Citations

Abstract Background Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. Results Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ± 12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn’s disease (CD) (mean age 56.3 ± 12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P < .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P < .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P < .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P < .01). Metformin did not affect risk for surgery in patients with UC. Conclusions Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.

INTRODUCTION: There are limited real-world data comparing the effectiveness of upadacitinib and tofacitinib in patients with ulcerative colitis (UC). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database, to compare the effectiveness of upadacitinib and tofacitinib in patients with UC. The primary aim was to assess the risk of a composite outcome of hospitalization requiring intravenous steroids and/or colectomy within 6 and 12 months. One-to-one propensity score matching was performed for demographics, comorbid conditions, mean hemoglobin, C-reactive protein, albumin, and calprotectin, and prior UC medications including recent oral or intravenous steroid use between the cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS: There were 526 patients in the upadacitinib cohort (mean age 40.4 ± 16.3, 44.8% female sex, 76.6% White race) and 1,149 patients in the tofacitinib cohort (mean age 42 ± 17.1, 41.9% female sex, 76% White race). After propensity score matching, there was no significant difference in the risk of the composite outcome of need for intravenous steroids and/or colectomy within 6 months (aOR 0.75, 95% CI 0.49–1.09). However, there was a lower risk of the composite outcome (aOR 0.63, 95% CI 0.44–0.89) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. There was no difference in the risk of intravenous steroid use (aOR 0.70, 95% CI 0.48–1.02) but lower risk of colectomy (aOR 0.46, 95% CI 0.27–0.79). In sensitivity analysis, there was also a lower risk of the composite outcome (aOR 0.64, 95% CI 0.44–0.94), including lower risk of intravenous steroid use (aOR 0.67, 95% CI 0.45–0.99) and colectomy (aOR 0.49, 95% CI 0.26–0.92) in the upadacitinib cohort compared with the tofacitinib cohort within 12 months. DISCUSSION: This study utilizing real-world data showed that upadacitinib was associated with improved disease-specific outcomes at 12 months compared with tofacitinib in patients with UC.

Summary Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) show anti‐inflammatory properties. Aim To evaluate their clinical impact on inflammatory bowel disease (IBD) outcomes. Methods Retrospective cohort study utilising the TriNetX database comparing IBD‐specific outcomes in patients with ulcerative colitis (UC) or Crohn's disease (CD) and type 2 diabetes mellitus (T2DM) on GLP‐1RA compared to oral hypoglycaemic agents. The primary outcome was hospitalisation requiring intravenous steroids and IBD‐related surgery within 3 years. We performed 1:1 propensity score matching (PSM) for demographics, co‐morbid conditions, BMI, laboratory values, HbA1c, and IBD medications including steroids. Results We identified 1130 patients in the UC GLP‐1RA cohort (mean age: 58.9 ± 11.6 years, 56.3% female, 70.2% White, 57.2% with obesity) and 1140 patients in the CD GLP‐1RA cohort (mean age: 56.7 ± 11.5, 61.9% female, 73.6% White, 56.2% with obesity). After PSM, there was no difference in the risk of intravenous steroid use (aHR: 1.21, 95% CI: 0.92–1.59) but a lower risk of colectomy (aHR: 0.37, 95% CI: 0.14–0.97) between the UC GLP‐1RA and control cohort. There was no difference in the risk of intravenous steroid use (aHR: 1.04, 95% CI: 0.80–1.34) but a lower risk of surgery (aHR: 0.55, 95% CI: 0.36–0.84) between the CD GLP‐1RA and CD control cohort. There was no difference in the risk of oral steroid use or advanced therapy initiation in the UC and CD GLP‐1RA than control cohorts. Conclusions We found an association between lower risk of IBD‐related surgery and GLP‐1RA use for T2DM in patients with UC or CD.

INTRODUCTION: There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1, 3, 5, and 10 years: the incidence of pouchitis, Crohn's-like disease of the pouch, use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records. METHODS: We performed a retrospective cohort study in TriNetX, a research network of electronic health records. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching, expressed as adjusted hazard ratios (aHRs). RESULTS: Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After propensity score matching, nicotine dependence (aHR 1.61, 95% confidence interval [CI] 1.19–2.18), antitumor necrosis factor therapy (aHR 1.33, 95% CI 1.13–1.56), and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06–1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of Crohn's-like disease of the pouch increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA. DISCUSSION: The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.

Lay Summary This retrospective study assessed the use of Janus kinase inhibitors in treating chronic pouchitis. While showing relative safety, Janus kinase inhibitors demonstrated effectiveness in <50% of cases, cautioning against their use as first-line agents. Larger randomized trials are recommended for further investigation.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.

Objectives The aim of this study was to study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016–2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk, and pancreatic enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching (PSM) of patients with EPI versus patients without an EPI diagnosis. Results The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years. After PSM, PDAC risk among patients with EPI was twice as high compared with patients without EPI (aHR, 1.97; 95% CI, 1.66–2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (adjusted odds ratio, 4.25; 95% CI, 2.99–6.04). Only 58% (n = 13, 390) of patients with EPI received PERT. No difference was observed in PDAC risk between patients with EPI on PERT and those not on PERT (aHR, 1.10; 95% CI, 0.95–1.26; P = 0.17). Conclusions Despite a low prevalence, patients with EPI may have a higher risk of PDAC, and majority with EPI were not on PERT. PERT did not impact incident PDAC risk after an EPI diagnosis.

Abstract Background Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown sustained and clinically significant weight loss in the general population. There are limited data on outcomes of its use in patients with inflammatory bowel disease (IBD). Methods A retrospective cohort study was conducted between June 4, 2021, and December 11, 2023, using TriNetX, a U.S. multi-institutional database in patients with obesity who had IBD compared with patients without IBD. The primary aim was to assess the mean total body weight (TBW) change between 6 and 15 months from initiation of semaglutide compared with baseline between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographics, comorbid conditions, smoking status, and mean body mass index. A 2-sample t test was performed to assess mean TBW change from baseline, with a P value <.05 considered to be statistically significant. We also compared the risk of IBD-specific outcomes with and without semaglutide use in patients with IBD. Results Out of 47 424 patients with IBD and obesity, 150 (0.3%) patients were prescribed semaglutide (mean age 47.4 ± 12.2 years; mean TBW 237 ± 54.8 pounds; mean body mass index 36.9 ± 6.5 kg/m2; 66% Crohn’s disease). There was no difference in mean TBW change after initiation of semaglutide in the IBD and non-IBD cohorts (−16 ± 13.4 pounds vs −18 ± 12.7 pounds; P = .24). There was no difference in mean TBW change between 6 and 12 months (−16 ± 13 pounds vs −15 ± 11.2 pounds; P = .24) and 12 and 15 months (−20 ± 13.2 pounds vs −21 ± 15.3 pounds; P = .49) between the 2 cohorts. There was no difference in the risk of oral or intravenous steroid use and any-cause hospitalization in the semaglutide group compared with the group without semaglutide use in patients with IBD. Conclusion Semaglutide use is effective in patients with IBD and obesity similar to patients without IBD, with >5% mean weight loss. There was no increased risk of IBD-specific adverse events with semaglutide use.