Elevation of Granulocyte Colony Stimulating Factor in Human AMD Donor RPE-Choroid.

Purpose: Choroidal inflammation, complement deposition, and accumulation of C-reactive protein (CRP) are involved in age-related macular degeneration (AMD) pathology. The pro-inflammatory signals that regulate immune cell recruitment in the choroid of patients with AMD remain to be determined. We performed cytokine profiling of human AMD and age-matched control donor tissue to identify inflammatory molecules upregulated in AMD tissue.

Diastolic Dysfunction and the Risk of Stroke and Major Bleeding.

Background: Left ventricular diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident stroke and transient ischemic attack (TIA) and with bleeding events is not known. We performed this observational cohort analysis to examine the impact of DD on the risk of stroke/TIA and major bleeding.

Combined left atrial appendage occlusion and catheter ablation procedure for left atrial arrhythmias: A real-world, propensity-matched analysis.

Introduction: Real-world studies comparing safety and efficacy of combined percutaneous left atrial appendage occlusion (LAAO) and catheter ablation (CA) to LAAO alone are limited.

Methods: Patients from a large US hospital system undergoing combined LAAO and left-atrial CA from 8/2020 to 2/2024 were retrospectively analyzed and compared to a control group undergoing LAAO alone. Controls were identified using a 1:2 propensity score match based on LAAO device type (Watchman FLX vs.

Retinal perivascular macrophages regulate immune cell infiltration during neuroinflammation in mouse models of ocular disease.

The blood-retina barrier (BRB), which is disrupted in diabetic retinopathy (DR) and uveitis, is an important anatomical characteristic of the retina, regulating nutrient, waste, water, protein, and immune cell flux. The BRB is composed of endothelial cell tight junctions, pericytes, astrocyte end feet, a collagen basement membrane, and perivascular macrophages. Despite the importance of the BRB, retinal perivascular macrophage function remains unknown.

NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development.

While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generated retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing (scRNA-Seq) across the developmental window encompassing photoreceptor specification, emergence, and maturation.

Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

Background: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear.

Methods: Adult (n=67 221; mean age, 72.4±12.

Patient Outcomes by Ventricular Systolic and Diastolic Function.

Background: Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes.

Methods And Results: Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD.

Association of pre-left ventricular assist device defibrillator shocks for ventricular arrhythmia with clinical outcomes after left ventricular assist device implantation.

Background: Implantable cardioverter-defibrillation (ICD) shocks after left ventricular assist device therapy (LVAD) are associated with adverse clinical outcomes. Little is known about the association of pre-LVAD ICD shocks on post-LVAD clinical outcomes and whether LVAD therapy affects the prevalence of ICD shocks.

Objectives: The purpose of this study was to determine whether pre-LVAD ICD shocks are associated with adverse clinical outcomes post-LVAD and to compare the prevalence of ICD shocks before and after LVAD therapy.

Outcomes of in-office versus operating room insertion of tympanostomy tubes in children.

Objective: Tympanostomy tube insertion in children is commonly performed under general anesthesia, but there has been increasing interest in office-based alternatives. Although initial research comparing in-office versus operating room (OR) insertion of tubes looks promising, there are scant data available on long-term outcomes. The objective of this study is to compare long-term outcomes of tympanostomy tubes placed in-office versus the OR, with emphasis on the duration of tube function.

NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration.

Background: Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1 mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes.

Cardiovascular Hospitalizations and Resource Use Following Atrial Fibrillation Ablation.

Background Over the next few years, atrial fibrillation (AF)-related morbidity and costs will increase significantly. Thus, it is prudent to examine the impact of AF treatment on health care resource use. This study examined the impact of AF ablation on hospitalization, length of stay, and resource use for patients undergoing AF ablation in a multihospital system.

GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS.

Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process. In this study, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor.

Multimodal single-cell analysis of nonrandom heteroplasmy distribution in human retinal mitochondrial disease.

Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multisystem disease. The wide range of manifestations observed in patients with mitochondrial disease results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. However, the landscape of heteroplasmy across cell types within tissues and its influence on phenotype expression in affected patients remains largely unexplored.

Propensity of Patient-Derived iPSCs for Retinal Differentiation: Implications for Autologous Cell Replacement.

Prior to use, newly generated induced pluripotent stem cells (iPSC) should be thoroughly validated. While excellent validation and release testing assays designed to evaluate potency, genetic integrity, and sterility exist, they do not have the ability to predict cell type-specific differentiation capacity. Selection of iPSC lines that have limited capacity to produce high-quality transplantable cells, places significant strain on valuable clinical manufacturing resources.

Relative Contribution of Atrial Fibrillation to Outcomes of Patients With Cardiomyopathy Based on Severity of Left Ventricular Dysfunction.

In patients with left ventricular (LV) dysfunction, the risk of death or heart failure hospitalizations (HFHs) increases with worsening ejection fraction (EF). Whether the relative contribution of atrial fibrillation (AF) to outcomes is more pronounced in patients with worse EF is not confirmed. The present study aimed to investigate the relative influence of AF on the outcome of cardiomyopathy patients by severity of LV dysfunction.

Ventricular conduction abnormality in patients with mild to moderate cardiomyopathy.

Background: In mild-to-moderate cardiomyopathy, cardiac resynchronization therapy (CRT) is indicated in patients with high burden of right ventricular pacing but not in those with intrinsic ventricular conduction abnormalities.

Hypothesis: We hypothesized that CRT positively impacts outcomes of patients with intrinsic ventricular conduction delay and left ventricular ejection fraction (LVEF) of 36%-50%.

Methods: Of 18 003 patients with LVEF ≤ 50%, 5966 (33%) patients had mild-to-moderate cardiomyopathy, of whom 1741 (29%) have a QRS duration ≥120 ms.

Automating iPSC generation to enable autologous photoreceptor cell replacement therapy.

Background: Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation.

Methods: In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs.

Impact of a dedicated center for atrial fibrillation on resource utilization and costs.

Background: Atrial fibrillation (AF) affects millions of Americans each year and can lead to high levels of resource utilization through emergency department (ED) visits and inpatient stays.

Hypothesis: We hypothesized that referral of patients to a dedicated Center for AF from the ED would reduce costs of care.

Methods: The University of Pittsburgh Center for AF serves as a rapid referral center for patients with AF to avoid unnecessary inpatient admissions and provide specialized care.

Retinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.

Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs.