Translational Medical Research Commons^™

Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, And Epithelial-Mesenchymal Transition By Modulating The Sirt1/Nrf2 Axis, Pritam Saha, Sneha Durugkar, Siddhi Jain, P A Shantanu, Samir R Panda, Aishwarya Jala, Sharad Gokhale, Pawan Sharma, V G M Naidu

Center for Translational Medicine Faculty Papers

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, …

Antimicrobial Stewardship Meets Transitions Of Care: Defining Length Of Therapy For Community-Acquired Pneumonia (Cap), Christopher Whitman, Sarah E. Moore Pharmd, Matthew Song Pharmd, Bcidp, Brian C. Bohn Pharmd, Bcidp, Ashley M. Wilde

The University of Louisville Journal of Respiratory Infections

Introduction: Hospital-based antimicrobial stewardship efforts have traditionally focused on inpatient settings. Antibiotic prescribing at discharge is often an overlooked area of focus for antimicrobial stewardship programs. Discharge prescribing optimization is necessary to combat antibiotic overuse.

Methods: This was an observational, retrospective cohort study at a four–adult community hospital system. Four hundred adult patients admitted with community-acquired pneumonia and discharged with antibiotics were included. The primary outcome was overall (inpatient and discharge) antibiotic length of therapy. The secondary outcome was percentage of patients discharged on a fluoroquinolone who had not received one in the hospital. Descriptive statistics were utilized.

Results: The …

Covid-19, Vaccination, And Heart Transplantation, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Association Of Lung Cancer With Pneumonia And Chlamydia Pneumoniae Infection, Johnny Zakhour Md, Daniel Muller, Alex Glynn, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Introduction: The degree of association and type of causal versus non-causal relationship between pneumonia and lung cancer (LC) are evolving discussions. We reviewed English publications on the degree of association between pneumonia and subsequent LC.

Methods: We searched the PubMed database using key words for pneumonia, LC, and chlamydia infection. We selected peer-reviewed studies of patients with pneumonia and LC. Case reports and other literature reviews were excluded from this review.

Results: Five studies examined the incidence and/or risk of LC for a total of 415,750 patients, and four studies examined cases with Chlamydia pneumoniae chronic infection at the time …

No Difference In Clinical Outcomes For African American And White Patients Hospitalized With Sars-Cov-2 Pneumonia In Louisville, Kentucky, Julio A. Ramirez, Stephen P. Furmanek, Thomas Chandler, Stephen S. Hanson, Dawn Balcom, Subathra Marimuthu, Sathya Krishnasamy, Jose Bordon, Rodrigo Cavallazzi, Amr Aboelnasr, Mahder A. Tella, William A. Mattingly, Ashley M. Wilde, Daisy Sangroula, Demetra Antimisiaris, Donghoon Chung, Guillermo Cabral, Gabino R Fernandez-Botran, Jiapeng Huang, Martin Gnoni, Ozan Akca, Paul Schulz, Phillip F. Bressoud, Priya Krishnan, Sally Suliman, William P. Mckinney, Bryan Moffett, Leslie A Wolf, Mark Burns, Alex Glynn, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Current literature indicates that African American individuals are at increased risk of becoming infected with the SARS-CoV-2 virus and suffer higher SARS-CoV-2-related mortality rates. However, there is a lack of consensus as to how the clinical outcomes of African American patients differ from those of other groups. The objective of this study was to define the clinical outcomes of African American and White hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) in Louisville, Kentucky.

Methods: This was a retrospective cohort study of hospitalized patients with SARS-CoV-2 CAP at eight hospitals in Louisville, Kentucky. Severity of CAP at time of hospitalization …

The Population Affected By The Syndemic Of Covid-19 And Poverty Is More Likely To Be Hospitalized With Sars-Cov-2 Pneumonia, Julio A. Ramirez, Stephen P. Furmanek, Meredith Cahill, Stephen S. Hanson, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Background

Lockdown measures to control COVID-19 have exacerbated the poverty epidemic. We hypothesized that the synergistic interaction of COVID-19 and poverty epidemics favors the development of more severe forms of COVID-19 in the population living in poverty. To test this hypothesis, we assessed whether an ecological association exists between the geographic distribution of hospitalized patients with SARS-CoV-2 pneumonia and markers of poverty in the city of Louisville, KY.

Methods

Using the geomasked home addresses of hospitalized patients with SARS-CoV-2 pneumonia in the city of Louisville, a kernel density heatmap was created. Kuldorff’s spatial scan statistic was used to calculate areas …

Streptococcus Anginosus Lung Infection And Empyema: A Case Report And Review Of The Literature, Nishita Tripathi, Kuldeep Ghosh, Anupama Raghuram

The University of Louisville Journal of Respiratory Infections

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for …

Defining Early And Late Clinical Outcomes In Patients With Sars-Cov-2 Pneumonia, Julio A. Ramirez, Jose Bordon, Rodrigo Cavallazzi, Stephen P. Furmanek, Jiapeng Huang, Timothy L. Wiemken, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Characteristics And Outcomes Of Adults Hospitalized With Sars-Cov-2 Community-Acquired Pneumonia In Louisville, Kentucky, Julio A. Ramirez, Jose Bordon, Rodrigo Cavallazzi, Stephen P. Furmanek, Amr Aboelnasr, Mahder A. Tella, William A. Mattingly, Ashley M. Wilde, Daisy Sangroula, Demetra Antimisiaris, Donghoon Chung, Guillermo Cabral, Gabino R Fernandez-Botran, Jiapeng Huang, Martin Gnoni, Ozan Akca, Paul Schulz, Phillip F. Bressoud, Priya Krishnan, Sally Suliman, Sathya Krishnasamy, Stephen S. Hanson, William P. Mckinney, Harpal Sandhu, Leslie A Wolf, Mark Burns, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY.

Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized at eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate on chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were …

Anesthesia Services In The Time Of Covid, James Chen, Daisy Sangroula, Katelyn Williams, Sydney Pham, Ozan Akca, Jiapeng Huang, Sean Clifford

The University of Louisville Journal of Respiratory Infections

Our hospital is a 400-bed, Level-1 trauma center with 78 intensive care unit (ICU) beds serving the greater Louisville metropolitan area. The COVID-19 pandemic forced our hospital to re-evaluate our core business operations and to develop a coherent response to a fluid situation. Between March 15 and May 15, 2020, the University of Louisville Hospital admitted more than 100 COVID-19 inpatients; approximately 30 were admitted to the ICU, and most required endotracheal intubation. The following review describes our Department of Anesthesiology \& Perioperative Medicine foci, actions, and rationale during the COVID-19 pandemic. While we hope not to experience another pandemic …

Retrospective Review Of Fluoroscopic Swallowing Studies And Outcomes At An Academic Health Center, Rachel Strock, Priyha Mahesh, Baskaran Sundaram, Md, Gregory C. Kane, Md

Phase 1

Introduction: Aspiration is often associated with underlying medical conditions and can cause pneumonia or death. Aspiration risk can be assessed via video fluoroscopic swallowing study (VFSS) or barium swallow (BaSw). We aimed to assess the diagnoses and clinical course of patients who were evaluated for potential aspiration through VFSS or BaSw to determine if there is a degree of aspiration that increases the risk of developing pneumonia and/or death.

Methods: We conducted a retrospective chart review of 374 patients in TJUH who were evaluated via VFSS or BaSw from January 1 to June 30, 2017. We recorded the degree and …

A Man With Acute Severe Pneumonia: Case Discussion From The University Of Louisville Hospital, Viswanathan Nagarajan, Srinivas R. Dontineni, Veronica Corcino, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Assessment Of Pneumonia Severity Indices As Mortality Predictors, Connor L. English, Thomas Chandler, Brian E. Guinn, Stephen P. Furmanek, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

BACKGROUND

The leading cause of infectious disease death in the United States is community-acquired pneumonia (CAP). Several pneumonia severity indices exist and are widely used as tools to assist physicians regarding site of care based on risk of death. However, limited data exists that discerns which of the most commonly used severity scores is the best predictor of mortality across multiple time points. The objective of this study is to determine the best mortality predictor at different time points between four of the most commonly used pneumonia severity scores.

METHODS

This was a secondary analysis of a prospective, multicenter, population-based, …

Towards Multi-Lingual Pneumonia Research Data Collection Using The Community-Acquired Pneumonia International Cohort Study Database, William A. Mattingly, Kimberley A. Buckner, Senen Pena

The University of Louisville Journal of Respiratory Infections

Background: Although multilingual interfaces are preferred by most users when they have a choice, organizations are often unable to support and troubleshoot problems involving multiple user languages. Software that has been structured with multiple languages and data interlinking considerations early in its development is more likely to be easily maintained. We describe the process of adding multilingual support to the CAPO international Cohort study database using REDCap.

Methods: Using Google Translate API we extend the supported Spanish language version of REDCap to the most recent version used by CAPO, 8.1.4. We then translate the English data dictionary for CAPO to …

Clinical Research In Pneumonia: Role Of Artificial Intelligence, Timothy L. Wiemken, Robert R. Kelley, William A. Mattingly, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Continuum Of Disease From Community-Acquired Pneumonia To Multiple Organ Dysfunction Syndrome, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Exploring The Role Of Ceftaroline In The Treatment Of Community-Acquired Pneumonia, Zachary Meyer

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of File TM Jr, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, Llorens L, Critchley IA, Thye DA, FOCUS 1 investigators. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii19-32. doi: 10.1093/jac/dkr096

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

Communication Between Clinicians And The Hospital-Based Microbiology Laboratory: Strategies For 2018 And Beyond, Hans H. Liu

The University of Louisville Journal of Respiratory Infections

No abstract provided.

One-Year Mortality In Patients With Community-Acquired Pneumonia, Paula Peyrani, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Pneumonia remains a common cause of morbidity and mortality in the US. Although, communityacquired pneumonia (CAP) has traditionally been considered an acute process, more recently, data have emerged showing that patients surviving an episode of CAP are at increased risk of death long after hospital discharged. In this descriptive review, we examine the current knowledge of long-term mortality and propose a hypothesis explaining the pathogenesis of long-term mortality in patients with CAP.

Pneumonia Research And The Omics Revolution: It Is Time For Pneumomics, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Community-Acquired Pneumonia Organization (Capo) Cloud-Based Research Platform (The Capo-Cloud): Facilitating Data Sharing In Clinical Research, William A. Mattingly, Timothy L. Wiemken, Stephen P. Furmanek, Paula Peyrani, Robert R. Kelley, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Pneumonia is a costly and deadly respiratory disease that afflicts millions every year. Advances in pneumonia care require significant research investment and collaboration among pneumonia investigators. Despite the importance of data sharing for clinical research it remains difficult to share datasets with old and new investigators. We present CAPOCloud, a web-based pneumonia research platform intended to facilitate data sharing and make data more accessible to new investigators.

Methods: We establish the first two use cases for CAPOCloud to be the automatic subsetting and constraining of the CAPO database and the automatic summarization of the database in aggregate. We use …

Clinical & Translational Research In Pneumonia: Defining A Research Agenda For Today And Tomorrow, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

From the Editor in Chief

The reason for this special supplement of the Journal is to inform readers of a scientific research conference supported by the National Institutes of Health (NHI). The NIH Research Conference Grant (R13) supports high quality scientific conferences in areas that are important to the NIH's mission and to the public health. We just received notification that the National Heart, Lung, and Blood Institute (NHLBI) has approved the application for an international research conference entitled: DzClinical & Translational Research in Pneumonia: Defining a Research Agenda for Today and Tomorrowdz. The conference will be held on Wednesday, …

Neutrophil Function In Elderly Patients Hospitalized With Community- Acquired Pneumonia, Jorge Perez San Juan, Lisandra Rodriguez Hernandez, Timothy L. Wiemken, Robert R. Kelley, Rafael Fernandez-Botran, Martin Gnoni, Paula Peyrani, Madhavi J. Rane, Forest W. Arnold, Julio A. Ramirez, Silvia Uriarte, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP.

Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H₂O₂) …

A Review Of Macrolide Based Regimens For Community-Acquired Pneumonia, Forest W. Arnold, Leslie A. Beavin

The University of Louisville Journal of Respiratory Infections

Community-acquired pneumonia (CAP) has significant morbidity and mortality. The Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines recommend two antimicrobial regimens for hospitalized patients with CAP, one of which includes a macrolide, and one of which does not. Both regimens have antimicrobial properties, but macrolides also possess immunomodulatory properties. Macrolides, however, may also have potential arrhythmia adverse effects. The purpose of this review is to provide an update of studies evaluating outcomes for patients with CAP treated with or without a macrolide-based regimen. Two recent randomized controlled trials conflict with each other regarding the benefit versus noninferiority of including …

Hospital-Based Surveillance Of Invasive Pneumococcal Disease And Pneumonia In South Bangalore, India., R Nisarga, R Premalatha, Shivananda, Kl Ravikumar, U Shivappa, A Gopi, Sb Chikkadasarahalli, R Batuwanthudawe, Paul E. Kilgore, Sa Kim, I Balter, S Jouve, J Ye, M Moscariello

Paul E. Kilgore

OBJECTIVE: To estimate the incidence of invasive pneumococcal disease and pneumonia, distribution of pneumococcal serotypes, and antibiotic susceptibility in children aged 28 days to <60 months. DESIGN: Hospital-based surveillance. SETTING: South Bangalore, India. PARTICIPANTS: 9950 children aged 28 days to <60 months with clinical suspicion of invasive pneumococcal disease or pneumonia. RESULTS: The estimated at-risk population included 224,966 children <5 years of age. Forty cases of invasive pneumococcal disease were identified. Estimated invasive pneumococcal disease incidence was 17.8/100,000 with incidence being highest among children aged 6 months to <12 months (49.9/100,000). Clinical pneumonia syndrome was the most frequent diagnosis (12.5/100,000). Pneumococcal serotypes included: 6A (n=6, 16.7%); 14 (n=5, 13.9%); 5 (n=4, 11.1%); 6B (n=4, 11.1%); 1, 18C, and 19A (n=3 each, 8.3%); 9V (n=2, 5.6%); and 3, 4, 10C, 18A, 18F, and 19F (n=1 each, 2.8%). Serotypes 6A, 14, 6B, 1, 18C, 19A, 9V, 4, 10C, and 18A showed antibiotic resistance. Clinical pneumonia incidence was 2109/100,000, with incidence being highest among children aged 28 days to <6 months (5033/100,000). Chest radiograph-confirmed pneumonia incidence was 1114/100,000, with incidence being highest among children aged 28 days to <6 months (2413/100,000). CONCLUSIONS: Invasive pneumococcal disease and pneumonia were found to be common causes of morbidity in young children living in South Bangalore, India.