Diseases Commons^™

Anomalous Origin Of The Left Coronary Artery From The Pulmonary Artery: A Surgical Certainty, Ayesha Butt, Muhammad Muneer Amanullah, Mehnaz Atiq Ahmed, Asif Hasan, Waris Ahmad

Medical College Documents

This study aims to assess the clinical presentation and the outcomes of a surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). A retrospective review was carried out on the charts of six patients admitted for ALCAPA surgery at Aga Khan University Hospital, Karachi from March 2017 to May 2018.Dyspnoea, palpitation, poor feeding, fatiguability, pallor and a murmur of mitral regurgitation were the main presenting features. The pre-operative median left ventricular ejection fraction (LVEF) was 64%. Coronary reimplantation was performed in all the patients with a mitral valve repair being done in only …

Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet

Q2S Enhancing Pedagogy

The syllabus has newly developed learning objectives that will prepare students entering the field of clinical exercise physiology. This course will cover the etiology and pathophysiology of many chronic diseases that plague the population. Assessments of chronic diseases include but are not limited to understanding symptomology will also be covered. Due to the limitations in time the most prevalent chronic disease will be covered and students will have to present on a disease that was not presented in class. The practical application portion of this course will take place during a lab section. Here students will have the opportunity to …

Hemodynamic And Clinical Effects Of Selexipag In Children With Pulmonary Hypertension, Abraham Rothman, Gabriel Cruz, William N. Evans, Humberto Restrepo

School of Medicine Faculty Research

Selexipag is an oral prostacyclin receptor agonist; it was recently approved for use in adults with pulmonary arterial hypertension. The safety and efficacy of selexipag has not yet been determined in the pediatric population. We describe short-term hemodynamic and clinical data with selexipag therapy in four pediatric patients with pulmonary hypertension. We reviewed clinical, echocardiographic, and hemodynamic data. One patient was transitioned from subcutaneous treprostinil to selexipag, and in three patients, selexipag was added as a third agent. Drug dosing was attained empirically based on patient body size. A follow-up catheterization was performed 12–18 months after initiation of selexipag therapy. …

A Real-World Analysis Of Patient Characteristics And Predictors Of Hospitalization Among Us Medicare Beneficiaries With Respiratory Syncytial Virus Infection, Veronique Wyffels, Furaha Kariburyo, Sandra Gavart, Roman Fleischhackl, Huseyin Yuce

Publications and Research

Introduction: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. Methods: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identified using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was defined as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the base-line period. …

Mathematical Modelling Of The Tuberculosis Epidemiology, Ally Yeketi Ayinla

Student Works (2020-2029)

This project analyses the tuberculosis (TB) epidemic mathematically using compartmental modelling approach. Three models are presented to discuss drug susceptible and multi-drug resistant TB. The first model presented has 4 compartments; susceptible, exposed, infectious and recovered. The relevance of the exposed class in managing TB is analysed and found to be useful in delaying the eventual onset of the infection. Compared to previous researches, our results significantly show that when efforts are made such that no infected individual bypasses the exposed class and progresses directly to the infectious, the TB epidemic is successfully combatted. Also, the model is used to …

The Elevated Systemic Cytokine Levels In Hiv Patients Are Not Associated With An Elevated Pulmonary Cytokine Environment., Rafael Fernandez-Botran, Andrea Reyes-Vega, Yasmany García, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Anupama Raghuram, Paula Peyrani, Stephen P. Furmanek, Mahder A. Tella, Jeffrey D. Ritzenthaler, Jesse Roman, Julio A. Ramirez

Faculty and Staff Scholarship

Background

HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels.

Methods

This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid …

Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe

Faculty, Staff and Students Publications

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca²⁺-activated and voltage-dependent K⁺ (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).

Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Methods: Losartan’s antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for …

How Deep Is Too Deep?, Dietrich Schlueter Md, Asma Jamil Md, Ibrahim Talab, Samia Faiz, Scott Kubomoto Md

Internal Medicine

No abstract provided.

Always Remember To Floss... Or Else, Arunmozhi (Sankavi) Aravagiri Md, Muhammad Zain Md, Rajesh Gulati Md

Internal Medicine

No abstract provided.

Older Adults Hospitalized For Pneumonia In The United States: Incidence, Epidemiology, And Outcomes., Forest W. Arnold, Andrea Reyes-Vega, Vidyulata Salunkhe, Stephen P. Furmanek, Christian Furman, Laura Morton, Anna Johan Faul, Pam Yankeelov, Julio A. Ramirez

Faculty and Staff Scholarship

OBJECTIVES: To define the current incidence, epidemiology, and mortality of older adult patients hospitalized with community-acquired pneumonia (CAP) in Louisville, KY and thus estimate the burden of CAP in the older adult population of the United States. To define risk factors associated with early and late outcomes. DESIGN: This was a secondary analysis of older adults (aged ≥65 years) from the University of Louisville Pneumonia Study, a prospective population-based cohort study of all hospitalized adults with CAP between June 1, 2014, and May 31, 2016. SETTING: The study took place in all nine acute care hospitals for adults in Louisville, …

Literature Review Of Covid-19 Biochemistry, Alexandra Allen

2020 Symposium Posters

SARS-CoV-2 is the virus responsible for the current pandemic. SARS-CoV-2 is a betacoronavirus with a genome that is 79.5% identical to SARS-CoV. The virus enters T lymphocytes using its spike protein with the human angiotension-converting enzyme 2 as its receptor. SARS-CoV-2 was found to have a unique peptide sequence that could contribute to the proteolytic cleavage of the spike protein, therefore potentially impacting host range and transmissibility. COVID-19 is diagnosed through a nasal swab SARS-CoV-2 RT-PCR assay and the most common symptoms appear to be fever, cough, and fatigue. The median amount of time an individual will be contagious with …

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …

Co-Morbidity Patterns Identified Using Latent Class Analysis Of Medications Predict All-Cause Mortality Independent Of Other Known Risk Factors: The Copdgene® Study, Yisha Li, Margaret Ragland, Erin Austin, Kendra Young, Katherine Pratte, John E. Hokanson, Terri H Beaty, Elizabeth A. Regan, Stephen I. Rennard, Christina Wern, Michael R. Jacobs, Ruth Tal-Singer, Barry J. Make, Gregory L. Kinney, Copdgene Investigators

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life.

MATERIALS AND METHODS: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic …

Progressive Dyspnea After Use Of Electronic Vaping, Taylor Studsrud, Morgan Zegers, Gary Cook, Narrani Kanapathippillai, Hilton Alemar-Hernandez

West Florida Division GME Research Day 2020

No abstract provided.

Blood Eosinophil Counts In Clinical Trials For Chronic Obstructive Pulmonary Disease, Dave Singh, Mona Bafadhel, Christopher E. Brightling, Frank C. Sciurba, Jeffrey L. Curtis, Fernando J. Martinez, Cara B. Pasquale, Debora D. Merrill, Norbert Metzdorf, Stefano Petruzzelli, Ruth Tal-Singer, Christopher Compton, Stephen I. Rennard, Ubaldo J. Martin

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Heme Metabolism Genes Downregulated In Copd Cachexia, Ava C. Wilson, Preeti L. Kumar, Sool Lee, Margaret M. Parker, Itika Arora, Jarrett D. Morrow, Emiel F.M. Wouters, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Alvar Agusti, Ruth Tal-Singer, Mark T. Dransfield, J. Michael Wells, Surya P. Bhatt, George Washko, Victor J. Thannickal, Hemant K. Tiwari, Craig P. Hersh, Peter J. Castaldi, Edwin K. Silverman, Merry-Lynn N. Mcdonald

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (<  20 kg/m

RESULTS: The prevalence of …

Improving The Evaluation Of Copd Exacerbation Treatment Effects By Accounting For Early Treatment Discontinuations: A Post-Hoc Analysis Of Randomized Clinical Trials., Agnieszka Król, Robert Palmér, Virginie Rondeau, Stephen I. Rennard, Ulf G. Eriksson, Alexandra Jauhiainen

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment. Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself. Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates. We focus on the hypothetical estimand, i.e. …

Agonist-Specific Desensitization Of Pge2-Stimulated Camp Signaling Due To Upregulated Phosphodiesterase Expression In Human Lung Fibroblasts, Francisco J. Nunez, Nancy Schulte, David M. Fogel, Joel Michalski, Stephen I. Rennard, Raymond B. Penn, Myron L. Toews, Rennolds S. Ostrom

Journal Articles: Pulmonary & Critical Care Med

Pulmonary fibrosis is characterized by fibroblasts persisting in an activated form, producing excessive fibrous material that destroys alveolar structure. The second messenger molecule cyclic 3',5'-adenosine monophosphate (cAMP) has antifibrotic properties, and prostaglandin E2 (PGE2) can stimulate cAMP production through prostaglandin E (EP)2 and EP4 receptors. Although EP receptors are attractive therapeutic targets, the effects of long-term exposure to PGE2 have not been characterized. To determine the effects of long-term exposure of lung fibroblasts to PGE2, human fetal lung (HFL)-1 cells were treated for 24 h with 100 nM PGE2 or other cAMP-elevating agents. cAMP levels stimulated by acute exposure to …

Exposure To Household Secondhand Smoke Among Adolescents In Kuwait: Results From Two School-Based Cross-Sectional Studies, Ali H. Ziyab, Mohammad Almari, Abdullah Al-Taiar

Community & Environmental Health Faculty Publications

INTRODUCTION: Detrimental effects of secondhand smoke (SHS) exposure are well established; however, data on SHS exposure among adolescents in Kuwait are lacking. Hence, this study sought to estimate the prevalence of household SHS exposure among two samples of adolescents in Kuwait and assess its variation by socioeconomic status and parental education level.

METHODS: Data from two large school-based cross-sectional studies were analyzed. Adolescents attending public middle (n=3864; aged 11-14 years) and high (n=1959; aged 14-19 years) schools throughout Kuwait were enrolled in 2016-2017, and parental self-reported household SHS exposure was ascertained. Associations were assessed using Poisson regression with robust variance …

Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas

Bioelectrics Publications

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from …

Employee Testing, Tracing, And Disclosure As A Response To The Coronavirus Pandemic, Matthew T. Bodie, Michael Mcmahon

All Faculty Scholarship

As the COVID-19 pandemic continues to devastate the United States, the federal government has largely failed to implement a national program to prevent and contain the virus. As a result, many employers have undertaken their own workplace coronavirus mitigation efforts. This essay examines, in three parts, the legal framework surrounding employer systems of workplace testing, tracing, and disclosure. It first examines the legal issues surrounding employer-mandated COVID-19 testing and temperature checks, especially issues arising under the Americans with Disabilities Act (ADA) and Health Information Portability and Accountability Act (HIPAA). Regarding employer contact tracing efforts, the essay next reviews the multitude …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Classification Models Of Idiopathic Pulmonary Fibrosis Patients, Mohammed Alqawba, Luis R. Rodriguez, Norou Diawara, Rebecca T. Beuschel, Maryann Kaler, Amisha V. Barochia, Stewart J. Levine, Steven D. Nathan, Geraldine Grant

Mathematics & Statistics Faculty Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal interstitial lung disease with no current cure. Progression of IPF is difficult to predict as the clinical course can be highly variable and range from a rapidly deteriorating state to a relatively stable state, or may be characterized by a slow progressive decline. Therefore, the need for an accurate diagnosis and improved tools for monitoring and managing IPF is of paramount importance, all for understanding the mitochondrial structure and the function played in the IPF. Mitochondrial DNA copy number (MtDCN) has been correlated with mortality in IPF patients and is a …

Search For The Cause Of Vaping Associated Lung Injury In Adolescents, Alexandra E. Krueger

All Graduate Theses, Dissertations, and Other Capstone Projects

In August 2019 an unexplained, exponential rise in severe respiratory illnesses in previously healthy young adults, swept across America catching the attention of medical providers. Hospital admissions for lung injury increased 10-fold over two months’ time leaving practitioners scrambling for answers. All affected patients were found to have used e-cigarettes prior to symptoms and endorsed using nicotine and marijuana vape pens. The medical community quickly began to search for the cause of these vaping associated lung injuries. Understanding the mechanism of injury is important in order to assist in educating the public about the risks associated with e-cigarettes. The aim …

Hsp90 Inhibition And Modulation Of The Proteome: Therapeutical Implications For Idiopathic Pulmonary Fibrosis (Ipf), Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Idiopathic Pulmonary fibrosis (IPF) is a catastrophic disease with poor outcomes and limited pharmacological approaches. Heat shock protein 90 (HSP90) has been recently involved in the wound-healing pathological response that leads to collagen deposition in patients with IPF and its inhibition represents an exciting drug target against the development of pulmonary fibrosis. Under physiological conditions, HSP90 guarantees proteostasis through the refolding of damaged proteins and the degradation of irreversibly damaged ones. Additionally, its inhibition, by specific HSP90 inhibitors (e.g., 17 AAG, 17 DAG, and AUY-922) has proven beneficial in different preclinical models of human disease. HSP90 inhibition modulates a complex …

Functional Characterisation Of Cancer-Associated Fibroblasts From Nasopharyngeal Carcinoma, Wee Lin Wong

Student Works (2020-2029)

Nasopharyngeal carcinoma (NPC) remains a major health issue in Southern China and Southeast Asia where the disease is endemic. Whilst the cure rate for early stage NPC is high, patients often present with late stage diseases and have a 5-year survival rate of less than 50%. NPC patients often suffer from severe treatment side effects because of the location of the tumours that is in proximity to various important organs in the head and neck region. Therefore, alternative therapeutic approaches are needed to improve the treatment outcomes and reduce patient morbidity. Targeted therapies are not in routine use to treat …

Substance Use Disorder, Discrimination, And The Cares Act: Using Disability Law To Strengthen New Protections, Kelly K. Dineen, Elizabeth Pendo

All Faculty Scholarship

The COVID-19 pandemic is having devastating consequences for people with substance use disorders (SUD). SUD is a chronic health condition—like people with other chronic health conditions, people with SUD experience periods of remission and periods of exacerbation and relapse. Unlike people with most other chronic conditions, people with SUD who experience a relapse may face criminal charges and incarceration. They are chronically disadvantaged by pervasive social stigma, discrimination, and structural inequities. People with SUD are also at higher risk for both contracting the SARS-CoV-19 virus and experiencing poorer outcomes. Meanwhile, there are early indications that pandemic conditions have led to …

'Terroristic Threats' And Covid-19: A Guide For The Perplexed, Chad Flanders, Courtney Federico, Eric Harmon, Lucas Klein

All Faculty Scholarship

The first few months of the COVID-19 outbreak in the United States saw the rise of a troubling sort of behavior: people would cough or spit on people or otherwise threaten to spread the COVID-19 virus, resulting in panic and sometimes thousands of dollars’ worth of damages to businesses. Those who have been caught doing this — or have filmed themselves doing it — have been charged under so-called “terroristic threat” statutes. But what is a terroristic threat, and is it an appropriate charge in these cases? Surprisingly little has been written about these statutes given their long history and …

Predictive Factors For Identifying Macrolide Responder In Treating Chronic Rhinosinusitis, Kachorn Seresirikachorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: A low-dose macrolide (LDM) has antineutrophilic activity, so they should not work for eosinophilic inflammation. Clinical predictors are required to select favorable patients for LDM therapy appropriately. This study aims to assess individual predictive factors and propose suitable multiple predictive factors for identifying a macrolide responder in treating CRS. Methodology: Prospective cohort study was done in adult CRS patients. Clinical data collection, Lund-Mackay CT score, visual analog scale (VAS), and sino-nasal outcome test 22 (SNOT-22) were assessed. Patients received 150 mg of roxithromycin once daily plus saline irrigation for 12 weeks. VAS was evaluated at every visit. If the …

Understanding The Host Immune Response Against Pseudomonas Aeruginosa To Develop Novel Therapeutics And Vaccines, Emel Sen Kilic

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium that causes a broad range of acute and chronic infections. The high adaptability and emergence of multidrug-resistant strains of this bacterium pose a significant threat to human health. Particularly, pneumonia caused by this pathogen is associated with high morbidity and mortality in immunocompromised patients. To prevent these infections, we aimed to develop novel vaccine strategies by characterizing the host immune response against P. aeruginosa. During respiratory infections, P. aeruginosa first contacts with epithelial cells along the respiratory tract. Using RNA-sequencing, we were able to characterize transcriptional changes of the epithelial cells in …