Internal Medicine Commons^™

Exome Sequencing Identifies Gene Variants And Networks Associated With Extreme Respiratory Outcomes Following Preterm Birth, Aaron Hamvas, Rui Feng, Yingtao Bi, Fan Wang, Soumyaroop Bhattacharya, Jared Mereness, Madhurima Kaushal, C Michael Cotten, Philip L Ballard, Thomas J Mariani

Journal Articles

BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.

RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for …

Effect Of Aspirin On All-Cause Mortality In The Healthy Elderly, John J Mcneil, Mark R Nelson, Robyn L Woods, Jessica E Lockery, Rory Wolfe, Christopher M Reid, Brenda Kirpach, Raj C Shah, Diane G Ives, Elsdon Storey, Joanne Ryan, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Barbara Radziszewska, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics …

Effect Of Aspirin On Cardiovascular Events And Bleeding In The Healthy Elderly, John J Mcneil, Rory Wolfe, Robyn L Woods, Andrew M Tonkin, Geoffrey A Donnan, Mark R Nelson, Christopher M Reid, Jessica E Lockery, Brenda Kirpach, Elsdon Storey, Raj C Shah, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Michael Jelinek, Mobin Malik, Charles B Eaton, Donna Brauer, Geoff Cloud, Erica M Wood, Suzanne E Mahady, Suzanne Satterfield, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk.

METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a …

Effect Of Aspirin On Disability-Free Survival In The Healthy Elderly, John J Mcneil, Robyn L Woods, Mark R Nelson, Christopher M Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey, Raj C Shah, Jessica E Lockery, Andrew M Tonkin, Anne B Newman, Jeff D Williamson, Karen L Margolis, Michael E Ernst, Walter P Abhayaratna, Nigel Stocks, Sharyn M Fitzgerald, Suzanne G Orchard, Ruth E Trevaks, Lawrence J Beilin, Geoffrey A Donnan, Peter Gibbs, Colin I Johnston, Joanne Ryan, Barbara Radziszewska, Richard Grimm, Anne M Murray

Journal Articles

BACKGROUND: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end …

A Systematic Review Of The Efficacy And Safety Of Fecal Microbiota Transplant For Clostridium Difficile Infection In Immunocompromised Patients, Oluwaseun Shogbesan, Dilli Ram Poudel, Samjeris Victor, Asad Jehangir, Opeyemi Fadahunsi, Gbenga Shogbesan, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent

Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.

Results: Forty-four studies were included, none of which were randomized designs. A total …

Precision Oncology Decision Support: Current Approaches And Strategies For The Future, Katherine C Kurnit, Ecaterina E Ileana Dumbrava, Beate Litzenburger, Yekaterina B Khotskaya, Amber M Johnson, Timothy A Yap, Jordi Rodon, Jia Zeng, Md Abu Shufean, Ann M Bailey, Nora S Sánchez, Vijaykumar Holla, John Mendelsohn, Kenna Mills Shaw, Elmer V Bernstam, Gordon B Mills, Funda Meric-Bernstam

Journal Articles

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and …

Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen Rennard, Byron Thomashow, Barbara P. Yawn

Preventive Medicine and Environmental Health Faculty Publications

Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC)11 60%–80% predicted) who may also benefit from diagnosis and treatment.

Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were …

Exacerbation Recovery Patterns In Newly Diagnosed Or Maintenance Treatment-Naïve Patients With Copd: Secondary Analyses Of Ticari 1 Trial Data, David M. Mannino, Emmanuelle M. Clerisme-Beaty, Joanne Franceschina, Naitee Ting, Nancy K. Leidy

Preventive Medicine and Environmental Health Faculty Publications

Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI).

Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care …

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Journal Articles

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …

Delayed Sternal Closure Does Not Reduce Complications Associated With Coagulopathy And Right Ventricular Failure After Left Ventricular Assist Device Implantation, Roh Yanagida, Navin Rajagopalan, Daniel L. Davenport, Thomas A. Tribble, Mark A. Bradley, Charles W. Hoopes

Internal Medicine Faculty Publications

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Vitamin E Status Is Inversely Associated With Risk Of Incident Tuberculosis Disease Among Household Contacts, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray

Journal Articles

BACKGROUND: Few studies have previously assessed how pre-existing vitamin E status is associated with risk of tuberculosis (TB) disease progression.

OBJECTIVE: We evaluated the association between baseline plasma concentrations of 3 vitamin E isomers (α-tocopherol, γ-tocopherol, and δ-tocopherol) and TB disease risk.

METHODS: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima, Peru. We defined cases as HHCs who developed active TB disease ≥15 d after the diagnosis of the index patient, and we matched each case to 4 control cases who did not develop active TB based on …