Medicine and Health Sciences Commons^™

Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in …

Oral Apolipoprotein A-I Mimetic D-4f Lowers Hdl-Inflammatory Index In High-Risk Patients: A First-In-Human Multiple-Dose, Randomized Controlled Trial., Richard L. Dunbar, Rajesh Movva, Leanne T. Bloedon, Danielle Duffy, Robert B. Norris, Mohamad Navab, Alan M. Fogelman, Daniel J. Rader

Department of Medicine Faculty Papers

A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated. Mean ± SD plasma D-4F area under the curve (AUC, 0-8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± …

Impact Of Superstorm Sandy On Medicare Patients' Utilization Of Hospitals And Emergency Departments., Benoit Stryckman, Lauren Walsh, Brendan G. Carr, Nathaniel Hupert, Nicole Lurie

Department of Emergency Medicine Faculty Papers

INTRODUCTION: National health security requires that healthcare facilities be prepared to provide rapid, effective emergency and trauma care to all patients affected by a catastrophic event. We sought to quantify changes in healthcare utilization patterns for an at-risk Medicare population before, during, and after Superstorm Sandy's 2012 landfall in New Jersey (NJ).

METHODS: This study is a retrospective cohort study of Medicare beneficiaries impacted by Superstorm Sandy. We compared hospital emergency department (ED) and healthcare facility inpatient utilization in the weeks before and after Superstorm Sandy landfall using a 20% random sample of Medicare fee-for-service beneficiaries continuously enrolled in 2011 …

Efficacy And Safety Of Spironolactone In Acute Heart Failure: The Athena-Hf Randomized Clinical Trial., Javed Butler, Kevin J. Anstrom, G. Michael Felker, Michael M. Givertz, Andreas P Kalogeropoulos, Marvin A. Konstam, Douglas L. Mann, Kenneth B. Margulies, Steven E Mcnulty, Robert J. Mentz, Margaret M. Redfield, W.H. Wilson Tang, David J. Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald

Department of Medicine Faculty Papers

Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF.

Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone.

Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had …

Discordance In Investigator-Reported And Adjudicated Sudden Death In Tiospir., Robert A. Wise, Peter R. Kowey, George Austen, Achim Mueller, Norbert Metzdorf, Andy Fowler, Lorcan P Mcgarvey

Department of Medicine Faculty Papers

Accurate and consistent determination of cause of death is challenging in chronic obstructive pulmonary disease (COPD) patients. TIOSPIR (N=17 135) compared the safety and efficacy of tiotropium Respimat 5/2.5 µg with HandiHaler 18 µg in COPD patients. All-cause mortality was a primary end-point. A mortality adjudication committee (MAC) assessed all deaths. We aimed to investigate causes of discordance in investigator-reported and MAC-adjudicated causes of death and their impact on results, especially cardiac and sudden death. The MAC provided independent, blinded assessment of investigator-reported deaths (n=1302) and assigned underlying cause of death. Discordance between causes of death was assessed descriptively (shift …