Whole-body galactose oxidation as a robust functional assay to assess the efficacy of gene-based therapies in a mouse model of Galactosemia.

Despite the implementation of lifesaving newborn screening programs and a galactose-restricted diet, many patients with classic galactosemia develop long-term debilitating neurological deficits and primary ovarian insufficiency. Previously, we showed that the administration of human mRNA predominantly expressed in the gene-trapped mouse liver augmented the expression of hepatic GALT activity, which decreased not only galactose-1 phosphate (gal-1P) in the liver but also peripheral tissues. Since each peripheral tissue requires distinct methods to examine the biomarker and/or GALT effect, this highlights the necessity for alternative strategies to evaluate the overall impact of therapies.

Increased severe primary graft dysfunction in left ventricular assist device patients following united network for organ sharing allocation changes.

Introduction: In 2018, the United Network for Organ Sharing (UNOS) implemented a new heart allocation system which prioritized patients on temporary support devices and left-ventricular assist device (LVAD) patients with complications. These changes have the potential to impact outcomes for patients bridged to transplant with an LVAD.

Methods: We performed a retrospective study of 168 adult heart transplant recipients at our center between 2016 and 2020 evaluating post-transplant outcomes before and after UNOS allocation changes.

Improvements in Extracorporeal Membrane Oxygenation for Primary Graft Failure After Heart Transplant.

Background: Severe primary graft failure is a life-threatening complication of heart transplantation that may require venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Surgical practices and management strategies regarding VA-ECMO vary between and within centers.

Methods: We performed a single-center retrospective cohort study on adult patients who received VA-ECMO for primary graft failure between 2013 and 2020.

Worsening Renal Function in Cardiac Mechanical Support.

Background: Venous congestion in heart failure (HF) may lead to worsening renal failure (WRF). We hypothesised that WRF in patients hospitalised for left ventricular assist device (LVAD) implantation is associated with increased 1-year mortality. There is limited data regarding WRF in HF patients with mechanical support.

The Impact of Pazopanib on the Cardiovascular System.

Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown.

Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model.

Background: In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.

Objective: Define the in vivo role of pazopanib in the development of cardiotoxicity.

The role of βII spectrin in cardiac health and disease.

Spectrins are large, flexible proteins comprised of α-β dimers that are connected head-to-head to form the canonical heterotetrameric spectrin structure. Spectrins were initially believed to be exclusively found in human erythrocytic membrane and are highly conserved among different species. βII spectrin, the most common isoform of non-erythrocytic spectrin, is found in all nucleated cells and forms larger macromolecular complexes with ankyrins and actins.