Utility of Novel Cardiorenal Biomarkers in the Prediction and Early Detection of Congestive Kidney Injury Following Cardiac Surgery

Acute Kidney Injury (AKI) in the context of right ventricular failure (RVF) is thought to be largely congestive in nature. This study assessed the utility of biomarkers high sensitivity cardiac troponin T (hs-cTnT), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for prediction and early detection of congestive AKI (c-AKI) following cardiac surgery. This prospective nested case-control study recruited 350 consecutive patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. Cases were patients who developed (1) AKI (2) new or worsening RVF, or (3) c-AKI. Controls were patients free of these complications. Biomarker levels were measured at baseline after anesthesia induction and immediately postoperatively. Patients with c-AKI had increased mean duration of mechanical ventilation and length of stay in hospital and in the intensive care unit (p < 0.01). For prediction of c-AKI, baseline NT-proBNP yielded an area under the curve (AUC) of 0.74 (95% CI, 0.60⁻0.89). For early detection of c-AKI, postoperative NT-proBNP yielded an AUC of 0.78 (0.66⁻0.91), postoperative hs-cTnT yielded an AUC of 0.75 (0.58⁻0.92), and ∆hs-cTnT yielded an AUC of 0.80 (0.64⁻0.96). The addition of baseline creatinine to ∆hs-cTnT improved the AUC to 0.87 (0.76⁻0.99), and addition of diabetes improved the AUC to 0.93 (0.88⁻0.99). Δhs-cTnT alone, or in combination with baseline creatinine or diabetes, detects c-AKI with high accuracy following cardiac surgery

Real‐world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real‐world Evidence Working Group

Abstract This manuscript on real‐world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real‐World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real‐world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community

Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.[Display omitted]•A systematic inventory of HNSCC-associated proteins, phosphosites, and pathways•Three multi-omic subtypes linked to targeted treatment approaches and immunotherapy•Widespread deletion of immune modulatory genes accounts for loss of immunogenicity•Two modes of EGFR activation inform response to anti-EGFR monoclonal antibodiesHuang et al. report a proteogenomic study on 108 HPV-negative head and neck squamous cell carcinomas (HNSCCs). In addition to creating a comprehensive resource for pathogenic insights, multi-omic analysis identifies therapeutic hypotheses that may inform more precise approaches to treatment