Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.

Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017.

Background: Therapeutic strategies to engage anti-tumor innate immunity are still underdeveloped. Imprime PGG (imprime), a pathogen-associated molecular pattern (PAMP), through pattern recognition receptors, successfully illicit a broad-based innate immune response in preclinical models against various cancers. We aimed to study safety and efficacy of imprime in combination with pembrolizumab in advanced stage non-small cell lung cancer (NSCLC).

Clinical Utility of a Circulating Tumor Cell-Based Cerebrospinal Fluid Assay in the Diagnosis and Molecular Analysis of Leptomeningeal Disease in Patients With Advanced Non-Small Cell Lung Cancer.

Purpose: Leptomeningeal disease (LMD) is associated with significant morbidity and mortality for metastatic non-small cell lung cancer (NSCLC). We describe our clinical experience in evaluating the use of cerebrospinal fluid (CSF)-derived circulating tumor cells (CTCs) for the diagnosis of LMD and the detection of genomic alterations in CSF cell-free DNA (cfDNA).

Methods: Patients with NSCLC who had CSF collection as part of routine clinical care for suspected LMD were included in the study.

Opioid use patterns following discharge from elective colorectal surgery: a prospective cohort study.

Introduction: Opioid overprescription after colorectal surgery can lead to adverse events, persistent opioid use, and diversion of unused pills. This study aims to assess the extent to which opioids prescribed at discharge after elective colorectal surgery are consumed by patients.

Methods: This prospective cohort study included adult patients (≥ 18 yo) undergoing elective colorectal surgery at two academic hospitals in Montreal, Canada.

Coronary Disease Risk Prediction, Risk Reduction, and Postoperative Myocardial Injury.

For patients considering surgery, the preoperative evaluation allows physicians to identify and treat acute cardiac conditions before less-urgent surgery, predict the benefits and harms of a proposed surgery, and make temporary management changes to reduce operative risk. Multiple risk prediction tools are reasonable for use in estimating perioperative cardiac risk, but management changes to reduce risk have proven elusive. For all but the most urgent surgical procedures, patients with active coronary syndromes or decompensated heart failure should have surgery postponed.