Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus.

Objective: Despite substantial advances in the treatment of systemic lupus erythematosus (SLE), some patients do not respond to the current state-of-the art therapies. This study assessed the tolerability and efficacy of CD19 chimeric antigen receptor (CAR) T cells in a small series of seriously ill and treatment-resistant patients with SLE.

Methods: Five patients with SLE (four female patients and one male patient) with a median age of 22 (range 18-24) years, a median disease duration of 4 (range 1-9) years, and active disease (median Systemic Lupus Erythematosus Disease Activity Index score of 16 [range 8-16]) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use CAR-T cell program.

Disasters in the Northern Triangle: A Descriptive Analysis Using the EM-DAT Database 1902-2022.

Introduction: Since 1902, disasters in the Northern Triangle of Central America, which consists of the countries Guatemala, Honduras, and El Salvador, have caused over one-hundred-thousand deaths, affected millions of people, and caused tens of billions of dollars in damages. Understanding the nature and frequency of these events will allow stakeholders to decrease both the acute damages and the long-term deleterious consequences of disasters.

Study Objective: This study provides a descriptive analysis of all disasters recorded in the Emergency Events Database (EM-DAT) affecting Guatemala, Honduras, and El Salvador from 1902-2022.

COVID-19, Obesity, and GRP78: Unraveling the Pathological Link.

The coronavirus disease 2019 (COVID-19) pandemic, driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an unprecedented global surge in infections and fatalities. Notably, obesity has emerged as an important susceptibility factor for COVID-19; however, the pathological mechanisms for this remain poorly understood. Recent studies proposed a role for glucose-regulated protein 78 (GRP78), a protein implicated in both obesity and metabolic syndrome, which may function as a binding partner and/or co-receptor for SARS-CoV-2.

Biological sex divergence in transcriptomic profiles during the onset of hindlimb unloading-induced atrophy.

Disuse-induced muscle atrophy is a common clinical problem observed mainly in older adults, intensive care units patients, or astronauts. Previous studies presented biological sex divergence in progression of disuse-induced atrophy along with differential changes in molecular mechanisms possibly underlying muscle atrophy. The aim of this study was to perform transcriptomic profiling of male and female mice during the onset and progression of unloading disuse-induced atrophy.

Optimizing Informed Consent Discussions: Developing a Narrative for Transfusion Consent.

Ensuring patient informed consent is a key tenet of modern medicine. Although transfusion of blood products is among the most common medical procedures performed in hospitalized patients, there is evidence that informed consent for transfusion is at times incomplete, poorly understood, hurried, and/or inaccurate. This study aimed to develop a narrative that can be used as a framework for practicing physicians and for educational purposes to optimize the process for obtaining informed consent for blood transfusion.

Adenosine A receptors and sleep.

Adenosine, a known endogenous somnogen, induces sleep via A and A receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A receptor agonists, antagonists, and allosteric modulators have been identified, only a few have been tested to see if they can promote sleep or wakefulness.

Periprocedural management of type 2N von Willebrand disease with efanesoctocog alfa.

Type 2 Normandy von Willebrand disease (type 2N VWD) is a rare qualitative defect in von Willebrand factor (VWF) that results in impaired factor VIII (FVIII) binding and consequently reduced FVIII levels. Current perioperative strategies require VWF concentrates to attain durable hemostatic FVIII levels. This case highlights the successful perioperative management of a 78-year-old female with type 2N VWD and coronary artery disease utilizing efanesoctocog alfa, a novel long-acting recombinant FVIII product approved for hemophilia A.

Proceedings of a Workshop to Promote Community Health Worker Interventions in Nephrology.

Latinx populations face a higher burden of kidney failure and associated negative outcomes compared with non-Latinx White populations, despite sharing a similar prevalence of CKD. Community health worker (CHW) interventions have been shown to improve outcomes for Latinx individuals, but they are largely underutilized in kidney disease. We convened a workshop of four ongoing kidney disease CHW programs to identify successes, challenges, potential solutions, and needed research to promote CHW programs for Latinx individuals with kidney disease.

Identification of the glycopeptide epitope recognized by a protective monoclonal antibody.

species are a leading cause of pediatric diarrheal disease and death in low- and middle-income countries and pose a particular threat to immunocompromised individuals. As a zoonotic pathogen, can have devastating effects on the health of neonatal calves. Despite its impact on human and animal health, consistently effective drug treatments for cryptosporidiosis are lacking and no vaccine is available.

Integrating palliative care into the evolving landscape of oncology.

Patients with cancer have many palliative care needs. Robust evidence supports the early integration of palliative care into the care of patients with advanced cancer. International organizations, such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), have recommended early, longitudinal integration of palliative care into oncology care throughout the cancer trajectory.

Prognostic microRNA signature for estimating survival in patients with hepatocellular carcinoma.

Objective: Hepatocellular carcinoma (HCC) is one of the leading cancer types with increasing annual incidence and high mortality in the USA. MicroRNAs (miRNAs) have emerged as valuable prognostic indicators in cancer patients. To identify a miRNA signature predictive of survival in patients with HCC, we developed a machine learning-based HCC survival estimation method, HCCse, using the miRNA expression profiles of 122 patients with HCC.

The effect of duration of untreated psychosis (DUP) on the risk for hospitalization after admission to a first episode service.

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore associations between patients' characteristics and hospitalization post-FES.

Pathophysiology updates: gastroduodenal injury and repair mechanisms.

Purpose Of Review: Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.

Recent Findings: Recent studies on acute superficial lesions have focused on calcium signaling and focal adhesion kinase, which regulate cell migration and controlled matrix adhesion during restitution. Microfluidic organ-on-a-chip and gut-on-a-chip models continued in development to support reductionist studies of epithelial-bacterial and/or epithelial-immune cell interactions during mucosal barrier disruption.

A pilot clinical skills coaching program to reimagine remediation: a cohort study.

Background New approaches are needed to improve and destigmatize remediation in undergraduate medical education (UME).  The COVID-19 pandemic magnified the need to support struggling learners to ensure competency and readiness for graduate medical education (GME).  Clinical skills (CS) coaching is an underutilized approach that may mitigate the stigma of remedial learning.

Demethylation of EHMT1/GLP Protein Reprograms Its Transcriptional Activity and Promotes Prostate Cancer Progression.

Unlabelled: Epigenetic reprogramming, mediated by genomic alterations and dysregulation of histone reader and writer proteins, plays a critical role in driving prostate cancer progression and treatment resistance. However, the specific function and regulation of EHMT1 (also known as GLP) and EHMT2 (also known as G9A), well-known histone 3 lysine 9 methyltransferases, in prostate cancer progression remain poorly understood. Through comprehensive investigations, we discovered that both EHMT1 and EHMT2 proteins have the ability to activate oncogenic transcription programs in prostate cancer cells.

Clinical characterization and differentiation of B-SNIP psychosis Biotypes: Algorithmic Diagnostics for Efficient Prescription of Treatments (ADEPT)-1.

Clinically defined psychosis diagnoses are neurobiologically heterogeneous. The B-SNIP consortium identified and validated more neurobiologically homogeneous psychosis Biotypes using an extensive battery of neurocognitive and psychophysiological laboratory measures. However, typically the first step in any diagnostic evaluation is the clinical interview.

Diagnostic Pitfalls in Breast Cancer Pathology With an Emphasis on Core Needle Biopsy Specimens.

Context.—: Breast pathology has many mimics and diagnostic pitfalls. Evaluation of malignant breast lesions, particularly in the biopsy setting, can be especially challenging, with diagnostic errors having significant management implications.

Pharmaco-disparities in heart failure: a survey of the affordability of guideline recommended therapy in 10 countries.

Aims: Heart failure with reduced ejection fraction (HFrEF) is treatable but guideline-directed medical therapy (GDMT) may not be affordable or accessible to people living with the disease.

Methods And Results: In this cross-sectional survey, we investigated the price, affordability, and accessibility of four pivotal classes of HFrEF GDMT: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin-neprilysin inhibitors (ARNI); beta-blockers; mineralocorticoid receptor antagonists (MRA); and sodium glucose co-transporter 2 inhibitors (SGLT2i). We sampled online or community pharmacies in 10 countries across a range of World Bank income groups, assessing mean 30 day retail prescription prices, affordability relative to gross national income per capita per month, and accessibility.

Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.

Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient-derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes.