ESPWA: a deep learning-enabled tool for precision-based use of endocrine therapy in resource-limited settings.

Background: Cancer morbidity disproportionately affects patients in low- and middle-income countries (LMICs), where timely and accurate tumor profiling is often nonexistent. Immunohistochemistry-based assessment of estrogen receptor (ER) status, a critical step to guide use of endocrine therapy (ET) in breast cancer, is often delayed or unavailable. As a result, ET is often prescribed empirically, leading to ineffective and toxic treatment for ER-negative patients.

Contemporary Antibody-Mediated Rejection in Heart Transplantation: JACC: Heart Failure Position Statement.

Heart transplantation remains the definitive therapy for patients with advanced heart failure. Acute and chronic rejection affect both short- and long-term outcomes. Antibody-mediated rejection (AMR) remains a leading cause of graft failure and mortality.

Two-year outcomes in the direct oral anticoagulant apixaban in left ventricular assist devices (DOAC LVAD) study.

Anticoagulation with apixaban was previously demonstrated to be feasible without excess hemocompatibility-related adverse events (HRAEs) at 6 months but longer-term data on use of apixaban is lacking. We report 2-year outcomes of patients enrolled into the DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) study. The primary study outcome was death or major HRAE (stroke, device thrombosis, major bleeding, aortic root thrombus, and/or arterial non-central nervous system thromboembolism).

CAR T-cell immunotherapy as the next horizon in cancer eradication: current landscape, challenges, and future directions.

Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a groundbreaking modality in cancer immunotherapy, offering remarkable clinical benefits, particularly in hematologic malignancies. By genetically reprogramming autologous T-cells to express synthetic receptors targeting tumor-specific antigens, CAR T-cells can mediate robust antitumor responses. This review provides a comprehensive overview of CAR T-cell immunotherapy, including its historical development, structural design, mechanism of action, and preclinical and clinical evolution.

Barriers to Immunosuppressant Medication Adherence in Thoracic Transplant Recipients: Initial Findings.

Although transplantation remains the gold-standard treatment for patients with end-organ failure, lifelong adherence to immunosuppressant medication is required to prevent rejection, graft failure, and mortality. Given the increase in thoracic organ transplantation, it is crucial to better understand the associated barriers to treatment. Examining sociodemographic, transplant, healthcare access, post-transplant treatment, and patient-related psychosocial factors may help to elucidate treatment barriers that have not been previously considered in the existing literature.

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain.

A role for the trafficking receptor SORLA in reducing Aβ levels has been well-established, however, relatively little is known with respect to whether and how SORLA can potentially affect tau pathology . Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation and seeding, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q.

Visit types and linkage to HIV prevention among individuals seeking mpox vaccination in an urban specialized sexual health clinic.

Individuals attending mpox vaccine-only visits at an STI clinic were more likely to be new patients with high socioeconomic status and identify as White than those vaccinated during non-mpox related visits. A small number received HIV PrEP or testing following vaccination; this may represent a missed opportunity for HIV prevention.

Utility of Plasma Cell-free Chromatin Immunoprecipitation to Detect Cardiac Allograft Rejection.

Background: Antibody-mediated rejection (AMR) remains the major risk factor for allograft loss across all solid organ transplantation. Unfortunately, its diagnosis relies on biopsy, an invasive gold standard that often sample unaffected allograft tissue leading to missed diagnosis. Plasma donor-derived cell-free DNA (dd-cfDNA) is noninvasive biomarker that has high sensitivity but low specificity for AMR diagnosis.

Implementing Precision Medicine for Dilated Cardiomyopathy: Insights From the DCM Consortium.

Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to genetic evaluations will enable strategies to enhance precision medicine care. Cardiologist investigators of the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs conducted an online survey in June 2024 to collect demographics, training, program characteristics, genetic evaluation practices, and implementation needs for DCM.

Summary of the International Society for Heart and Lung Transplantation consensus conference on emerging understanding of antibodies and antibody-mediated rejection in heart transplantation.

The understanding of circulating antibodies and their relationship to antibody-mediated rejection (AMR) has yet to be fully elucidated in heart transplantation. Circulating antibodies are important in both pretransplant and post-transplant. In the pretransplant period, the more antibodies detected in a patient awaiting heart transplantation often significantly reduces the chance of obtaining a compatible donor heart.

Antecedent Flu-Like Illness and Onset of Idiopathic Dilated Cardiomyopathy: The DCM Precision Medicine Study.

Background: Previous studies have speculated that a viral infection may act as a trigger in the development of idiopathic dilated cardiomyopathy (DCM) among individuals genetically at risk. This study aims to describe the frequency of patients with DCM who reported experiencing symptoms of flu-like illness before their DCM diagnosis and to examine if this experience modified the association between genetics and DCM.

Methods: We analyzed data from the family-based cross-sectional DCM Study conducted between 2016 and 2021.

Role of Hemoglobin-Stimulated Macrophages and Intraplaque Hemorrhage in the Development of Vascular Diseases.

Intraplaque hemorrhage plays a critical role in the life of advancing atherosclerotic plaques, not only by triggering an acute increase in lesion size but also by attracting macrophages to the site. Lysis of erythrocytes in these areas is thought to be caused by oxidative stress, which induces the release of free Hb (hemoglobin), which is quickly bound by haptoglobin to form Hb-haptoglobin complexes. Macrophages are the only cells in the body capable of scavenging these complexes through the CD (cluster of differentiation) 163 scavenger receptor, which mediates Hb-haptoglobin ingestion, driving their differentiation.

Sex-Based Differences in Early and Late Kidney Outcomes After Heart Transplantation.

Background: The development of kidney disease after heart transplantation (HT) has been well described and is associated with increased post-HT mortality. Limited data have evaluated sex-based differences in kidney outcomes post-HT.

Methods: Adults (≥ 18 years old) in the United Network for Organ Sharing registry who underwent HT between 2010 and 2022 were included.

Alcohol Exposure Among Patients With Dilated Cardiomyopathy and Their First-Degree Relatives: The DCM Precision Medicine Study.

Background: Whether prolonged and excessive alcohol consumption contributes to dilated cardiomyopathy (DCM) remains uncertain. This study aimed to describe the prevalence of alcohol use in patients with DCM and their first-degree relatives (FDRs) and determine if cumulative alcohol exposure associates with DCM/partial DCM or modifies the association of DCM with DCM-relevant rare variants.

Methods: All probands had DCM; FDRs were classified as with or without DCM or partial DCM.

Evaluation of Women with Peripartum or Dilated Cardiomyopathy and Their First-Degree Relatives: The DCM Precision Medicine Study.

Background: Rare variant genetics have been associated with peripartum cardiomyopathy (PPCM) but the role of genetics remains unsettled.

Objective: The study sought to compare dilated cardiomyopathy (DCM) genetic risk in first-degree relatives (FDRs) of female patients with DCM or PPCM (probands), and to assess DCM-relevant rare variant prevalence in DCM/PPCM probands and population controls.

Methods: Clinical and genetic data were analyzed from the DCM Precision Medicine Study.

The Society of Thoracic Surgeons National Intermacs Database Risk Model for Durable Left Ventricular Assist Device Implantation.

Background: Statistical risk models for durable left ventricular assist device (LVAD) implantation inform candidate selection, quality improvement, and evaluation of provider performance. This study developed a 90-day mortality risk model using The Society of Thoracic Surgeons National Intermacs Database (STS Intermacs).

Methods: STS Intermacs was queried for primary durable LVAD implants from January 2019 to September 2023.

Exploring Dental Trauma Among Cattle Farmers in Vadodara, Gujarat: Prevalence and Risk Factors.

Background: Traumatic dental injuries (TDI) are a global health concern, affecting millions of people annually. The prevalence of traumatic dental injuries (TDIs) can vary significantly with change in geographic region, occupation, and lifestyle. Animal handlers, such as cattle farmers, are at risk of experiencing TDIs due to their interactions with animals.

Preliminary clinical performance of a Cas13a-based lateral flow assay for detecting in urine specimens.

Nucleic acid amplification testing (NAAT) for is unavailable in resource-limited settings. We previously developed a CRISPR-based lateral flow assay for detecting . We aimed to pair that assay with point-of-care DNA extraction, assess performance in clinical urine specimens, and optimize assay kinetics.

Risk Factors Favoring Plaque Erosion.

Purpose Of Review: Plaque erosion is the second leading cause of coronary thrombosis following plaque rupture and represents a key pathophysiological process underlying acute coronary syndromes that can culminate in sudden coronary death. While the precise mechanisms and risk factors driving plaque rupture are well-established, those for erosion have only recently been explored. This review summarizes current literature on the characteristics and risk factors favoring plaque erosion.

Implementing Precision Medicine for Dilated Cardiomyopathy: Insights from The DCM Consortium.

Background: Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to genetic evaluations will enable strategies to enhance precision medicine care.

Methods: An online survey was conducted in June 2024 among cardiologist investigators of the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs to collect demographics, training, program characteristics, genetic evaluation practices for DCM, and implementation needs.

Proteomics in Acute Heart Transplant Rejection, on Behalf of the GRAfT Investigators.

Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).