Diseases Commons^™

The Development Of Azd7624 For Prevention Of Exacerbations In Copd: A Randomized Controlled Trial, Naimish R. Patel, Danen M. Cunoosamy, Malin Fagerås, Ziad Taib, Sara Asimus, Tove Hegelund-Myrbäck, Sofia Lundin, Katerina Pardali, Nisha Kurian, Eva Ersdal, Cecilia Kristensson, Katarina Korsback, Robert Palmér, Mary N. Brown, Steven Greenaway, Leonard Siew, Graham W. Clarke, Stephen I. Rennard, Barry J. Make, Robert A. Wise, Paul Jansson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.

OBJECTIVES: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD. The principal hypothesis was that decreasing lung inflammation via inhibition of p38α would reduce exacerbations and improve quality of life for COPD patients at high risk for acute exacerbations.

METHODS: The p38 isoform most relevant to lung inflammation was assessed …

Influence Of Dietary Salt Knowledge, Perceptions, And Beliefs On Consumption Choices After Stroke In Uganda, Martin N. Kaddumukasa, Elly Katabira, Martha Sajatovic, Svetlana Pundik, Mark Kaddumukasa, Larry B. Goldstein

Neurology Faculty Publications

Background

Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices.

Purpose

Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda.

Methods

Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships …

Serum Microrna-27b As A Screening Biomarker For Left Ventricular Hypertrophy, Yan Wang, Shuyan Chen, Yanhong Gao, Song Zhang

The Texas Heart Institute Journal

MicroRNA-27b (miR-27b) is frequently upregulated in pressure-overloaded hypertrophic hearts. The clinical implications of aberrant circulating miR-27b in the diagnosis and management of left ventricular hypertrophy warrant study. We investigated whether serum miR-27b is a biomarker for left ventricular hypertrophy (LVH).

We used stem-loop reverse-transcription quantitative polymerase chain reaction techniques to analyze serum miR-27b levels in 200 hypertensive patients with LVH, 100 hypertensive patients without LVH, and 100 healthy volunteers. We found that serum miR-27b levels were significantly higher in the hypertensive patients with LVH than in the hypertensive patients without LVH and in the healthy volunteers. Upon receiver operating characteristic …

Multimodal Imaging Of Anomalous Left Coronary Artery From The Pulmonary Artery In A 75-Year-Old Woman, Margaret M Fuchs, Rachel J Le, Michael W Cullen, Joseph J Maleszewski, Naser M Ammash

The Texas Heart Institute Journal

Anomalous origin of the left coronary artery from the pulmonary artery is rare and typically results in mitral regurgitation, ventricular arrhythmias, heart failure, and sudden death. The condition most often manifests itself in early childhood, but some individuals are diagnosed much later. We describe the case of a 75-year-old woman with heart failure in whom stepwise multimodal imaging revealed anomalous origin of the left coronary artery from the pulmonary artery.

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Cerebral Amyloid Angiopathy In Down Syndrome And Sporadic And Autosomal-Dominant Alzheimer's Disease, María Carmona-Iragui, Mircea Balasa, Bessy Benejam, Daniel Alcolea, Susana Fernández, Laura Videla, Isabel Sala, María Belén Sánchez-Saudinós, Estrella Morenas-Rodriguez, Roser Ribosa-Nogué, Ignacio Illán-Gala, Sofía Gonzalez-Ortiz, Jordi Clarimón, Frederick A. Schmitt, David K. Powell, Beatriz Bosch, Albert Lladó, Michael S. Rafii, Elizabeth Head, José Luis Molinuevo, Rafael Blesa, Sebastián Videla, Alberto Lleó, Raquel Sánchez-Valle, Juan Fortea

Sanders-Brown Center on Aging Faculty Publications

Introduction—We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods—Neuroimaging features of CAA, APOE, and cerebrospinal fluid-Aβ40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results—CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. …

Cruciferous And Allium Vegetable Intakes Are Inversely Associated With 15‐Year Atherosclerotic Vascular Disease Deaths In Older Adult Women, Lauren Blekkenhorst, Catherine P. Bondonno, Joshua Lewis, Amanda Devine, Kun Zhu, Wai Lim, Richard Woodman, Lawrence Beilin, Richard Prince, Jonathan M. Hodgson

Research outputs 2014 to 2021

Background

Higher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality.

Methods and Results

The cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were …

Randomized Phase Ii Study Comparing Prophylactic Cranial Irradiation Alone To Prophylactic Cranial Irradiation And Consolidative Extracranial Irradiation For Extensive-Disease Small Cell Lung Cancer (Ed Sclc): Nrg Oncology Rtog 0937, Elizabeth M. Gore, Chen Hu, Alexander Y. Sun, Daniel F. Grimm, Suresh S. Ramalingam, Neal E. Dunlap, Kristin A. Higgins, Maria Werner-Wasik, Aaron M. Allen, Puneeth Iyengar, Gregory M. M. Videtic, Russell K. Hales, Ronald C. Mcgarry, James J. Urbanic, Anthony T. Pu, Candice A. Johnstone, Volker W. Stieber, Rebecca Paulus, Jeffrey D. Bradley

Radiation Medicine Faculty Publications

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC.

Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age < 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required.

Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study …

Left Circumflex Coronary Artery As The Culprit Vessel In St-Segment-Elevation Myocardial Infarction, Diab Ghanim, Fabio Kusniec, Wadi Kinany, Dahud Qarawani, David Meerkin, Khaled Taha, Offer Amir, Shemy Carasso

The Texas Heart Institute Journal

The prevalence of the left circumflex coronary artery (LCx) as the culprit vessel in ST-segment-elevation myocardial infarction (STEMI) is reportedly lowest among that of the 3 main epicardial arteries, and has not been described for non-STEMI (NSTEMI) and stable angina pectoris. We sought to define the distribution of culprit arteries in these clinical presentations and suggest mechanisms for the differences.

We reviewed 189 coronary angiograms of patients with STEMI, 203 with NSTEMI, and 548 with stable angina (n=940), and compared distributions of stenotic and culprit coronary arteries (lesions prompting intervention).

Obstructive coronary lesions (≥50% narrowing) were more prevalent in the …

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Optical Coherence Tomographic Evaluation Of Hyperacute Bivalirudin-Induced Coronary Stent Thrombosis, Jorge L Peñalver, Wassim Shatila, Emerson Perin

The Texas Heart Institute Journal

Thrombus formation after stent deployment has been linked to the use of heparin and of antithrombotic agents, such as bivalirudin, during percutaneous coronary intervention. Fluoroscopy has been used to identify stent thrombosis, typically after patients become symptomatic. We describe our use of optical coherence tomography to diagnose and evaluate intraprocedural stent thrombosis in a 68-year-old man who was given bivalirudin just before a percutaneous coronary procedure. This imaging method enabled immediate therapeutic intervention.

Higher Mineralized Bone Volume Is Associated With A Lower Plain X-Ray Vascular Calcification Score In Hemodialysis Patients, Teresa Adragao, Anibal Ferreira, Joao M. Frazao, Ana Luisa Papoila, Iola Pinto, Marie-Claude Monier-Faugere, Hartmut H. Malluche

Internal Medicine Faculty Publications

Background and objectives

In dialysis patients, there is an increasing evidence that altered bone metabolism is associated with cardiovascular calcifications. The main objective of this study was to analyse, in hemodialysis patients, the relationships between bone turnover, mineralization and volume, evaluated in bone biopsies, with a plain X-ray vascular calcification score.

Design, setting, participants and measurements

In a cross-sectional study, bone biopsies and evaluation of vascular calcifications were performed in fifty hemodialysis patients. Cancellous bone volume, mineralized bone volume, osteoid volume, activation frequency, bone formation rate/bone surface, osteoid thickness and mineralization lag time were determined by histomorphometry. Vascular calcifications were …

Evaluation Of Chest Pain After Implantable Cardioverter-Defibrillator Placement, Amir Gahremanpour, Mohammad Saeed, Yochai Birnbaum

The Texas Heart Institute Journal

No abstract provided.

White Blood Cell Subtypes Are Associated With A Greater Long-Term Risk Of Death After Acute Myocardial Infarction, Arthur Shiyovich, Harel Gilutz, Ygal Plakht

The Texas Heart Institute Journal

We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction.

In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total …

Seroprevalence Of Poliovirus Antibodies In The Kansas City Metropolitan Area, 2012-2013., Gregory S. Wallace, Barbara A. Pahud, William C. Weldon, Aaron T. Curns, M Steven Oberste, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, …

White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith

Biomedical Engineering Faculty Publications

Objective: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Methods: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluidattenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slicebased techniques. Results: dWMHs but not …

Long-Term Excess Risk Of Stroke In People With Type 2 Diabetes In Sweden According To Blood Pressure Level: A Population-Based Case-Control Study., C Hedén Ståhl, M Lind, A-M Svensson, M Kosiborod, S Gudbjörnsdottir, A Pivodic, Mark A. Clements, A Rosengren

Manuscripts, Articles, Book Chapters and Other Papers

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden.

METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals …

Prolonged Sinus Pauses Upon Termination Of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic And Electroanatomic Findings, Zhengyu Bao, Hongwu Chen, Bing Yang, Michael Shehata, Weizhu Ju, Fengxiang Zhang, Gang Yang, Kai Gu, Mingfang Li, Kejiang Cao, Xunzhang Wang, Minglong Chen

The Texas Heart Institute Journal

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients.

Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs …

Clinical Risk Factors For Infective Endocarditis In Staphylococcus Aureus Bacteremia, Vincent Bryan D Salvador, Bikash Chapagain, Astha Joshi, Debra J Brennessel

The Texas Heart Institute Journal

Crucial to the management of staphylococcal bacteremia is an accurate evaluation of associated endocarditis, which has both therapeutic and prognostic implications. Because the clinical presentation of endocarditis can be nonspecific, the judicious use of echocardiography is important in distinguishing patients at high risk of developing endocarditis. In the presence of high-risk clinical features, an early transesophageal echocardiogram is warranted without prior transthoracic echocardiography.

The purpose of this study was to investigate the clinical risk factors for staphylococcal infective endocarditis that might warrant earlier transesophageal echocardiography and to describe the incidence of endocarditis in cases of methicillin-resistant and methicillin-sensitive Staphylococcus aureus …

Percutaneous Valvuloplasty For Bioprosthetic Tricuspid Valve Stenosis, Gaurav Rana, Rohit Malhotra, Anjali Sharma, Nikolaos Kakouros

The Texas Heart Institute Journal

Percutaneous transcatheter tricuspid balloon valvuloplasty (PTTBV) is an accepted treatment option for symptomatic severe native tricuspid valve stenosis, although surgical tricuspid valve replacement remains the treatment of choice. There have been few reports of successful PTTBV for bioprosthetic tricuspid valve stenosis. We present case reports of 3 patients from our hospital experience. Two of the 3 cases were successful, with lasting clinical improvement, whereas the 3rd patient failed to show a reduction in valve gradient. We describe the standard technique used for PTTBV. We present results from a literature review that identified 16 previously reported cases of PTTBV for bioprosthetic …

Cancer Antigen 125 Is Associated With Length Of Stay In Patients With Acute Heart Failure, Hakki Kaya, Recep Kurt, Osman Beton, Ali Zorlu, Hasan Yucel, Hakan Gunes, Didem Oguz, Mehmet Birhan Yilmaz

The Texas Heart Institute Journal

Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay ≤4 days and those with lengths of stay >4 days. Patients with longer lengths of stay had …

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Behavioral Science Faculty Publications

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Reliability And Validity Of The Hd-Pro-Triadtm, A Health-Related Quality Of Life Measure Designed To Assess The Symptom Triad Of Huntington's Disease., Nicholas R Boileau, Julie C Stout, Janes S Paulsen, David Cella, Michael K Mccormack, Martha A Nance, Samuel Frank, Jin-Shei Lai, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Huntington's disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable.

OBJECTIVES: The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD.

METHODS: Four-hundred and eighty-two individuals with HD (n = 192 prodromal, n = 193 early, and n …

Delirium Update For Postacute Care And Long-Term Care Settings: A Narrative Review., Martin M Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Advances have been made in our understanding of the neuropathogenesis, recognition, and strategies for reducing the incidence of delirium in acute-care settings. However, relatively little attention has been given to delirium in elderly patients in the postacute care (PAC) and long-term care (LTC) settings. The present article reviews the most relevant current research pertaining to this population. Hospital patients with delirium are often discharged to PAC settings. Delirium that develops in the LTC setting is often more insidious and subtle in presentation. Despite incorporating systematic screening tools for delirium in PAC and LTC settings, delirium prevention strategies have not yet …

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …