Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN.

Background: In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of >3 years.

A systematic scoping review of interventions to integrate physical and mental healthcare for people with serious mental illness and substance use disorders.

Integrated care approaches have been recommended to remove barriers to healthcare and improve the physical health outcomes of people living with serious mental illness (SMI) and/or substance use disorders (SUDs). The aim of this systematic scoping review was to describe empirical investigations of interventions designed to integrate physical, mental, and addiction healthcare for this population. An iterative and systematic search of five electronic databases (Medline (Ovid), PsycINFO, CINAHL, Embase (Ovid) and Scopus) was conducted to identify peer-reviewed articles published between January 2000 and April 2019.

Pharmacogenomic-Based Decision Support to Predict Adherence to Medications.

Poor adherence is associated with worse disease outcomes. Pharmacogenomics provides a possible intervention to address adherence. We hypothesized that pharmacogenomic-informed care could increase adherence.

Characteristics and outcomes of maternal cardiac arrest: A descriptive analysis of Get with the guidelines data.

Background: Maternal mortality has risen in the United States in the twenty-first century, yet large cohort data of maternal cardiac arrest (MCA) are limited.

Objective: We sought to describe contemporary characteristics and outcomes of in-hospital MCA.

Methods: We queried the American Heart Association's Get with the Guidelines Resuscitation voluntary registry from 2000 to 2016 to identify cases of maternal cardiac arrest.

Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial.

Objectives: Clostridium difficile infection (CDI) is a major public health concern. Treatment with commonly prescribed antibiotics is associated with high rates of recurrence after initial cure. Here, we present the efficacy and safety of surotomycin, an orally administered, minimally absorbed, selective bactericidal cyclic lipopeptide, compared with vancomycin, in patients with CDI.

Regulation of Smad-mediated gene transcription by RGS3.

Regulator of G protein signaling (RGS) proteins are united into a family by the presence of the homologous RGS domain that binds the alpha subunits of heterotrimeric G proteins and accelerates their GTPase activity. A member of this family, RGS3 regulates the signaling mediated by G(q) and G(i) proteins by binding the corresponding Galpha subunits. Here we show that RGS3 interacts with the novel partners Smad2, Smad3, and Smad4-the transcription factors that are activated through a transforming growth factor-beta (TGF-beta) receptor signaling.

Regulation of serum response factor-dependent gene expression by proteasome inhibitors.

Serum response factor (SRF) is activated by contractile and hypertrophic agonists, such as endothelin-1 (ET1) to stimulate expression of cytoskeletal proteins in vascular smooth muscle cells (VSMCs). While studying the regulation of smooth muscle alpha-actin (SMA) expression at the level of protein stability, we discovered that inhibition of proteasome-dependent protein degradation by N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) or lactacystin (LC) did not enhance the levels of SMA, but, unexpectedly, attenuated SMA expression in response to ET1, without affecting the viability of VSMCs. Down-regulation of SMA protein by MG132 or LC occurred at the level of SMA transcription and via the inhibition of SRF activity.