Primary Graft Dysfunction after Heart Transplantation: Current Evidence and Implications for Clinical Practice.

Purpose Of Review: This review summarizes the current literature on primary graft dysfunction highlighting the current definition, reviewing epidemiology, and describing donor, recipient, and perioperative risk factors in the contemporary era.

Recent Findings: PGD, in its most severe form, complicates 8% of heart transplants and portends a 1-year mortality of close to 40%. PGD is multifactorial and heterogeneous with contributions from donor and recipient risk as well as organ recovery and preservation modalities.

Leveraging Systematic Functional Analysis to Benchmark an Framework Distinguishes Driver from Passenger MEK Mutants in Cancer.

Despite significant advances in cancer precision medicine, a significant hurdle to its broader adoption remains the multitude of variants of unknown significance identified by clinical tumor sequencing and the lack of biologically validated methods to distinguish between functional and benign variants. Here we used functional data on and mutations generated in real-time within a co-clinical trial framework to benchmark the predictive value of a three-part methodology. Our computational approach to variant classification incorporated hotspot analysis, three-dimensional molecular dynamics simulation, and sequence paralogy.

Efficacy and Determinants of Response to HER Kinase Inhibition in -Mutant Metastatic Breast Cancer.

mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with -mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade.

Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis.

Altered expression of XPO1, the main nuclear export receptor in eukaryotic cells, has been observed in cancer, and XPO1 has been a focus of anticancer drug development. However, mechanistic evidence for cancer-specific alterations in XPO1 function is lacking. Here, genomic analysis of 42,793 cancers identified recurrent and previously unrecognized mutational hotspots in XPO1 mutations exhibited striking lineage specificity, with enrichment in a variety of B-cell malignancies, and introduction of single amino acid substitutions in XPO1 initiated clonal, B-cell malignancy .