Surgical versus Transcatheter Aortic Valve Replacement in Patients 65 Years of Age and Older.

Background: Approval of transcatheter aortic valve replacement (TAVR) for all risk profiles has extended TAVR use in patients not otherwise examined in clinical trials. We sought to evaluate contemporary real-world outcomes of surgical aortic valve replacement (SAVR) vs TAVR in Medicare beneficiaries by risk strata.

Methods: Using the United States Centers for Medicare Services database, all patients aged 65-85 undergoing isolated first-time SAVR (n=34,215) or TAVR (n=124,897) were evaluated (2018-2022).

Sex specific disruptions in Protein Kinase Cγ signaling in a mouse model of Spinocerebellar Ataxia Type 14.

Unlabelled: Spinocerebellar Ataxia Type 14 (SCA14) is an autosomal dominant neurodegenerative disease caused by mutations in the gene encoding protein kinase C gamma (PKCγ), a Ca /diacylglycerol (DG)-dependent serine/threonine kinase dominantly expressed in cerebellar Purkinje cells. These mutations impair autoinhibitory constraints to increase the basal activity of the kinase, resulting in deficits in the cerebellum that are not observed upon simple deletion of the gene, and severe ataxia. To better understand the phenotypic impact of aberrant PKCγ signaling in disease pathology, we developed a knock-in murine model of the SCA14 mutation ΔF48 in PKCγ.

Minimally Invasive Valve Surgery for Patients With Infective Endocarditis: A Comparative Study.

Background: Patients with endocarditis frequently require valve surgical procedure, and despite the recent growth of minimally invasive cardiac surgery (MICS) for complex valve operations, consensus recommendations still suggest conventional sternotomy.

Methods: The institutional Adult Cardiac Surgery Database of The Society of Thoracic Surgeons (STS) evaluated all patients undergoing valve surgical procedure for endocarditis from July 2016 to March 2024. Patients were stratified by conventional sternotomy vs an MICS approach, including hemisternotomy, right thoracotomy, and robotic-assisted mitral, tricuspid, or aortic valve surgical procedure.

The influence of prestroke disability on outcome in patients with a low Alberta Stroke Program Early CT Score who underwent endovascular thrombectomy.

Objective: The definitive influence of prestroke disability on outcomes in patients with a low Alberta Stroke Program Early CT Score (ASPECTS) treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) remains unknown. This study aimed to investigate the impact of prestroke disability on outcomes in this specific population.

Methods: Data from 32 international centers for AIS-LVO patients with a low ASPECTS who underwent EVT between January 2013 and December 2022 were analyzed retrospectively.

Preoperative Ultrasound Correctly Localized Peripheral Nerve Abnormalities for Operative Guidance: A Retrospective Review.

Background: Correct localization and characterization of nerve abnormality is of critical importance to appropriate intervention. Ultrasound (US) is known to be accurate in the diagnosis of peripheral neuropathy and in preoperative localization of nerve abnormalities and skin marking.

Purpose: We sought to investigate the utility of US-guided preoperative skin marking for the localization of peripheral nerve abnormality and to compare the US findings to electrodiagnostic (EDx) reports.

Comparative efficacy and safety of stent retrievers as a bailout strategy following failed contact aspiration technique in acute stroke thrombectomy.

Background: The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA.

Methods: EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy.

Mechanical thrombectomy in elderly stroke patients with low ASPECTS: insights from STAR.

Background: The elderly population (≥80 years) were underrepresented in recent trials of endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) with low Alberta Stroke Program Early CT Score (ASPECTS) (≤5).

Methods: This study analyzed data from a prospectively maintained database of 37 thrombectomy centers. The primary cohort of the study comprised patients with LVO-AIS aged ≥80 who underwent EVT with ASPECTS≤5 from 2013 to 2023.

Utilizing Quantitative Analysis of CSF Volume from Clinical T1-Weighted MRI to Predict Thrombectomy Outcomes.

Background And Purpose: Endovascular thrombectomy (EVT) is the standard for acute ischemic stroke from large vessel occlusion, but post-EVT functional independence varies. Brain atrophy, linked to higher cerebrospinal fluid volume (CSFV), may affect outcomes. Baseline CSFV could predict EVT benefit by assessing brain health.

Advances in Topical Therapies for Clinically Relevant and Prevalent Forms of Alopecia.

Alopecia encompasses diverse conditions that vary by etiology, progression, and clinical presentation, including androgenetic alopecia, alopecia areata, telogen effluvium, and scarring alopecias such as lichen planopilaris and central centrifugal cicatricial alopecia. Managing these conditions requires tailored therapeutic approaches, with topical treatments emerging as effective first-line interventions. This literature review examines topical therapies across alopecia types, assessing mechanisms of action, clinical efficacy, and safety profiles to guide evidence-based clinical practice.

Direct delivery of Cas-embedded cytosine base editors as ribonucleoprotein complexes for efficient and accurate editing of clinically relevant targets.

Recently, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite this promise, the currently available CBEs have the significant liabilities of off-target and bystander editing activities, partly due to the mechanism by which they are delivered, causing limitations in their potential applications. In this study, we engineered optimized, soluble and stable Cas-embedded CBEs (CE_CBEs) that integrate several recent advances, which were efficiently formulated for direct delivery into cells as ribonucleoprotein (RNP) complexes.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Outcomes of Adjunct Emergent Stenting Versus Mechanical Thrombectomy Alone: The RESCUE-ICAS Registry.

Background: Underlying intracranial stenosis is the most common cause of failed mechanical thrombectomy in patients with acute ischemic stroke with large vessel occlusion. Adjunct emergent stenting is sometimes performed to improve or maintain reperfusion, despite limited data regarding its safety or efficacy.

Methods: We conducted a prospective multicenter observational international cohort study.

The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling.

Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion oncoprotein CBFβ::MYH11 regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion.

Predicting poor functional outcomes for patients with large computed tomography perfusion core infarctions treated with endovascular thrombectomy.

Objective: Stroke patients with large core infarctions benefit from endovascular intervention, though only approximately 20% are functionally independent at 90 days. We studied prognostic factors for patients presenting with a large computed tomography perfusion (CTP) core.

Methods: Retrospective analysis from a health system stroke registry, including consecutive thrombectomy patients treated within 24 hours from August 2020-December 2022 with an anterior circulation large vessel occlusion and CTP core infarct ≥50 milliliters.

Our Health Counts Toronto: Commercial tobacco use among Indigenous peoples in Toronto.

Objective: Fueled by the commercial tobacco industry, commercial tobacco use continues to be the leading preventable cause of premature death in Canada, with opportunities to improve health outcomes. The objective of this research was to work with Indigenous partners to generate Indigenous population prevalence estimates of commercial tobacco use in Toronto, and examine the association between smoking and sociodemographic, cultural, resiliency, and social variables.

Methods: Respondent-driven sampling (RDS) was used to generate prevalence estimates of commercial tobacco use and potentially associated sociodemographic, cultural, resiliency, and social connection variables for Indigenous adults living in Toronto.

Round table discussion. The management of proximal scaphoid nonunion.

The management of scaphoid nonunion, although relatively common, continues to pose challenges, especially if complicated by avascular necrosis of the proximal pole, humpback or dorsal intercalated segment instability deformities, and early scaphoid nonunion advanced collapse. In this round table article, four surgeons were asked to answer key questions on a clinical example of a proximal scaphoid nonunion to outline their approach and rationale in their preferred treatment choices. The current panel of experts leans towards arthroscopic methods of treatment and most agree that arthroscopic bone grafting has become an important and revolutionary treatment option, which has yielded excellent results.

Pemphigus relapse: Mechanisms, risk factors, and agents associated with disease recurrence.

Pemphigus represents a spectrum of potentially life-threatening autoimmune-mediated skin blistering conditions caused by antibody production against desmoglein 1 and 3 (anti-DSG 1 and 3) in keratinocytes. Greater than 50% of pemphigus patients experience relapse, which complicates long-term medical management, including risks associated with re-treatment and complications such as infection and dehydration. This review aims to elucidate mechanisms, risk factors, and medications associated with pemphigus relapse.

Early Renal Outcomes Following Heart Transplantation Using Organs Procured After Circulatory Death.

Background: Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited.

Methods And Results: Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation.