3-Year Outcomes of Balloon-Expandable Valves: 20-mm vs Larger Valves (≥23 mm).

Background: A prior Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry-based analysis reported similar 1-year clinical outcomes with small (20-mm) vs large (≥23-mm) balloon-expandable valves (BEV).

Objectives: The aim of this study was to describe mid-term 3-year clinical outcomes for small vs large BEV and the relationship between discharge echocardiographic mean gradient (MG) and different definitions of prothesis-patient mismatch (PPM) with clinical outcomes.

Methods: Using the TVT Registry with Centers for Medicare and Medicaid Services linkage, a propensity-matched analysis of patients receiving 20- vs ≥23-mm BEVs was performed.

Dual modality intravascular catheter system combining pulse-sampling fluorescence lifetime imaging and polarization-sensitive optical coherence tomography.

The clinical management of coronary artery disease and the prevention of acute coronary syndromes require knowledge of the underlying atherosclerotic plaque pathobiology. Hybrid imaging modalities capable of comprehensive assessment of biochemical and morphological plaques features can address this need. Here we report the first implementation of an intravascular catheter system combining fluorescence lifetime imaging (FLIm) with polarization-sensitive optical coherence tomography (PSOCT).

Coordinated Immune Cell Networks in the Bone Marrow Microenvironment Define the Graft versus Leukemia Response with Adoptive Cellular Therapy.

Understanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI), by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; a subset was evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population of CD8+ cytotoxic T lymphocytes (CTLs) which demonstrated specificity for autologous leukemia.

Aurora A kinase inhibition induces accumulation of SCLC tumor cells in mitosis with restored interferon signaling to increase response to PD-L1.

Despite small cell lung cancers (SCLCs) having a high mutational burden, programmed death-ligand 1 (PD-L1) immunotherapy only modestly increases survival. A subset of SCLCs that lose their ASCL1 neuroendocrine phenotype and restore innate immune signaling (termed the "inflammatory" subtype) have durable responses to PD-L1. Some SCLCs are highly sensitive to Aurora kinase inhibitors, but early-phase trials show short-lived responses, suggesting effective therapeutic combinations are needed to increase their durability.

Latent human herpesvirus 6 is reactivated in CAR T cells.

Cell therapies have yielded durable clinical benefits for patients with cancer, but the risks associated with the development of therapies from manipulated human cells are understudied. For example, we lack a comprehensive understanding of the mechanisms of toxicities observed in patients receiving T cell therapies, including recent reports of encephalitis caused by reactivation of human herpesvirus 6 (HHV-6). Here, through petabase-scale viral genomics mining, we examine the landscape of human latent viral reactivation and demonstrate that HHV-6B can become reactivated in cultures of human CD4 T cells.