Citations

Abstract Despite advances in endoscopic techniques, many colorectal surgeries in the United States are still performed for non-malignant colorectal polyps (NMCRPs). This study evaluated trends, demographic variations, and outcomes of surgeries for NMCRPs among all colorectal surgeries over the past decade. Using the TriNetX nationwide database, we identified adults (≥ 18 years of age) who underwent colectomy or proctectomy for NMCRPs or colorectal cancer between 2013 and 2023. We evaluated the proportion of surgeries performed for NMCRPs, stratified by demographic factors, and compared postoperative adverse events (AEs) between NMCRP and colorectal cancer surgeries. Among 136,721 surgeries, 52,480 (38.4%) were for NMCRPs. The proportion of NMCRP surgeries decreased from 59% in 2013 to 33% in 2023, with the most significant decline between 2013 and 2016. Black individuals showed the highest decrease. Compared with colorectal cancer surgeries, NMCRP surgeries were associated with significantly lower risks of wound, infectious, urinary, pulmonary, gastrointestinal, and cardiac AEs. Although the proportion of NMCRP surgeries has declined, ongoing efforts in education and training are needed to further reduce unnecessary surgeries and improve patient outcomes.

ABSTRACT Background Ehlers–Danlos syndrome (EDS) comprises inherited connective tissue disorders characterised by joint hypermobility, skin hyperextensibility and tissue fragility. It links to systemic comorbidities, including gastrointestinal (GI) disorders, but hitherto large‐scale data remain limited. We aimed to evaluate the prevalence of GI, systemic and psychological comorbidities in EDS patients versus propensity score‐matched controls, using a comprehensive research network database. Design This was a retrospective, propensity‐matched analysis (2005–2023) utilising the TriNetX network. We identified EDS patients (excluding Marfan's syndrome). Propensity score matching (1:1) generated balanced cohorts for age, sex and baseline characteristics. Comorbidities were analysed via prevalence rates and odds ratios (ORs) with 95% confidence intervals (CIs). Results Matched cohorts included 59,128 pairs. Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR 1.5, 95% CI 1.4–1.5, p < 0.001), followed by constipation (12.4%, OR 1.8, 95% CI 1.7–1.9, p < 0.001), irritable bowel syndrome (7.3%, OR 2.6, 95% CI 2.5–2.8, p < 0.001) and gastroparesis (4.7%, OR 8.2, 95% CI 7.3–9.2, p < 0.001). Psychiatric conditions showed heightened prevalence of anxiety (26.1%, OR 1.8, 95% CI 1.7–1.8, p < 0.001) and depression (18.7%, OR 1.3, 95% CI 1.2–1.3, p < 0.001). Systemic comorbidities included postural orthostatic tachycardia syndrome (13.2%, OR 899.7, 95% CI 483.8–1673.0, p < 0.001), chronic pain (7.9%, OR 7.0, 95% CI 6.4–7.6, p < 0.001), migraines (19.7%, OR 2.5, 95% CI 2.4–2.6, p < 0.001) and fibromyalgia (9.5%, OR 1.7, 95% CI 1.6–1.8, p < 0.001). Conclusion EDS patients exhibit heightened risk for GI, systemic and psychological comorbidities, highlighting the importance of multidisciplinary approaches for effective management.

Abstract Background Patients with moderate-to-severe inflammatory bowel disease (IBD) often require immunosuppressive therapy to achieve and maintain remission; however, the impact of these medications on influenza risk and the severity of influenza-related complications remains inadequately characterized. Methods Using the TriNetX U.S. Analytics Network, adults (≥ 18 years) with Crohn’s disease or ulcerative colitis during the 2022–2023 influenza season were identified. Patients were stratified by disease activity into two cohorts: (1) moderate-to-severe/active IBD, defined by elevated inflammatory markers, initiation of corticosteroids or a new biologic or small-molecule agent, or documented IBD-related symptoms or complications within the prior six months; and (2) mild/inactive IBD, defined by the absence of these features and no recent immunosuppressive therapy. Propensity score matching (1:1) was used to balance baseline characteristics, and Cox proportional hazards models were applied to estimate hazard ratios for influenza-related outcomes. Results After propensity score matching, each group had 22,784 patients. The incidence of influenza diagnosis was significantly higher in the moderate-to-severe/active IBD group (HR 1.41; 95% CI, 1.30–1.52). Hospitalization rates were also increased (HR 2.05; 95% CI, 1.89–2.23), as were influenza-related complications (HR 1.36; 95% CI, 1.23–1.51). ICU admissions (HR 1.51; 95% CI, 1.33–1.72) and mechanical ventilation (HR 1.68; 95% CI, 1.32–2.13) were both more frequent in the moderate-to-severe/active IBD group. Use of antiviral medications was higher among those in this cohort (HR 1.60; 95% CI, 1.22–2.10), and overall mortality was modestly increased (HR 1.17; 95% CI, 1.02–1.35). Subgroup analysis revealed the highest risk among patients on corticosteroids, followed by JAK inhibitors and anti–IL-23 agents. Conclusion Patients with moderate-to-severe/active IBD had more severe influenza-related outcomes compared with mild/inactive controls. Improving vaccine uptake and prompt evaluation of upper respiratory symptoms during influenza seasons are key to reducing influenza-related risks in immunosuppressed patients with IBD.

Lay Summary In this study we evaluated the effectiveness of vedolizumab (anti-integrin) vs ustekinumab/risankizumab (anti-interleukin) therapy for isolated small-bowel Crohn’s disease using a real-world, multicenter national database. We found that anti-interleukin therapy was more effective for inducing steroid-free remission and reducing hospitalizations.

ABSTRACT Introduction Chronic pouchitis is a major therapeutic challenge in patients with ulcerative colitis following ileal pouch‐anal anastomosis. Methods We conducted a real‐world, propensity‐matched cohort study of 856 patients from a healthcare database to compare ustekinumab and vedolizumab. Results Ustekinumab was associated with significantly lower relapse rates (aHR = 0.69; p < 0.001), longer time to relapse, reduced hospitalisation and decreased need for steroids or antibiotics. No differences were observed in surgery rates or therapy switching. Conclusion Our findings suggest that ustekinumab may offer advantages over vedolizumab in the management of chronic pouchitis.

ABSTRACTBackground and ObjectiveSeladelpar is an oral, once‐daily medication that improves cholestasis through its selective peroxisome proliferator‐activated receptor (PPAR‐δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.MethodsA systematic review and meta‐analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).ResultsThree RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: −1.47 with 95% CI [−2.73, −0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).ConclusionSeladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC.Trial Registration: PROSPERO: CRD42024521208

ABSTRACT Introduction Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. Methods We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC‐IBD cohort) and PSC without IBD (PSC non‐IBD cohort), and were matched with patients without a history of PSC or IBD (non‐PSC/non‐IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan–Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time‐to‐event rates at daily time intervals. Results PSC patients without IBD were at increased risk of CRC compared to the non‐PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6–6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78–11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2–12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3–15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. Discussion Our findings provide real‐world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.

Abstract Patients with Crohn’s disease (CD) who undergo terminal ileum (TI) resection experience altered bile acid absorption, which may influence colorectal cancer (CRC) risk. We conducted a propensity-matched cohort study using TriNetX to compare CRC risk in patients with CD who underwent TI resection versus those who did not. Terminal ileum resection was associated with an increased risk of CRC (aHR = 2.58, 95% CI, 1.72–3.86). Patients with TI resection also had higher odds of colorectal polyps. These findings suggest the need for heightened CRC surveillance in patients with CD undergoing TI resection.

ABSTRACTIL‐17 inhibitors effectively treat psoriasis and psoriatic arthritis but may increase the risk of inflammatory bowel disease (IBD). We assessed their association with IBD compared to apremilast. Utilising the TriNetX database, we analysed patients with psoriasis or ankylosing spondylitis initiating IL‐17 inhibitors or apremilast. We used propensity score matching and Cox models to estimate IBD risk. Among 13,216 matched patients per group, 142 developed IBD with IL‐17 inhibitors versus 60 with apremilast (aHR = 2.50, 95% CI: 1.85–3.39). IL‐17 inhibitors increase IBD risk, necessitating careful patient selection and monitoring.