The study involved 171 patients with CD-associated anorectal stricture, 13 colorectal surgeons, 3 gastroenterologists, 1 general surgeon, and 1 nurse (all specializing in CD), along with 2 researchers experienced in PROM design, leading to the development of the Crohn's disease Anorectal Stricture Quality of Life Scale (CDAS-QoL). The scale demonstrated high internal consistency and reliability (Cronbach's α = 0.92; Guttman split-half = 0.84), good stability (Intraclass correlation coefficient = 0.87), and sensitivity (lower scores in patients with symptom improvement, P = .001; higher scores in those with symptom worsening, P = .03). CDAS-QoL scores were positively correlated with HADS scores (r = 0.66, P < .001) and negatively correlated with IBDQ scores (r = -0.67, P < .001). CONCLUSIONS:The CDAS-QoL scale is a validated PROM tool applicable to clinical decision-making and trials. It provides an effective instrument to quantify the severity of anorectal stricture in CD and assess its impact on patients' QoL.

Background: To standardize the treatment of inflammatory bowel disease (IBD) by establishing clear treatment targets and optimizing management strategies, the International Organization for the Study of IBD has proposed a treat-to-target (T2T) approach, which is now a popular management paradigm for IBD. However, this paradigm, which was derived primarily from Western countries with a high prevalence of IBD, has not been adopted universally. There is limited information on how T2T strategies are implemented around the world, and particularly in countries where IBD is a more recent phenomenon and has lower prevalence. Objectives: The aim of this study was to take advantage of the existence of the BRICS IBD Consortium (Brazil, Russia, India, China, and South Africa), a newly formed multinational organization, to get a realistic appraisal of gastroenterologists’ attitudes concerning the IBD treatment strategies. Design: A 59-question online questionnaire was distributed to 227 gastroenterologists from the BRICS countries between February and April 2024. Methods: Data on gastroenterologists’ characteristics, treatment strategies, and adoption of the STRIDE (Selecting Therapeutic Targets in Inflammatory Bowel Disease)-II consensus were collected, focusing primarily on viewpoints and challenges toward IBD T2T strategies. Results: More than 70% of respondents considered clinical and endoscopic remission, improved quality of life, absence of disability, and restoration of normal growth in children as the most important goals for IBD treatment. Concerns and challenges raised toward the International Organization for the Study of IBD (IOIBD) T2T strategy were the lack of a validated definition of mucosal healing (66.1%), guidelines conflicted with clinical experience (40.1%), psychological comorbidities (89.4%), loss of response to medical therapy (74.9%), complications associated with penetrating Crohn’s disease (CD; 74%), fistulising perianal CD (67.4%), and high out-of-pocket costs of therapeutic drug monitoring (69.6%). A step-up strategy was preferred (89%) in mild-to-moderate ulcerative colitis, whereas a top-down strategy was selected by the majority (72.2%) of respondents for CD management. Overall, the BRICS survey indicated that most of the participants had relatively high confidence in the IOIBD T2T recommendations. Conclusion: Although various concerns were identified, the BRICS survey showed that T2T strategies for IBD have been generally well received but not universally adopted by most gastroenterologists in countries with the more recent emergence of IBD.

BACKGROUND/AIMS:The development of antinuclear antibodies (ANAs) during infliximab treatment has been observed in previous clinical trials. To evaluate the clinical significance of ANA seroconversion and its potential association with the formation of antibodies against infliximab. METHODS:This retrospective study included 130 Crohn's disease patients undergoing infliximab therapy. ANA titers were measured at baseline and after 6 months of treatment. Inverse probability of treatment weighting was applied to control for confounding variables. RESULTS:Among the 111 patients with negative baseline ANA, 36 (32.4%) developed ANA positivity after 6 months of infliximab treatment. After adjustment with inverse probability of treatment weighting, a significantly higher proportion of patients in the ANA non-seroconversion group achieved endoscopic remission at 6 months compared to those with ANA seroconversion (64.5% vs. 35.5%: adjusted odds ratio [aOR], 3.61; 95% confidence interval [CI], 1.30-10.02; P= 0.014). At 18 months, patients in the non-seroconversion group also exhibited higher rates of both endoscopic response (57.5% vs. 42.3%: aOR, 3.38; 95% CI, 1.15-9.96; P= 0.027) and endoscopic remission (60.0% vs. 40.1%: aOR, 2.91; 95% CI, 1.06-8.01; P= 0.039) compared to the seroconversion group. Additionally, patients who developed ANA seroconversion had a higher rate of detectable antibodies against infliximab at both 6 and 18 months. A multivariable analysis identified female sex, older age at diagnosis, and lower serum albumin levels as independent predictors of ANA seroconversion at 6 months. CONCLUSIONS:ANA non-seroconversion at 6 months was associated with higher rates of endoscopic remission and a lower likelihood of developing antibodies against infliximab.

OBJECTIVES:Approximately 30% of patients with Crohn's disease (CD) experience primary loss of response (PLR) to ustekinumab. However, studies integrating imaging parameters to predict PLR remain limited. This study aimed to quantify endoluminal and intestinal wall parameters using computed tomography enterography (CTE) and assess their predictive value for PLR to ustekinumab. MATERIALS AND METHODS:This multicenter study analyzed 466 intestinal segments from 161 patients with CD between March 2020 and May 2024. A national survey identified 10 CTE parameters for evaluating disease activity and predicting PLR. Logistic regression models were used to assess predictive performance in a validation cohort. RESULTS:Ten CTE parameters related to lesion characterization-including length, luminal narrowing, and bowel wall thickness-were defined, with newly introduced metrics, including length, area, effective luminal diameter (EffLD), mean bowel wall thickness, and stenosis. A total of 352 baseline and 114 follow-up segments from 161 patients across six centers were analyzed to assess changes following ustekinumab treatment. Paired analysis across all patients showed significant improvements in eight parameters (p < 0.001); in contrast, unpaired comparisons between PLR and non-PLR groups revealed significant differences in six parameters (p < 0.001), with greater improvements in the non-PLR group. EffLD emerged as an independent predictor of ustekinumab response, with an AUC of 0.858 and an accuracy of 0.780 in the validation cohort. CONCLUSIONS:Novel endoluminal parameters, particularly EffLD, provide a detailed characterization of intestinal lesions in inflammatory bowel disease and exhibit strong predictive value for PLR in ustekinumab-treated patients with CD. CRITICAL RELEVANCE STATEMENT:This study first applied cardiovascular imaging software to quantify endoluminal CT enterography parameters, establishing effective luminal diameter as a novel, clinically applicable predictor of ustekinumab response in Crohn's disease. KEY POINTS:Cardiovascular imaging software can facilitate image analysis in Crohn's disease. Endoluminal CT enterography parameters predict primary loss of response in Crohn's disease. Effective luminal diameter independently predicts ustekinumab response.

Crohn’s disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.

Inflammatory bowel disease (IBD) is a gastrointestinal immune disease that requires clear diagnosis, timely treatment, and lifelong monitoring. The diagnosis and monitoring methods of IBD mainly include endoscopy, imaging examination, and laboratory examination, which are constantly developed to achieve early definite diagnosis and accurate monitoring. In recent years, with the development of nanotechnology, the diagnosis and monitoring methods of IBD have been remarkably enriched. Nanomaterials, characterized by their minuscule dimensions that can be tailored, along with their distinctive optical, magnetic, and biodistribution properties, have emerged as valuable contrast agents for imaging and targeted agents for endoscopy. Through both active and passive targeting mechanisms, nanoparticles accumulate at the site of inflammation, thereby enhancing IBD detection. This review comprehensively outlines the existing IBD detection techniques, expounds upon the utilization of nanoparticles in IBD detection and diagnosis, and offers insights into the future potential of in vitro diagnostics. STATEMENT OF SIGNIFICANCE: Due to their small size and unique physical and chemical properties, nanomaterials are widely used in the biological and medical fields. In the area of oncology and inflammatory disease, an increasing number of nanomaterials are being developed for diagnostics and drug delivery. Here, we focus on inflammatory bowel disease, an autoimmune inflammatory disease that requires early diagnosis and lifelong monitoring. Nanomaterials can be used as contrast agents to visualize areas of inflammation by actively or passively targeting them through the intestinal mucosal epithelium where gaps exist due to inflammation stimulation. In this article, we summarize the utilization of nanoparticles in inflammatory bowel disease detection and diagnosis, and offers insights into the future potential of in vitro diagnostics.

The prevalence of Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is increasing worldwide. The pathogenesis of CD is hypothesized to be related to environmental, genetic, immunological, and bacterial factors. Current studies have indicated that intestinal epithelial cells, including columnar, Paneth, M, tuft, and goblet cells dysfunctions, are strongly associated with these pathogenic factors. In particular, goblet cells dysfunctions have been shown to be related to CD pathogenesis by direct or indirect ways, according to the emerging studies. The mucus barrier was established with the help of mucins secreted by goblet cells. Not only do the mucins mediate the mucus barrier permeability and bacterium selection, but also, they are closely linked with the endothelial reticulum stress during the synthesis process. Goblet cells also play a vital role in immune response. It was indicated that goblet cells take part in the antigen presentation and cytokines secretion process. Disrupted goblet cells related immune process were widely discovered in CD patients. Meanwhile, dysbiosis of commensal and pathogenic microbiota can induce myriad immune responses through mucus and goblet cell-associated antigen passage. Microbiome dysbiosis lead to inflammatory reaction against pathogenic bacteria and abnormal tolerogenic response. All these three pathways, including the loss of mucus barrier function, abnormal immune reaction, and microbiome dysbiosis, may have independent or cooperative effect on the CD pathogenesis. However, many of the specific mechanisms underlying these pathways remain unclear. Based on the current understandings of goblet cell's role in CD pathogenesis, substances including butyrate, PPARγagonist, Farnesoid X receptor agonist, nuclear factor-Kappa B, nitrate, cytokines mediators, dietary and nutrient therapies were all found to have potential therapeutic effects on CD by regulating the goblet cells mediated pathways. Several monoclonal antibodies already in use for the treatment of CD in the clinical settings were also found to have some goblet cells related therapeutic targets. In this review, we introduce the disease-related functions of goblet cells, their relationship with CD, their possible mechanisms, and current CD treatments targeting goblet cells.

Background: Ulcerative colitis (UC) is a disease characterized by chronic relapsing-remitting inflammatory disorders and is associated with environmental changes. Aim: To explore the disease patterns of Chinese UC patients and to determine controllable related environmental factors. Methods: This multicentre cross-sectional study was performed using a questionnaire survey. Data on clinical characteristics and environmental factors were collected. Patients with a disease course >= 5 years were defined as the long course group, and those with a disease course < 5 years were defined as the short course group. Results: A total of 588 effective questionnaires were collected. The proportion of the chronic continuous pattern was the highest among patients with a long disease course (46.8%), and in patients with a short disease course, the proportion of the active to remission pattern was the highest (53.3%). In patients with a long disease course, a higher proportion of patients with adequate sleep was found in the active to remission pattern than in the chronic intermittent (72.1% vs. 43.3%, p = 0.008) and chronic continuous (72.1% vs. 52.4%, p = 0.016) patterns. In patients with a short disease course, the frequency of shellfish and shrimp was higher in the chronic continuous pattern group than in the active to remission pattern group (P = 0.001 and 0.017 respectively). Conclusions: For early diagnosis patients, dietary guidance should be actively carried out. With the prolongation of the disease course, attention should be given to the sleep quality of patients.