Alsakarneh, Saqr

ABSTRACT Background Immune checkpoint inhibitors (ICIs) enhance anti‐tumour immunity by modulating immune pathways but can also trigger immune‐related adverse events. We aimed to evaluate the risk of developing coeliac disease (CeD) among patients with malignancy treated with ICIs. Methods Using the TriNetX US Collaborative Network, we identified adults (≥ 18 years) diagnosed with malignancies for which ICIs are routinely used between January 2010 and December 2024 and stratified them by exposure to immune checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, tremelimumab, or avelumab). Patients with pre‐existing celiac disease (CeD) were excluded. Cohorts were propensity score matched for demographics and autoimmune comorbidities. The primary outcome was incident CeD occurring ≥ 90 days after the index event. Adjusted hazard ratios (aHRs) were calculated, with subgroup analyses by age and sex. Statistical significance was defined as p < 0.05. Results After propensity score matching, 158,208 patients were included in each cohort. CeD was diagnosed more frequently among patients exposed to ICIs than among matched controls (0.152% vs. 0.071%; aHR 3.95, 95% CI 3.11–5.03; p < 0.001), corresponding to a number needed to harm (NNH) of 1235. The increased risk persisted across sex and age subgroups, including females (aHR 3.43, 95% CI 2.55–4.62), males (aHR 5.36, 95% CI 3.53–8.12), with the risk being highest among patients older than 60 years (0.14% vs. 0.06%; aHR 4.24, 95% CI 3.17–5.67; p < 0.001). Conclusion In this large real‐world cohort, ICI exposure was associated with nearly a fourfold increase in the risk of being diagnosed with CeD compared with matched controls.

Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

ABSTRACT Background Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. Aim We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD–MPN coexistence. Methods Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non‐IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5‐year outcomes, including IBD‐related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. Results After matching, 3873 patients with UC–MPN and 3474 patients with CD–MPN were included. Compared with matched non‐IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL‐23 and JAK inhibitors were not. Conclusions IBD is associated with increased MPN risk, and IBD–MPNs coexistence is associated with worse IBD‐related complications and malignancy risk.

Background: Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, post-LT outcomes may differ depending on underlying disease etiology. Our study aimed to compare post-LT outcomes between alcoholic and non-alcoholic steatohepatitis (NASH)-related liver transplant recipients in the United States. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Adult liver transplant recipients (≥18 years) were categorized into two mutually exclusive cohorts: alcoholic liver disease and NASH-related liver disease. Propensity score matching (1:1) was performed to balance baseline characteristics. Clinical outcomes were assessed. Comparative analyses included risk ratios, risk differences, odds ratios, Kaplan–Meier survival analysis, and hazard ratios with log-rank testing. Results: Compared with NASH recipients, alcoholic LT recipients had a significantly higher risk of rejection (14.5% vs. 12.1%; RR 1.195, 95% CI 1.076–1.327; p = 0.001) and hepatic encephalopathy (14.3% vs. 8.3%; RR 1.720, 95% CI 1.526–1.938; p < 0.001). Acute kidney injury was also more frequent in the alcoholic cohort (47.3% vs. 43.6%; RR 1.084, 95% CI 1.036–1.133; p < 0.001). In contrast, sepsis (15.6% vs. 18.0%; RR 0.869, 95% CI 0.794–0.952; p = 0.003) and CKD (46.1% vs. 51.1%; RR 0.901, 95% CI 0.863–0.939; p < 0.001) occurred less frequently in alcoholic LT patients. No significant differences were observed for liver transplant failure or ascites. Kaplan–Meier analyses demonstrated significantly lower rejection-free survival (HR 1.241, p < 0.001), higher hepatic encephalopathy (HR 1.808, p < 0.001), increased AKI risk (HR 1.150, p < 0.001) and higher all-cause mortality in the alcoholic cohort (HR 1.106, p = 0.031). Conclusions: In this large real-world matched cohort study, alcoholic LT recipients demonstrated higher risks of complications and all-cause mortality compared with NASH LT recipients.

Colorectal cancer (CRC) is responsible for a high cancer burden and a high number of deaths all over the world, although effective screening can make it preventable to a significant extent. Stool-based tests, such as the fecal immunochemical test (FIT) and multitarget stool DNA (mt-sDNA) testing, are gaining considerable popularity as non-invasive procedures that can be a replacement for colonoscopies for people at an average risk for colon cancer. Despite evidence from several randomized controlled trials supporting the use of these tests for colorectal cancer screening, their external validity in a real-world setting is influenced by many factors such as adherence, timely follow-up post testing, the healthcare cost burden, accessibility and the capacity of the health system. In this article, we have performed an extensive narrative literature review of research published between 2020 and 2025 comparing FIT and the mt-sDNA test with reference to diagnostic accuracy, cost-effectiveness, adherence and outcomes of implementation. We discuss the issues of sensitivity and specificity, look at post-test requirements for colonoscopy and check if there is any discrimination in healthcare. These findings suggest that FIT and mt-sDNA tests should not be considered competing technologies but rather complementary screening methods, with their overall effectiveness contingent upon appropriate patient selection and widespread system-level implementation. It is crucial to combine strategic test selection with a robust follow-up infrastructure to ensure that the entire population benefits from the CRC prevention program.

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.