Pulmonology Commons^™

Isolated Small Airways Obstruction Predicts Future Chronic Airflow Obstruction: A Multinational Longitudinal Study, Ben Knox Brown, James Potts, Valentina Quintero Santofimio, Cosetta Minelli, Jaymini Patel, Peter Gj Burney, Andre Fs Amaral, Najlaa Mohammed Abass, Dhiraj Agarwal, Asaad A. Nafees

Community Health Sciences

Background: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.
Methods: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25-75) if a result was less than the lower limit of normal.
Results: Median follow-up time was 8.3 years. Chronic airflow obstruction was more likely to develop in participants with …

Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro

Faculty, Staff and Students Publications

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. …

Ten Steps Toward Improving In-Hospital Cardiac Arrest Quality Of Care And Outcomes, Brahmajee K. Nallamothu, Robert Greif, Theresa Anderson, Huba Atiq, Thomaz Bittencourt Couto, Julie Considine, Allan R De Caen, Therese Djärv, Ann Doll, Matthew J. Douma

Department of Anaesthesia

No abstract provided.

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …

Plasma Metabolomics And Quantitative Interstitial Abnormalities In Ever-Smokers, Bina Choi, Raúl San José Estépar, Suneeta Godbole, Jeffrey L Curtis, Jennifer M Wang, Rubén San José Estépar, Ivan O Rosas, Jared R Mayers, Brian D Hobbs, Craig P Hersh, Samuel Y Ash, Meilan K Han, Russell P Bowler, Kathleen A Stringer, George R Washko, Wassim W Labaki

Faculty, Staff and Students Publications

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.

METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles …

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

Increasing Annual Eye Exam Completion For Children With Cystic Fibrosis Receiving Cftr Modulators, Paula Capel, Claire Elson, Stephanie Duehlmeyer, Jessica Haynes, Amanda Conway, Christopher M. Oermann

Posters

Background: CFTR modulators are life-changing therapy for people with CF. During preclinical studies of ivacaftor, cataracts were identified in juvenile rat pups. Subsequently, noncongenital cataracts have been reported in children receiving CFTR modulator therapy [1], so baseline and annual slit lamp eye examinations for cataract development are recommended for children with CF (aged <18). At Children’s Mercy Kansas City (CMKC), our standard practice is to conduct baseline and annual ophthalmologic examinations to assess for cataracts in children with CF prescribed CFTR modulator therapy, but there was no formal process for tracking adherence to this standard and ensuring that examinations were completed. A quality improvement project was undertaken in May 2022 to determine the rate of completion of annual eye exams and increase adherence to our annual monitoring standard.

Methods: To improve adherence to annual monitoring standards, a quality improvement taskforce including CF care team nurses and pharmacists was developed. A database was used to document baseline and follow-up eye examinations. A standardized communication process was developed and deployed that included an eye exam brochure (Figure …

Sex And Gender In Copd And Asthma, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

Inflammatory Activity Of Epithelial Stem Cell Variants From Cystic Fibrosis Lungs Is Not Resolved By Cftr Modulators, Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L Metersky, Matthew Vincent, Christopher P Crum, Richard C Boucher, Harry Karmouty-Quintana, Howard J Huang, Ajay Sheshadri, Burton F Dickey, Kalpaj R Parekh, John F Engelhardt, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Rationale

CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs.

Objectives

To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) …

Individual- And Neighborhood-Level Characteristics Of Lung Cancer Screening Participants Undergoing Telemedicine Shared Decision Making, Christine S. Shusted, Hee-Soon Juon, Brooke Ruane, Brian M. Till, Charnita Zeigler-Johnson, Russell K. Mcintire, Tyler Grenda, Olugbenga Okusanya, Nathaniel R. Evans, Gregory C. Kane, Julie Barta

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Although lung cancer screening (LCS) for high-risk individuals reduces lung cancer mortality in clinical trial settings, many questions remain about how to implement high-quality LCS in real-world programs. With the increasing use of telemedicine in healthcare, studies examining this approach in the context of LCS are urgently needed. We aimed to identify sociodemographic and other factors associated with screening completion among individuals undergoing telemedicine Shared Decision Making (SDM) for LCS.

METHODS: This retrospective study examined patients who completed Shared Decision Making (SDM) via telemedicine between May 4, 2020 - March 18, 2021 in a centralized LCS program. Individuals were …

Surgical Resection Of An Isolated Superficial Temporal Artery Aneurysm, Jake L. Rosen, Archana Babu, Mohammed Irfan Ali, Michael A. Nooromid

Department of Surgery Faculty Papers

In the present report, we describes a case of surgical resection of an isolated superficial temporal artery aneurysm without underlying systemic pathology. Although aneurysms of this sort most commonly occur in the setting of recent trauma, this case demonstrates an uncommon presentation. We hope to further contribute to the literature regarding this condition.

Further Refinement Of The Differentially Methylated Distant Lung-Specific Foxf1 Enhancer In A Neonate With Alveolar Capillary Dysplasia, Przemyslaw Szafranski, Rijutha P Garimella, Haresh Mani, Ryan Hartman, Gail Deutsch, Alan Silk, Alan Benheim, Paweł Stankiewicz

Faculty, Staff and Students Publications

Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80-90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that …

A Myeloid Program Associated With Covid-19 Severity Is Decreased By Therapeutic Blockade Of Il-6 Signaling, Jason A Hackney, Haridha Shivram, Jason Vander Heiden, Chris Overall, Luz Orozco, Xia Gao, Eugene Kim, Nathan West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F Choy, Alexis J Combes, Tristan Courau, Gabriela K Fragiadakis, Arjun Arkal Rao, Arja Ray, Jessica Tsui, Kenneth Hu, Nicholas F Kuhn, Matthew F Krummel, David J Erle, Kirsten Kangelaris, Aartik Sarma, Zoe Lyon, Carolyn S Calfee, Prescott G Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M Hendrickson, Monique G P Van Der Wijst, George C Hartoularos, Tianna Grant, Raymund Bueno, David S Lee, John R Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Chun Jimmie Ye, Thiru Ramalingam, Jacqueline M Mcbride, Fang Cai, Anastasia Teterina, Min Bao, Larry Tsai, Ivan O Rosas, Aviv Regev, Sharookh B Kapadia, Rebecca N Bauer, Carrie M Rosenberger

Faculty, Staff and Students Publications

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. …

A Case Report Of Pneumoretroperitoneum From Blunt Trauma In A Patient With Chronic Obstructive Pulmonary Disease, Annemarie Daecher, Brittany Hartman, James Krueger

Einstein Health Papers

Introduction: Pneumomediastinum is a rare complication of blunt traumatic injury and is thought to be due to the Macklin effect, a pathophysiologic process comprised of three steps: alveolar rupture secondary to blunt injury; air dissecting along bronchovascular sheaths; and spread of pulmonary interstitial edema into the mediastinal space. Pneumomediastinum is rarely associated with pneumoretroperitoneum.

Case Report: We present a case of a patient who suffered a cardiac arrest after a fall during a chronic obstructive pulmonary disease exacerbation, leading to pneumoretroperitoneum.

Conclusion: This case highlights the complications that can arise from blunt trauma and how underlying lung pathology can worsen …

Revisiting Asthma Obstructive Sleep Apnea Overlap: Current Knowledge And Future Needs, Damini Saxena, Ikuyo Imayama, Muhammad Adrish

Faculty, Staff and Students Publications

Asthma and obstructive sleep apnea are highly prevalent conditions with a high cost burden. In addition to shared risk factors, existing data suggest a bidirectional relationship between asthma and OSA, where each condition can impact the other. Patients with asthma often complain of sleep fragmentation, nocturnal asthma symptoms, daytime sleepiness, and snoring. The prevalence of OSA increases with asthma severity, as evidenced by multiple large studies. Asthma may lower the threshold for arousal in OSA, resulting in the hypopnea with arousal phenotype. Epidemiologic studies in adults have shown that OSA is associated with worse asthma severity, increased frequency of exacerbation, …

Hepatic Chylothorax, A Rare Finding In A Patient With Subacute Hepatic Hydrothorax, Oscar Rodrigo Zamudio Herrera, Shadi Jafari-Esfahani, Fatimah Bello

Research Colloquium

Background: The presence of chyle in the pleural space is termed chylothorax. Etiologies include traumatic (iatrogenic, blunt, or penetrating injury) and non-traumatic (non-malignant and malignant). Liver cirrhosis is a rare cause of non-traumatic, nonmalignant chylothorax. We describe a case of a transudative chylothorax in a patient with cirrhosis and hepatic hydrothorax.

Case presentation: A 72-year-old woman presents with complaints of shortness of breath for 7 days, altered mental status, and abdominal distention. Patient has past medical history of diabetes, hypertension, and liver cirrhosis. On arrival, vital signs demonstrated T 96.2 F°, HR 75, RR 16, BP 143/68, and SO2 97%. …

Pneumocystis Jirovecii Pneumonia In A Newly Diagnosed Aids Geriatric Patient, Ashley Sareen, Nathan Tanner, James Fahey

Research Colloquium

Background: Approximately 40% of new HIV infections originate from people who are unaware of their diagnosis. Median time from infection to diagnosis was 3 years in 2015. Cases of newly diagnosed HIV in the geriatric population are rare.

Case Presentation: 71 year old Hispanic man with history of diabetes and anemia presenting to the hospital with generalized weakness, presyncopal episodes, shortness of breath, loose stools, and falls for past two weeks. He is a poor historian so wife contacted to provide detailed history. Patient with 100 pound weight loss in 6 months. Intravenous drug use 30 years ago, and blood …

E-Cigarette Or Vaping Use-Associated Lung Injury (Evali) In A Hispanic Male During The Covid-19 Pandemic, Juan C. Naranjo, Muhammad Jamal, Aramide Tijani, Fatimah Bello

Research Colloquium

Background: Electronic cigarette or vaping product use–associated lung injury established the relationship between vaping products and lung injury. Overlapping clinical manifestations may mimic those of other respiratory conditions including COVID-19. Multiple radiographic findings including diffuse, bilateral, ground-glass infiltrates with lower-lobe predominance, eosinophilic pneumonia, and diffuse alveolar damage have been described. It is important to consider this as an alternative diagnosis, particularly in patients with respiratory symptoms and a history of vaping in the last 90 days due to increased risk of COVID-19 infection and worse outcomes.

Case presentation: A 25-year-old male with a history of polysubstance abuse and frequent E-cigarette …

Heritable Traits And Lung Cancer Risk: A Two-Sample Mendelian Randomization Study, Rowland W Pettit, Jinyoung Byun, Younghun Han, Quinn T Ostrom, Cristian Coarfa, Melissa L Bondy, Christopher I Amos

Faculty, Staff and Students Publications

INTRODUCTION: Lung cancer is a complex polygenic disorder. Analysis with Mendelian randomization (MR) allows for genetically predicted risks to be estimated between exposures and outcomes.

METHODS: We analyzed 345 heritable traits from the United Kingdom Biobank and estimated their associated effects on lung cancer outcomes using two sample MR. In addition to estimating effects with overall lung cancer, adenocarcinoma, small cell lung cancer, and squamous cell lung cancers, we performed conditional effect modeling with multivariate MR (MVMR) and the traits of alcohol use, smoking initiation, average pre-tax income, and educational attainment.

RESULTS: Univariate MR provided evidence for increased age at …

Pulmonary & Critical Care Insider: Issue 3, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 3

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

Lactated Ringer's or Normal Saline in Acute Pancreatitis?

Don’t complain about too many CT scans being ordered by your ED doctor!

Stroke care for intensivists – Not as complicated after …

Examination Of Disparities In Prehospital Encounters For Pediatric Asthma Exacerbations, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David W Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer N Fishe

Faculty, Staff and Student Publications

INTRODUCTION: There are disparities in multiple aspects of pediatric asthma care; however, prehospital care disparities are largely undescribed. This study's objective was to examine racial and geographic disparities in emergency medical services (EMS) medication administration to pediatric patients with asthma.

METHODS: This is a substudy of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial, which includes data from pediatric asthma patients ages 2-18 years. We examined rates of EMS administration of systemic corticosteroids and inhaled bronchodilators by patient race. We geocoded EMS scene addresses, characterized the locations' neighborhood-based conditions and resources relevant to children using …

Atrial Septal Defect Closure Is Associated With Improved Clinical Status In Patients ≤ 10 Kg With Bronchopulmonary Dysplasia, Melissa K Webb, Milenka Cuevas Guaman, S Kristen Sexson Tejtel, Neil Cambronero, Ryan D Coleman, Corey A Chartan, Betul Yilmaz Furtun, Shaine A Morris, Nidhy P Varghese, Natalie M Villafranco

Faculty, Staff and Students Publications

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared …

Bronchopulmonary Dysplasia – Associated Pulmonary Hypertension: An Updated Review, Ahmed El-Saie, Nidhy P Varghese, Melissa K Webb, Natalie Villafranco, Bheru Gandhi, Milenka Cuevas Guaman, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Molecular Insights Using Spatial Transcriptomics Of The Distal Lung In Congenital Diaphragmatic Hernia, Krithika Lingappan, Oluyinka O Olutoye, Abiud Cantu, Manuel Eliezer Cantu Gutierrez, Nahir Cortes-Santiago, J D Hammond, Jamie Gilley, Joselyn Rojas Quintero, Hui Li, Francesca Polverino, Jason P Gleghorn, Sundeep G Keswani

Faculty, Staff and Students Publications

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

Combining Clinical And Biological Data To Predict Progressive Pulmonary Fibrosis In Patients With Systemic Sclerosis Despite Immunomodulatory Therapy, Elizabeth R Volkmann, Holly Wilhalme, Shervin Assassi, Grace Hyun J Kim, Jonathan Goldin, Masataka Kuwana, Donald P Tashkin, Michael D Roth

Faculty, Staff and Student Publications

OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

RESULTS: Among …

Automated Cellular-Level Dual Global Fusion Of Whole-Slide Imaging For Lung Adenocarcinoma Prognosis, Songhui Diao, Pingjun Chen, Eman Showkatian, Rukhmini Bandyopadhyay, Frank R Rojas, Bo Zhu, Lingzhi Hong, Muhammad Aminu, Maliazurina B Saad, Morteza Salehjahromi, Amgad Muneer, Sheeba J Sujit, Carmen Behrens, Don L Gibbons, John V Heymach, Neda Kalhor, Ignacio I Wistuba, Luisa M Solis Soto, Jianjun Zhang, Wenjian Qin, Jia Wu

Faculty, Staff and Student Publications

Histopathologic whole-slide images (WSI) are generally considered the gold standard for cancer diagnosis and prognosis. Survival prediction based on WSI has recently attracted substantial attention. Nevertheless, it remains a central challenge owing to the inherent difficulties of predicting patient prognosis and effectively extracting informative survival-specific representations from WSI with highly compounded gigapixels. In this study, we present a fully automated cellular-level dual global fusion pipeline for survival prediction. Specifically, the proposed method first describes the composition of different cell populations on WSI. Then, it generates dimension-reduced WSI-embedded maps, allowing for efficient investigation of the tumor microenvironment. In addition, we introduce …

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …