Tao Su

Background and Aims: Inflammatory Bowel Disease presents significant management challenges, particularly in pediatric and elderly populations with refractory conditions. Despite advances in biologic therapies, current treatments remain limited with inconsistent response rates. This study investigated Upadacitinib efficacy in Asian adolescent and elderly populations with refractory IBD. Methods: This single-center, retrospective cohort study examined 21 patients at the Sixth Affiliated Hospital of Sun Yat-sen University: 11 pediatric refractory CD patients (aged 9– 17) and 10 elderly refractory UC patients (aged 60+). Diagnoses were confirmed via comprehensive criteria including clinical symptoms, biomarkers, endoscopic findings, histological examination, and radiological results. Patients had refractory IBD, defined as failure of at least two biologic agents with distinct mechanisms or comorbid psychosocial complications impairing disease management. Results: Pediatric CD patients showed remarkable efficacy, with 72.7% achieving steroid-free clinical remission at week 12, maintained at 57.1% by week 24, and reaching 88.9% at final follow-up. Endoscopic remission improved from 50% at week 12 to 57.1% at final follow-up. Elderly UC patients showed modest outcomes, with 20% achieving clinical remission throughout the study. Laboratory parameters demonstrated significant improvements, particularly in C-reactive protein and albumin levels. The safety profile was generally favorable with minimal adverse events. Teenage CD patients experienced minor dermatological side effects, while UC patients showed no significant adverse events. One serious pneumonia case in the elderly group highlighted potential infection risks. Conclusion: This pioneering Asian study provides critical insights into UPA’s potential as alternative treatment for challenging IBD cases in adolescent and elderly populations, demonstrating different efficacy and safety profiles across age groups and contributing evidence for personalized medicine approaches in managing refractory IBD.

Background Endoscopic balloon dilation (EBD) is recognized as a minimally invasive and effective procedure for managing intestinal stenosis in patients with Crohn’s disease (CD). It offers an alternative to surgery and has been shown to improve the quality of life for these patients by reducing the need for more aggressive interventions. This study aimed to evaluate factors associated with endoscopic restenosis after EBD and construct a prognostic model. Methods We retrospectively collected and analyzed data on patients receiving EBD treatment at the Sixth Affiliated Hospital of Sun Yat-sen University from 2013 to 2024. Seven machine learning (ML) algorithms were used to construct prognostic models. Subsequently, we conducted comparative tests on the performance of the models to ensure accuracy and reliability. Results A total of 135 patients were included in the statistical analysis. 53% occurred endoscopic restenosis, with an average restenosis time of 183 days. COX and logistic regression analysis showed that 4 features including ever-use glucocorticoids, stenosis position, technical success, and albumin level were associated with restenosis risk. When comparing different ML models, CoxPH and LASSO models performed better on various evaluation metrics, including C-index which was greater than 0.7 in the train and test set. Based on SHapley Additive exPlanations (SHAP), stenosis position, balloon diameter, and albumin level were identified as the top 3 important features associated with prognosis. Conclusion The ML-based prognostic model has good predictive performance and can accurately assess the risk of endoscopic restenosis after EBD treatment.

Background and Aims: Inflammatory bowel disease (IBD) requires effective treatment options. Upadacitinib, a Janus kinase 1 (JAK1) inhibitor, has shown effectiveness in trials for Crohn’s disease (CD) and ulcerative colitis (UC). This study evaluates its real-world effectiveness and safety. Methods: We conducted a multicenter retrospective cohort study in tertiary care centers, involving patients treated with upadacitinib from January 2023 to September 2024. The study included adult patients aged 18 years or older, diagnosed with UC or CD, who received at least 8 weeks of upadacitinib therapy. Treatment outcomes were evaluated using established clinical, endoscopic, imaging, histological, and laboratory parameters. Results: A total of 236 IBD patients received upadacitinib treatment. In 80 UC patients at 8 weeks, 64.0% achieved steroid-free remission, 57.6% clinical remission, and 81.8% response. Endoscopic remission was 35.8% (p = 0.039), with 63.3% response and 35.8% mucosal healing. Histological remission reached 29.2% (p = 0.009). For 156 CD patients at 12 weeks, 76.8% achieved steroid-free remission (p < 0.001), 77.8% clinical remission (p < 0.001), and 81.0% response. Mean CDAI decreased from 214.9 to 117.5 (p < 0.001). Endoscopic remission was 19.4%, with 48.9% response and 4.9% mucosal healing. Radiological remission was 9.1% with 85.7% response. Intestinal ultrasound showed 5.7% remission and 56.7% response. Conclusions: Upadacitinib demonstrates significant real-world effectiveness and safety in IBD, particularly in biologic-resistant cases, as evidenced by high rates of steroid-free remission and clinical response. These outcomes are likely due to its targeted JAK1 inhibition, which effectively reduces inflammation and promotes mucosal healing. Future research should focus on long-term safety, comparative effectiveness with other biologics, and its application in diverse patient populations. These findings support the integration of upadacitinib into IBD management strategies.

Background: Ustekinumab (UST) is recommended as the first-line treatment for patients with moderate to severe Crohn’s disease (CD). However, the efficacy of certain patients may be suboptimal and necessitate intensive treatment or modification of the treatment regimen. We sought to establish a nomogram model to predict the short-term effectiveness of UST in moderate to severe CD patients. Methods: We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University from May 2020 to July 2023. The patient data, including demographic and clinical characteristics as well as treatment details, were systematically collected. The achievement of clinical remission (defined as Crohn’s Disease Activity Index, CDAI < 150, without corticosteroid usage) after induction therapy was the endpoint observed during follow-up. Potential predictors were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Subsequently, a multivariate logistic regression analysis was conducted to construct a nomogram model. The predictive accuracy and discriminative power of the model were assessed by Receiver Operating Characteristics (ROC) curves and calibration curves. Decision curve analysis (DCA) was employed to assess the clinical application value of the model. Results: 162 patients were included in the derivation cohort. The predictor’s selection was according to the minimum criteria. Prognostic factors, including duration, body mass index (BMI), smoking, extraintestinal manifestations (EIMs), perianal lesions (P), history of Vedolizumab therapy, and albumin levels (ALB), were identified and included in the nomogram. The model showed good discrimination and calibration on internal validation based on the bootstrap method (C-index: 0.843, 95% confidence interval: 0.768– 0.903). Moreover, DCA demonstrated that the nomogram was clinically beneficial. Conclusion: We constructed a practical tool to assist clinicians in identifying moderate to severe CD patients who are expected to have a good clinical response to UST, promoting personalized treatment and the development of precision medicine.

Background Epidemiological studies have indicated a frequent co-occurrence of Graves' disease (GD) with other immune-mediated diseases (IMDs). However, the causal relationship between them remains uncertain. Objective This study aimed to establish a causal relationship between GD and IMDs, as well as investigate the genetic foundation of comorbidities. Methods We employed Mendelian randomization (MR) to infer a causal relationship between GD and eight IMDs in the East Asian population, namely, systemic lupus erythematosus (SLE), ulcerative colitis (UC), rheumatoid arthritis (RA), atopic dermatitis (AD), Crohn's disease (CD), type 1 diabetes mellitus (T1DM), amyotrophic lateral sclerosis (ALS), and asthma. The causal association was examined using several MR methods. A sensitivity analysis was performed to identify potential heterogeneity and pleiotropy. Finally, we performed colocalization analyses to explore the possible genetic foundation. Results Bidirectional MR analysis indicated that GD increased the risk of SLE (odds ratio [OR]: 1.31, 95% Confidence Interval [CI]: 1.15 to 1.49, P < 0.001) and CD (OR: 1.32, 95%CI: 1.14 to 1.52, P < 0.001), and maybe a risk factor for RA, but a protective factor for AD and asthma. And we found that RA was linked to a higher risk of GD (OR: 1.26, 95%CI: 1.09 to 1.46, P = 0.002). UC and AD may be protective factors for GD, while CD was the opposite. Colocalization analyses suggested that shared causal variants between GD and other IMDs may exist. Conclusion This study has confirmed that GD was associated with IMDs. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

Background: Type 1 diabetes mellitus (T1DM) and inflammatory bowel disease (IBD) are common autoimmune diseases. Previous studies reported an association between these two diseases. However, due to the limitations of observational research, it cannot provide sufficient evidence to support the existence of causality or reverse causality. Objective: This study aimed to evaluate the existence of the causal relationship between T1DM and IBD. Methods: A two-sample bidirectional Mendelian randomization (MR) was employed to investigate a possibility of the causal relationship between T1DM and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Independent genetic variants of T1DM and IBD were retrieved from the IEU OpenGWAS project，and the individuals were of European ancestry. After filtering the single nucleotide polymorphisms (SNPs), several MR methods, including MR–Egger regression, weighted median, inverse variance-weighted (IVW), and weighted mode with IVW as the primary analysis method, were used to test the causal association between the two diseases. Furthermore, a sensitivity analysis was conducted to detect the heterogeneity and pleiotropy of the instrumental variables. Results: Bidirectional MR analysis indicated a negative correlation between T1DM and IBD (IVW OR: 0.95, 95% Confidence Interval [CI]: 0.94 to 0.97, P = 1.19E-12). However, a separate analysis of CD and UC showed that this negative association appeared to exist only for T1DM and CD (IVW OR: 0.95, 95% CI: 0.91 to 0.99, P = 0.0063) and not for UC (IVW OR: 1.02, 95% CI: 0.98 to 1.05, P = 0.3315). In contrast, we found no difference in the prevalence of T1DM among patients with IBD, CD, and UC compared to the general population. Conclusions: This study using MR has confirmed that individuals diagnosed with T1DM exhibit a decreased susceptibility to IBD in comparison to the general population，indicating that new therapeutic targets for IBD based on the pathogenesis of T1DM should be explored.

There is insufficient evidence to confirm the efficacy of ustekinumab (UST) in promoting fistula closure in perianal fistulizing Crohn’s disease (CD) patients. We aimed to evaluate the efficacy of UST in a real-world setting. The data were retrospectively analyzed. Intestinal clinical and endoscopic changes were evaluated. Fistula radiological outcomes were determined using the Van Assche score. A total of 108 patients were included, 43.5% of whom had complex perianal fistulas. Intestinal clinical and endoscopic remission was achieved in 65.7% and 31.5% of patients, respectively. The fistula clinical remission and response rates were 40.7% and 63.0%, respectively, with a significant reduction in Perianal Crohn’s disease Activity Index [5.0(3.0, 8.0) vs. 7.5(5.0, 10.0), p < 0.001] and Crohn’s Anal Fistula Quality of Life [23.5(9.3, 38.8) vs. 49.0(32.3, 60.0), p < 0.001]. Radiological healing, partial response, no change, and deterioration were observed in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively. The cut-off UST trough concentration for predicting fistula clinical remission was 2.11 μg/mL with an area under the curve of 0.795, a sensitivity of 93.3%, and a specificity of 67.6%. UST is efficacious in promoting radiological fistula closure in patients with perianal fistulizing CD. A UST trough concentration over 2.11 μg/mL was correlated with a higher likelihood of perianal fistula clinical remission.