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Abstract In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to the blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown to independently impair aortic endothelial adhesion and increase rodent glioma model survival in combination with cytotoxic therapy. Yet additional research is required to understand ibrutinib’s effect on BTB function. In this study, we detail baseline BTK expression in glioma cells and its surrounding vasculature, then measure endothelial junctional expression/function changes with varied ibrutinib doses in vitro. Rat glioma cells and rodent glioma models were treated with ibrutinib alone (1–10 µM and 25 mg/kg) and in combination with doxil (10–100 µM and 3 mg/kg) to assess additive effects on viability, drug concentrations, tumor volume, endothelial junctional expression and survival. We found that ibrutinib, in a dose-dependent manner, decreased brain endothelial cell–cell adhesion over 24 h, without affecting endothelial cell viability (p

Background: Polysubstance use (PSU), the simultaneous use of 2 or more substances of abuse, is common in inflammatory bowel disease (IBD). Preliminary studies suggest it may be associated with poor outcomes. This prospective study evaluated the impact of PSU on disease activity and healthcare resource utilization in IBD., Methods: This study was conducted in a tertiary IBD center between October 29, 2015, and December 31, 2019. Participants were assessed over 2 time points (index and follow-up outpatient appointments) separated by a minimum of 6 months. Demographics, endoscopic disease activity, and surveys assessing symptoms, healthcare resource utilization and substance use (tobacco, alcohol, marijuana, cocaine, methamphetamine, heroin, opioid, or benzodiazepine) were abstracted. We identified PSU during the index appointment and computed descriptive statistics and contingency table analyses, and multivariate logistic regression models at follow up to evaluate outcomes., Results: 162 consecutively enrolled IBD patients were included. Seventy-five patients (46%) were polysubstance users at the index appointment. The most common cohorts were utilizing tobacco and alcohol (n=40) or tobacco and opioids (n=13). On bivariate and multivariate analyses, PSU during the index visit was positively associated with emergency department (ED) visits (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.24-5.07; P=0.01) and negatively associated with extraintestinal manifestations (OR 0.37, 95%CI 0.18-0.74; P=0.005). Age, sex, disease activity, disease subtype and IBD-related symptoms were not associated with PSU., Conclusions: IBD patients exhibiting PSU had increased risk of future ED visits. This study highlights the risks of PSU and reinforces the importance of appropriate substance use screening., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)