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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The efficacy of anti-TNF therapy in Crohn's disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes. Methods In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A > G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals. Results A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P  =   0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18–2.30, P  =   0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78–3.68, P  <   0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59–3.06, P  <   0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers. Conclusions HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients. [ABSTRACT FROM AUTHOR]

Objective.To evaluate the therapeutic efficacy and safety of perioperative electroacupuncture on postoperative abdominal pain in patients undergoing general anesthesia laparoscopic surgery. Methods.A total of 130 patients undergoing general anesthesia laparoscopic surgery were randomly divided into control group and experimental group. The control group received surgery under endotracheal intubation general anesthesia, while the experimental group received one session of electroacupuncture analgesia before and during anesthesia in addition to routine general anesthesia. The preoperative and postoperative pain Numerical rating scale (NRS), Pain Catastroph- izing Scale (PCS), Bruggrmann comfort scale (BCS), heart rate, and blood pressure were compared between the two groups. The occurrence of common adverse reactions after surgery, such as significant itching, rash, nausea, and vomiting, was observed. Results.No significant difference in activity NRS score was found between the two groups after surgery (P = 0.618). Compared with the control group, the experimental group had lower resting NRS score (2.05 ± 1.138),(1.62 ± 0.878), P = 0.017, lower PCS score (20.57 ± 8.538),(17.09 ± 8.291), P = 0.020, and higher BCS score after surgery (2.08 ± 1.035),(2.55 ± 1.046), P = 0.010, and decreased heart rate (76.17 ± 14.500),(70.85 ± 11.990), P = 0.024. There was no significant difference in systolic blood pressure between the two groups 12 and 24 hours after surgery (P > 0.05). A decrease in systolic blood pressure 24 hours after surgery was found in the experimental group when compared to that before surgery (125.6 ± 15.725), (123.60 ± 16.781), P = 0.040. Conclusion.Perioperative electroacupuncture stimulation can relieve postoperative abdominal pain, reduce heart rate and blood pressure, but does not increase the occurrence of adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Identifying patients with aggressive Crohn's disease (CD) threatened by a high risk of early onset surgery is challenging. Purpose: We aimed to establish and validate a radiomics nomogram to predict 1‐year surgical risk after the diagnosis of CD, thereby facilitating therapeutic strategies making. Methods: Patients with CD who had undergone baseline computed tomography enterography (CTE) examination at diagnosis were recruited and randomly divided into training and test cohorts at a ratio of 7:3. Enteric phase CTE images were obtained. Inflamed segments and mesenteric fat were semiautomatically segmented, followed by feature selection and signature building. A nomogram of radiomics was constructed and validated using a multivariate logistic regression algorithm. Results: A total of 268 eligible patients were retrospectively included, 69 of whom underwent surgery 1‐year after diagnosis. A total of 1218 features from inflamed segments and 1218 features from peripheral mesenteric fat were extracted, and reduced to 10 and 15 potential predictors, respectively, to construct two radiomic signatures. By incorporating the radiomics signatures and clinical factors, the radiomics‐clinical nomogram showed favorable calibration and discrimination in the training cohort, with an area under the curve (AUC) of 0.957, which was confirmed in the test set (AUC, 0.898). Decision curve analysis and net reclassification improvement index demonstrated the clinical usefulness of the nomogram. Conclusions: We successfully established and validated a CTE‐based radiomic nomogram with both inflamed segment and mesenteric fat simultaneously evaluated to predict 1‐year surgical risk in CD patients, which assisted in clinical decision‐making and individualized management. [ABSTRACT FROM AUTHOR]

Background: Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations., Objective: We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota., Methods: Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 × 10-6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia., Results: Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases., Conclusion: This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Peng, Gan, Wu, Ma, Zhi, Lu, Dai and Yao.)

Objectives: Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn's disease (CD)., Methods: This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn's disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded., Results: A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (-4.4, 65.9) vs. 69.0(10.7, 151.0), p  = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), p  = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety., Conclusion: Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways. Clinical Trial Registration: identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yao, Peng, Zhong, Su, Bihi, Zhao, Liu, Wang, Hu, Zhang and Zhi.)