Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Technical Performance Evaluation of Olink Proximity Extension Assay for Blood-Based Biomarker Discovery in Longitudinal Studies of Alzheimer's Disease.

The core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers; amyloid-ß (Aß), total tau (t-tau), and phosphorylated tau (p-tau181), are strong indicators of the presence of AD pathology, but do not correlate well with disease progression, and can be difficult to implement in longitudinal studies where repeat biofluid sampling is required. As a result, blood-based biomarkers are increasingly being sought as alternatives. In this study, we aimed to evaluate a promising blood biomarker discovery technology, Olink Proximity Extension Assays for technical reproducibility characteristics in order to highlight the advantages and disadvantages of using this technology in biomarker discovery in AD. We evaluated the performance of five Olink Proteomic multiplex proximity extension assays (PEA) in plasma samples. Three technical control samples included on each plate allowed calculation of technical variability. Biotemporal stability was measured in three sequential annual samples from 54 individuals with and without AD. Coefficients of variation (CVs), analysis of variance (ANOVA), and variance component analyses were used to quantify technical and individual variation over time. We show that overall, Olink assays are technically robust, with the largest experimental variation stemming from biological differences between individuals for most analytes. As a powerful illustration of one of the potential pitfalls of using a multi-plexed technology for discovery, we performed power calculations using the baseline samples to demonstrate the size of study required to overcome the need for multiple test correction with this technology. We show that the power of moderate effect size proteins was strongly reduced, and as a result investigators should strongly consider pooling resources to perform larger studies using this multiplexed technique where possible.