Internal Medicine Commons^™

Suspected Interstitial Lung Disease In Copdgene Study, Jonathan A Rose, Aravind A Menon, Takuya Hino, Akinori Hata, Mizuki Nishino, David A Lynch, Ivan O Rosas, Souheil El-Chemaly, Benjamin A Raby, Samuel Y Ash, Bina Choi, George R Washko, Edwin K Silverman, Michael H Cho, Hiroto Hatabu, Rachel K Putman, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale

Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.

Objectives

To define the prevalence and risk factors of suspected ILD and assess outcomes.

Methods

Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DL_CO less than 70% predicted. Multivariable linear, longitudinal, …

Respiratory Function Changes As Early Signs Of Amyotrophic Lateral Sclerosis, Mario Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, James Peter Orengo, Francesca Polverino

Faculty, Staff and Students Publications

BACKGROUND: The current diagnostic criteria for amyotrophic lateral sclerosis (ALS) may remain unsatisfactory for months or years in the early disease. Pulmonary assessment has never been considered useful in the early diagnosis of ALS, and studies of pulmonary function in this patient category are lacking.

OBJECTIVES: The objective of this study was to assess the pulmonary function in subjects with unspecific symptoms of ALS in whom an ALS diagnosis cannot be reached based on the current available guidelines.

METHODS: We performed pulmonary function tests, arterial gas analysis, maximal inspiratory (MIP) and expiratory (MEP) pressure, and respiratory drive (P0.1) assessment in …

Association Of School Infrastructure On Health And Achievement Among Children With Asthma, Tianshi David Wu, Sandra Zaeh, Michelle N Eakin, Kirsten Koehler, Meghan F Davis, Chris Wohn, Ike Diibor, Kevin J Psoter, Curt Cronister, Faith Connolly, Marc Stein, Meredith C Mccormack

Faculty, Staff and Students Publications

OBJECTIVE: To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma.

METHODS: We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and …

Gene Expression Profiles In Cancers And Their Therapeutic Implications, Chad J Creighton

Faculty, Staff and Students Publications

The vast amount of gene expression profiling data of bulk tumors and cell lines available in the public domain represents a tremendous resource. For any major cancer type, expression data can identify molecular subtypes, predict patient outcome, identify markers of therapeutic response, determine the functional consequences of somatic mutation, and elucidate the biology of metastatic and advanced cancers. This review provides a broad overview of gene expression profiling in cancer (which may include transcriptome and proteome levels) and the types of findings made using these data. This review also provides specific examples of accessing public cancer gene expression data sets …

A Facilitated Peer Mentoring Program With A Dedicated Curriculum To Foster Career Advancement Of Academic Hospitalists, Doris Lin, R Michelle Schmidt, Chirayu Shah, Andrew Caruso, Xiaofan Huang, Kristen A Staggers, Joslyn Fisher

Faculty, Staff and Students Publications

INTRODUCTION: In the field of hospital medicine, there is both a limited pool of senior faculty to mentor the rapidly growing number of junior faculty and a lack of career development curricula focused on scholarly activities specific to the needs of the hospitalist. These deficits have resulted in a disproportionately low number of academic hospitalists being promoted to associate and full professor. We implemented a facilitated peer mentoring program with a dedicated curriculum to foster career advancement of academic hospitalists.

METHODS: We recruited 29 academic hospitalists and divided them into five small groups, each guided by one senior faculty. Peer …

Development Of Competency-Based Online Genomic Medicine Training (Cogent), Susanne B Haga, Wendy K Chung, Luis A Cubano, Timothy B Curry, Philip E Empey, Geoffrey S Ginsburg, Kara Mangold, Christina Y Miyake, Siddharth K Prakash, Laura B Ramsey, Robb Rowley, Carolyn R Rohrer Vitek, Todd C Skaar, Julia Wynn, Teri A Manolio

Faculty, Staff and Student Publications

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training …

Tnik Regulation Of Interferon Signaling And Endothelial Cell Response To Virus Infection, Khanh M Chau, Abishai Dominic, Eleanor L Davis, Sivareddy Kotla, Estefani Turcios Berrios, Arsany Fahim, Ashwin Arunesh, Shengyu Li, Dongyu Zhao, Kaifu Chen, Alan R Davis, Minh T H Nguyen, Yongxing Wang, Scott E Evans, Guangyu Wang, John P Cooke, Jun-Ichi Abe, David P Huston, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored.

METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs.

RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log (

SUMMARY: Our findings suggest that …

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

What Can We Learn From Covid-19?: Examining The Resilience Of Primary Care Teams, Ashley M Hughes, Kelley Arredondo, Houston F Lester, Frederick L Oswald, Trang N D Pham, Cheng Jiang, Sylvia J Hysong

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic continues to place an unprecedented strain on the US healthcare system, and primary care is no exception. Primary care services have shifted toward a team-based approach for delivering care in the last decade. COVID-19 placed extraordinary stress on primary care teams at the forefront of the pandemic response efforts. The current work applies the science of effective teams to examine the impact of COVID-19-a crisis or adverse event-on primary care team resilience.

METHODS: Little empirical research has been done testing the theory of team resilience during an extremely adverse crisis event in an applied team setting. …

Reward Sensitivity Predicts The Response To Cognitive Behavioral Therapy For Children With Autism And Anxiety, Matthew J Hollocks, Jeffrey J Wood, Eric A Storch, An-Chuen Cho, Connor M Kerns, Philip C Kendall

Faculty, Staff and Students Publications

Objective: Cognitive-behavioral therapy (CBT) is an effective treatment for anxiety in youth with autism spectrum disorder (ASD). However, research has yet to examine what cognitive characteristics may influence treatment response. The current study investigated decision-making ability and social cognition as potential (a) predictors of differential treatment response to two versions of CBT and (b) moderators of the effect of treatment condition.

Method: The study included 148 children (mean age = 9.8 years) with interfering anxiety and a diagnosis of ASD who were enrolled in a randomized clinical trial comparing two versions of CBT for anxiety (standard and adapted for ASD). …

Corrigendum: Alveolar Macrophages In Lung Cancer: Opportunities And Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

In the published article, there was an error in the article title. Instead of “Alveolar Macrophages in Lung Cancer: Opportunities Challenges”, it should be “Alveolar Macrophages in Lung Cancer: Opportunities and Challenges”.

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Myeloid-Associated Differentiation Marker Is Associated With Type 2 Asthma And Is Upregulated By Human Rhinovirus Infection, Sasipa Tanyaratsrisakul, Alane Blythe C Dy, Francesca Polverino, Mari Numata, Julie G Ledford

Faculty, Staff and Students Publications

BACKGROUND: Human rhinoviruses are known to predispose infants to asthma development during childhood and are often associated with exacerbations in asthma patients. MYADM epithelial expression has been shown to associate with asthma severity. The goal of this study was to determine if MYADM expression patterns were altered in asthma and/or rhinovirus infection and if increased MYADM expression is associated with increased asthma-associated factors.

METHODS: Utilizing H1HeLa cells and differentiated primary human airway epithelial cells (AECs), we measured the expression of MYADM and inflammatory genes by qRT-PCR in the presence or absence of RV-1B infection or poly I:C treatment and with …

A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz

Faculty, Staff and Students Publications

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill …

Documented Adverse Drug Reactions And Discontinuation Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Chronic Kidney Disease, L Parker Gregg, Peter A Richardson, Michael A Herrera, Julia M Akeroyd, Shehrezade A Jafry, Glenn T Gobbel, Sheena Wydermyer, Jennifer Arney, Adriana Hung, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation.

METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented …

Nanocurcumin Combined With Insulin Alleviates Diabetic Kidney Disease Through P38/P53 Signaling Axis, Raghu Ganugula, Nikhil K Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M N V Ravi Kumar

Faculty, Staff and Students Publications

Treatments for diabetic kidney disease (DKD) mainly focus on managing hyperglycemia and hypertension, but emerging evidence suggests that inflammation also plays a role in the pathogenesis of DKD. This 10-week study evaluated the efficacy of daily oral nanoparticulate-curcumin (nCUR) together with long-acting insulin (INS) to treat DKD in a rodent model. Diabetic rats were dosed with unformulated CUR alone, nCUR alone or together with INS, or INS alone. The progression of diabetes was reflected by increases in plasma fructosamine, blood urea nitrogen, creatinine, bilirubin, ALP, and decrease in albumin and globulins. These aberrancies were remedied by nCUR+INS or INS but …

Peptidylarginine Deiminase 2 Citrullinates Mzb1 And Promotes The Secretion Of Igm And Iga, Benjamin Geary, Bo Sun, Ronak R Tilvawala, Leonard Barasa, Konstantin Tsoyi, Ivan O Rosas, Paul R Thompson, I-Cheng Ho

Faculty, Staff and Students Publications

INTRODUCTION: MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T …

Distinct Temporal Trajectories And Risk Factors For Post-Acute Sequelae Of Sars-Cov-2 Infection, Chen Chen, Sairam Parthasarathy, Jacqueline M Leung, Michelle J Wu, Katherine A Drake, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Bellur S Prabhakar, Mujeeb Basit, Mirella Salvatore, Jerry A Krishnan, Charles C Kim

Faculty, Staff and Students Publications

BACKGROUND: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.

METHODS: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.

RESULTS: We identified three phenotypic clusters associated with PASC that could be characterized as …

Quantitative Interstitial Abnormality Progression And Outcomes In The Genetic Epidemiology Of Copd And Pittsburgh Lung Screening Study Cohorts, Bina Choi, Najma Adan, Tracy J Doyle, Ruben San José Estépar, Rola Harmouche, Stephen M Humphries, Matthew Moll, Michael H Cho, Rachel K Putman, Gary M Hunninghake, Ravi Kalhan, Gabrielle Y Liu, Alejandro A Diaz, Stefanie E Mason, Farbod N Rahaghi, Carrie L Pistenmaa, Nicholas Enzer, Clare Poynton, Gonzalo Vegas Sánchez-Ferrero, James C Ross, David A Lynch, Fernando J Martinez, Meilan K Han, Russell P Bowler, David O Wilson, Ivan O Rosas, George R Washko, Raúl San José Estépar, Samuel Y Ash, Copdgene Study And Pittsburgh Lung Screening Study Investigators

Faculty, Staff and Students Publications

BACKGROUND: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.

RESEARCH QUESTIONS: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?

STUDY DESIGN AND METHODS: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the …

A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish

Faculty, Staff and Students Publications

Tumoral amyloidosis, or amyloidoma, is a benign, but rare form of amyloidosis that has been reported with a favorable prognosis following surgical resection in some case reports. We present a case of acute on chronic respiratory failure secondary to extensive growth of a thoracic amyloidoma causing atelectasis of the right lung. Our case patient had greater morbidity due to late presentation and extensive disease at diagnosis, precluding any surgical intervention. Radiation therapy and medical management were unsuccessful in reducing disease burden. Early diagnosis and detection are pivotal to improving survival in patients with isolated thoracic amyloidoma.

Clinical Efficacy Among Patients With Chronic Rhinosinusitis With Nasal Polyps And Clinical Features Of Obstructive Lung Disease: Post Hoc Analysis Of The Phase Iii Sinus-24 And Sinus-52 Studies, Jorge F Maspero, Claus Bachert, Fernando J Martinez, Nicola A Hanania, Benjamin Ortiz, Naimish Patel, Leda P Mannent, Amy Praestgaard, Nami Pandit-Abid, Shahid Siddiqui, Megan Hardin

Faculty, Staff and Students Publications

PURPOSE: To provide a descriptive summary of clinical efficacy and health-related quality of life (HRQoL) measures in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease in the Phase III dupilumab studies SINUS-24 and SINUS-52 (NCT02912468, NCT02898454).

PATIENTS AND METHODS: Patients met a "broad" definition of having clinical features of obstructive lung disease with any of 3 criteria: (i) pre-bronchodilator forced expiratory volume in 1 second (FEV

RESULTS: Across both studies, 131 patients met the "broad" definition, of whom 90 also had asthma, and 115 patients met the "narrow" definition, of whom 74 had …