Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D.

Background And Objective: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC.

Methods: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide.

Adapting the World Health Organization's Surgical Safety Checklist to High-Income Settings: A Hybrid Effectiveness-Implementation Trial Protocol.

Objectives: The proposed study aims to assess users' perceptions of a surgical safety checklist (SSC) reimplementation toolkit and its impact on SSC attitudes and operating room (OR) culture, meaningful checklist use, measures of surgical safety, and OR efficiency at 3 different hospital sites.

Background: The High-Performance Checklist toolkit (toolkit) assists surgical teams in modifying and implementing or reimplementing the World Health Organization's SSC. Through the explore, prepare, implement, and sustain implementation framework, the toolkit provides a process and set of tools to facilitate surgical teams' modification, implementation, training on, and evaluation of the SSC.

SHIP inhibition mediates select TREM2-induced microglial functions.

Microglia play a pivotal role in the pathology of Alzheimer's Disease (AD), with the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) central to their neuroprotective functions. The R47H variant of TREM2 has emerged as a significant genetic risk factor for AD, leading to a loss-of-function phenotype in mouse AD models. This study elucidates the roles of TREM2 in human microglia-like HMC3 cells and the regulation of these functions by SH2-containing inositol-5'-phosphatase 1 (SHIP1).

Updated 5-year results for short course abiraterone acetate and LHRH agonist for unfavorable intermediate and favorable high-risk prostate cancer.

Combined androgen deprivation therapy (ADT) and radiotherapy (RT) improves outcomes for intermediate and high-risk prostate cancer. Treatment intensification with abiraterone acetate/prednisone (AAP) provides additional benefit for high-risk disease. We previously reported 3-year outcomes of a single-arm prospective multicenter trial (AbiRT trial) of 33 patients with unfavorable intermediate risk (UIR) and favorable high risk (FHR) prostate cancer undergoing short course, combination therapy with ADT, AAP, and RT.

Development, implementation and impact of an immunoglobulin stewardship programme in Saskatchewan, Canada.

Background And Objectives: Intravenous immunoglobulin (IVIG) is one of the most costly and limited-supply blood products. Judicious use of this therapy is important to ensure a continued supply is available for patients in need. The Saskatchewan IG Stewardship Program was initiated to monitor and reduce inappropriate IG use.

Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study.

Background: Limited responses have been observed in patients treated with enzalutamide after disease progression on abiraterone for metastatic castration-resistant prostate cancer (mCRPC), but androgen receptor signaling impacts T-cell function.

Objective: To evaluate the efficacy and safety of pembrolizumab plus enzalutamide in mCRPC.

Design, Setting, And Participants: Patients in cohort C of the phase 1b/2 KEYNOTE-365 study, who received ≥4 wk of treatment with abiraterone acetate in the prechemotherapy mCRPC state and experienced treatment failure or became drug-intolerant, were included.

Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer.

Ovarian cancer (OvCa) has a dismal prognosis because of its late-stage diagnosis and the emergence of chemoresistance. Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase known to regulate cancer cell "stemness", epithelial-mesenchymal transition (EMT), and drug resistance. Here we show that DCLK1 is a druggable target that promotes chemoresistance and tumor progression of high-grade serous OvCa (HGSOC).

CheckPOINT: a simple tool to measure Surgical Safety Checklist implementation fidelity.

Introduction: The WHO Surgical Safety Checklist (SSC) is a communication tool that improves teamwork and patient outcomes. SSC effectiveness is dependent on implementation fidelity. Administrative audits fail to capture most aspects of SSC implementation fidelity (ie, team communication and engagement).

Attitudes towards HPV Vaccination Policy Strategies to Improve Adolescent Vaccination Coverage among Pediatric Providers in New York State.

Pediatric providers' stances on HPV vaccination-related policies are largely unknown. To gain insight into pediatric providers' perspectives and potential recommendations for directed policy, we conducted a cross-sectional survey of the American Academy of Pediatrics members in New York. Almost all providers expressed confidence in discussing the HPV vaccine with patients (98.

FGF1 supports glycolytic metabolism through the estrogen receptor in endocrine-resistant and obesity-associated breast cancer.

Background: Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk.

Associations between gynecologic clinician type and routine female sexual dysfunction screening.

Background: Female sexual dysfunction (FSD) is a common problem in the United States; however, only 14% to 40% of women are screened by their health care clinicians. There are few data on how differences in clinician type affects screening rates.

Aim: This study aimed to assess differences in FSD screening rates among gynecology clinician types, identify factors associated with screening, and compare screening rates of FSD against conditions with established screening recommendations.

Determining the validity of non-invasive spot-check hemoglobin co-oximetry testing to detect anemia in postpartum women at a tertiary care centre, a prospective cohort study.

Background: Spot-check hemoglobin co-oximetry analyzers measure hemoglobin transcutaneously and offer the benefit of a hemoglobin measurement without phlebotomy. The objective of this study was to determine the validity of non-invasive spot-check hemoglobin co-oximetry testing for the detection of postpartum anemia (hemoglobin < 10 g/dL).

Methods: Five hundred eighty-four women aged 18 and over were recruited on postpartum day one following a singleton delivery.

Defining re-implementation.

Background: The first attempt to implement a new tool or practice does not always lead to the desired outcome. Re-implementation, which we define as the systematic process of reintroducing an intervention in the same environment, often with some degree of modification, offers another chance at implementation with the opportunity to address failures, modify, and ultimately achieve the desired outcomes. This article proposes a definition and taxonomy for re-implementation informed by case examples in the literature.

What I wish I'd known: How experienced physician managers diagnose, treat and prevent disruptive behaviour.

As health systems continue to consolidate at a rapid pace, many physicians are stepping into roles that involve managing other physicians. While more physicians are thrust into these positions each year, the managerial training they receive is highly variable and often insufficient for dealing with the challenges they will face, notably disruptive behaviour. Broadly defined, disruptive behaviour includes any actions that affect a team's ability to effectively care for patients, and can even threaten patient and provider health.

Multifunctional Microgel-Based Cream Hydrogels for Postoperative Abdominal Adhesion Prevention.

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, antioxidation, anti-inflammation, and anti-cell adhesion.

KRCC1, a modulator of the DNA damage response.

The lysine-rich coiled-coil 1 (KRCC1) protein is overexpressed in multiple malignancies, including ovarian cancer, and overexpression correlates with poor overall survival. Despite a potential role in cancer progression, the biology of KRCC1 remains elusive. Here, we characterize the biology of KRCC1 and define its role in the DNA damage response and in cell cycle progression.

Temporal control of PDGFRα regulates the fibroblast-to-myofibroblast transition in wound healing.

Fibroblasts differentiate into myofibroblasts by acquiring new contractile function. This is important for tissue repair, but it also contributes to organ fibrosis. Platelet-derived growth factor (PDGF) promotes tissue repair and fibrosis, but the relationship between PDGF and myofibroblasts is unclear.

Determining Intestinal Permeability using Lucifer Yellow in an Apical-Out Enteroid Model.

Enteroids are an emerging research tool in the study of inflammatory bowel diseases such as necrotizing enterocolitis (NEC). They are traditionally grown in the basolateral-out (BO) conformation, where the apical surface of the epithelial cell faces the inner lumen. In this model, access to the luminal surface of enteroids for treatment and experimentation is challenging, which limits the ability to study host-pathogen interactions.

Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study.

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments.

Objective: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC.

Design, Setting, And Participants: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening.

Improving communication and teamwork during labor: A feasibility, acceptability, and safety study.

Background: TeamBirth was designed to promote best practices in shared decision making (SDM) among care teams for people giving birth. Although leading health organizations recommend SDM to address gaps in quality of care, these recommendations are not consistently implemented in labor and delivery.

Methods: We conducted a mixed-methods trial of TeamBirth among eligible laboring patients and all clinicians (nurses, midwives, and obstetricians) at four high-volume hospitals during April 2018 to September 2019.

Examining health care champions: a mixed-methods study exploring self and peer perspectives of champions.

Background: Champions are widely recognized as playing a key role in the successful implementation of evidence-based interventions within the health care sector; however, little is known about which characteristics and skills enable them to play that role. Furthermore, previous studies have measured only individual champions' responses to personal attributes without incorporating input from other observers. A mixed-methods study was conducted to identify, analyze, and group the behaviors and characteristics of champions who have successfully promoted the adoption of new initiatives within the health care delivery system, taking into consideration self and peer perspectives.