A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.

The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

Subclinical Myocardial Fibrosis in South African Youth With HIV: Results From the CTAAC-Heart Study.

Background: Few data exist on myocardial fibrosis and inflammation in youth with HIV.

Methods: We performed cardiovascular magnetic resonance (CMR) on a cross section of South African youth: youth with perinatally acquired HIV (YPHIV) undergoing antiretroviral therapy (ART), youth with nonperinatally acquired HIV (YNPHIV) receiving ART, and youth without HIV. Quantile regression models were fit to assess the association between HIV status and CMR outcomes: subclinical fibrosis (late gadolinium enhancement [LGE] mass and fraction, native T1, extracellular volume) and inflammation (native T1, T2 mapping).

An integrated approach to neuroscience care: An innovative model to support the new integrated care system.

Integrated care systems join up health and care services, so that people have the support they need, in the right place, at the right time. The aims include improving outcomes in healthcare, tackling inequalities in access and enhancing productivity and value for money. This is needed for neuroscience care as the traditional delivery of neuroscience care is inefficient, outdated and expensive, and can involve complex referral pathways and long waiting times.

BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes.

T cell co-inhibitory immune checkpoints, such as PD-1 or BTLA, are bona fide targets in cancer therapy. We used a human T cell reporter line to measure transcriptomic changes mediated by PD-1- and BTLA-induced signaling. T cell receptor (TCR)-complex stimulation resulted in the upregulation of a large number of genes but also in repression of a similar number of genes.

A novel colorectal cancer test combining microsatellite instability and analysis: Clinical validation and impact on Lynch syndrome screening.

Background: Lynch syndrome (LS) is under-diagnosed. UK National Institute for Health and Care Excellence guidelines recommend multistep molecular testing of all colorectal cancers (CRCs) to screen for LS. However, the complexity of the pathway has resulted in limited improvement in diagnosis.

When Are "Paraphernalia" Critical Medical Supplies?

Evidence of harm reduction interventions' morbidity and mortality benefits is abundant and of high quality, so there are good reasons for regional and national groups to advocate for more widespread distribution of legally regulated "drug paraphernalia," including needles, syringes, and fentanyl test strips. But lack of consistency among states' laws means that patients' interstate travel can subject them to being charged with possession of illegal items. This commentary on a case offers guidance to clinicians looking to help patients understand legal risks of interstate travel with supplies that are prescribed or recommended to reduce harms of their drug use and explores the ethical responsibilities of physicians in jurisdictions that legally prohibit these harm reduction interventions.

Hawks and Doves in Standardized Letters of Evaluation: 6 Years of Rating Distributions and Trends in Emergency Medicine.

Standardized Letters of Evaluation (SLOEs) are an important part of resident selection in many specialties. Often written by a group, such letters may ask writers to rate applicants in different domains. Prior studies have noted inflated ratings; however, the degree to which individual institutions are "doves" (higher rating) or "hawks" (lower rating) is unclear.

IQ in high school as a predictor of midlife alcohol drinking patterns.

Aims: The aim of the present study was to assess the relationship between adolescent IQ and midlife alcohol use and to explore possible mediators of this relationship.

Methods: Study data were from 6300 men and women who participated in the Wisconsin Longitudinal Study of high-school students graduating in 1957. IQ scores were collected during the participants' junior year of high school.

Greater Disease Severity and Worse Clinical Outcomes in Patients Hospitalised with COVID-19 in Africa.

Background: COVID-19 cardiovascular research from Africa is limited. This study describes cardiovascular risk factors, manifestations, and outcomes of patients hospitalised with COVID-19 in the African region, with an overarching goal to investigate whether important differences exist between African and other populations, which may inform health policies.

Methods: A multinational prospective cohort study was conducted on adults hospitalised with confirmed COVID-19, consecutively admitted to 40 hospitals across 23 countries, 6 of which were African countries.

Measuring Emergency Department Workload Perception Using Electronic Medical Record Measures of Patient Volume and Acuity.

Background: Workload in the emergency department (ED) fluctuates and there is no established model for measurement of clinician-level ED workload.

Objective: The aim of this study was to measure perceived ED workload and assess the relationship between perceived workload and objective measures of workload from the electronic medical record (EMR).

Methods: This study was conducted at a tertiary care, academic ED from July 1, 2020 through April 13, 2021.

The utility of an online discussion board for reflective writing in an emergency medicine rotation.

Background: Narrative analysis and reflection have been found to support professional identity formation (PIF) and resilience among medical students. In the emergency department, students have used reflective practice to process challenging clinical experiences, such as ethical dilemmas or moral distress. An online discussion board, however, has not been described as a curricular component of emergency medicine (EM) rotations.

Deciphering the tumour immune microenvironment cell by cell.

Immune checkpoint inhibitors (ICIs) have rejuvenated therapeutic approaches in oncology. Although responses tend to be durable, response rates vary in many cancer types. Thus, the identification and validation of predictive biomarkers is a key clinical priority, the answer to which is likely to lie in the tumour microenvironment (TME).

Variability in Emergency Department Procedure Rates and Distributions in a Regional Health System: A Cross-Sectional Observational Study.

Study Objective: Procedural competency is essential to the practice of emergency medicine. However, there are limited data quantifying emergency department procedural volumes to inform the work of educators and credentialing bodies. In this study, we characterize procedural scope and volume in a regional health care system and compare rates between practice settings and over time.

CRABP2 - A novel biomarker for high-risk endometrial cancer.

Objective: Investigate the clinical and functional implications of elevated CRABP2 expression in endometrial cancer (EC) patients.

Methods: Patients were stratified into high and low CRABP2 expression groups using a decision tree classifier. Univariate and multivariate statistical analyses determined the prognostic and clinicopathological consequences of increased CRABP2 expression.

The Emergency Medicine Resident Retreat: Creating and Sustaining a Transformative and Reflective Experience.

Introduction  Burnout rates for emergency medicine residents are high. One intervention and initiative to enhance wellness and address burnout is the resident retreat. Retreats have multiple formats and are often designed with an emphasis on social events.

The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome.

Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone.