Medicine and Health Sciences Commons^™

Association Of Initial Sars-Cov-2 Test Positivity With Patient-Reported Well-Being 3 Months After A Symptomatic Illness., Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, B. H. Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A Mcdonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, Graham Nichol

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive …

Study Protocol For The Innovative Support For Patients With Sars-Cov-2 Infections Registry (Inspire): A Longitudinal Study Of The Medium And Long-Term Sequelae Of Sars-Cov-2 Infection, Kelli N O'Laughlin, Matthew Thompson, Bala Hota, Michael Gottlieb, Ian D Plumb, Anna Marie Chang, Lauren E Wisk, Aron J Hall, Ralph C Wang, Erica S Spatz, Kari A Stephens, Ryan M Huebinger, Samuel A Mcdonald, Arjun Venkatesh, Nikki Gentile, B. H. Slovis, Mandy Hill, Sharon Saydah, Ahamed H Idris, Robert Rodriguez, Harlan M Krumholz, Joann G Elmore, Robert A Weinstein, Graham Nichol

Department of Emergency Medicine Faculty Papers

Background: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

Methods: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days …

Analysis Of An Obstetrics Point-Of-Care Ultrasound Training Program For Healthcare Practitioners In Zanzibar, Tanzania., Elizabeth A Hall, Danielle Matilsky, Rachel Zang, Naomasa Hase, Ali Habibu Ali, Patricia C Henwood, Anthony J Dean

Department of Emergency Medicine Faculty Papers

BACKGROUND: A point-of-care ultrasound education program in obstetrics was developed to train antenatal healthcare practitioners in rural Zanzibar. The study group consisted of 13 practitioners with different training backgrounds: physicians, clinical officers, and nurse/midwives. Trainees received an intensive 2-week antenatal ultrasound course consisting of lectures and hands-on practice followed by 6 months of direct supervision of hands-on scanning and bedside education in their clinical practice environments. Trainees were given a pre-course written exam, a final exam at course completion, and practical exams at 19 and 27 weeks. Trainees were expected to complete written documentation and record ultrasound images of at …

Redefining Cardiac Biomarkers In Predicting Mortality Of Inpatients With Covid-19, Juan-Juan Qin, Xu Cheng, Feng Zhou, Fang Lei, Gauri Akolkar, Jingjing Cai, Xiao-Jing Zhang, Alice Blet, Jing Xie, Peng Zhang, Ye-Mao Liu, Zizhen Huang, Ling-Ping Zhao, Lijin Lin, Meng Xia, Ming-Ming Chen, Xiaohui Song, Liangjie Bai, Ze Chen, Xingyuan Zhang, Da Xiang, Jing Chen, Qingbo Xu, Xin-Liang Ma, Rhian M Touyz, Chen Gao, Haitao Wang, Liming Liu, Weiming Mao, Pengcheng Luo, Youqin Yan, Ping Ye, Manhua Chen, Guohua Chen, Lihua Zhu, Zhi-Gang She, Xiaodong Huang, Yufeng Yuan, Bing-Hong Zhang, Yibin Wang, Peter P Liu, Hongliang Li

Department of Emergency Medicine Faculty Papers

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy

Department of Emergency Medicine Faculty Papers

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as …

Antibody-Based Ticagrelor Reversal Agent In Healthy Volunteers., Deepak L. Bhatt, Charles V. Pollack, Jeffrey I. Weitz, Lisa K. Jennings, Sherry Xu, Susan E. Arnold, Bret R. Umstead, Michael C. Mays, John S. Lee

Department of Emergency Medicine Faculty Papers

BACKGROUND: Ticagrelor is an oral P2Y₁₂ inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful.

METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in …

Myocardial Dysfunction After Out-Of-Hospital Cardiac Arrest: Predictors And Prognostic Implications., Yuan Yao, Nicholas James Johnson, Sarah Muirhead Perman, Vimal Ramjee, Anne Victoria Grossestreuer, David Foster Gaieski

Department of Emergency Medicine Faculty Papers

We aim to determine the incidence of early myocardial dysfunction after out-of-hospital cardiac arrest, risk factors associated with its development, and association with outcome. A retrospective chart review was performed among consecutive out-of-hospital cardiac arrest (OHCA) patients who underwent echocardiography within 24 h of return of spontaneous circulation at three urban teaching hospitals. Our primary outcome is early myocardial dysfunction, defined as a left ventricular ejection fraction < 40% on initial echocardiogram. We also determine risk factors associated with myocardial dysfunction using multivariate analysis, and examine its association with survival and neurologic outcome. A total of 190 patients achieved ROSC and underwent echocardiography within 24 h. Of these, 83 (44%) patients had myocardial dysfunction. A total of 37 (45%) patients with myocardial dysfunction survived to discharge, 39% with intact neurologic status. History of congestive heart failure (OR 6.21; 95% CI 2.54-15.19), male gender (OR 2.27; 95% CI 1.08-4.78), witnessed arrest (OR 4.20; 95% CI 1.78-9.93), more than three doses of epinephrine (OR 6.10; 95% CI 1.12-33.14), more than four defibrillations (OR 4.7; 95% CI 1.35-16.43), longer duration of resuscitation (OR 1.06; 95% CI 1.01-1.10), and therapeutic hypothermia (OR 3.93; 95% CI 1.32-11.75) were associated with myocardial dysfunction. Cardiopulmonary resuscitation immediately initiated by healthcare personnel was associated with lower odds of myocardial dysfunction (OR 0.40; 95% CI 0.17-0.97). There was no association between early myocardial dysfunction and mortality or neurological outcome. Nearly half of OHCA patients have myocardial dysfunction. A number of clinical factors are associated with myocardial dysfunction, and may aid providers in anticipating which patients need early diagnostic evaluation and specific treatments. Early myocardial dysfunction is not associated with neurologically intact survival.

An Assessment Of Emotional Intelligence In Emergency Medicine Resident Physicians., Dimitrios Papanagnou, Kathryn Linder, Anuj Shah, Kory Scott London, Shruti Chandra, Robin Naples

Department of Emergency Medicine Faculty Papers

OBJECTIVES: To define the emotional intelligence (EI) profile of emergency medicine (EM) residents, and identify resident EI strengths and weaknesses.

METHODS: First-, second-, and third-year residents (post-graduate years [PGY] 1, 2, and 3, respectively) of Thomas Jefferson University Hospital's EM Program completed the Emotional Quotient Inventory (EQ-i 2.0), a validated instrument offered by Multi-Health Systems. Reported scores included total mean EI, 5 composite scores, and 15 subscales of EI. Scores are reported as means with 95% CIs. The unpaired, two-sample t-test was used to evaluate differences in means.

RESULTS: Thirty-five residents completed the assessment (response rate 97.2%). Scores were normed …

An Assessment Of Emotional Intelligence In Emergency Medicine Resident Physicians., Dimitrios Papanagnou, Kathryn M Linder, Anuh Shah, Kory Scott London, Shruti Chandra, Robin Naples

Department of Emergency Medicine Faculty Papers

Objectives: To define the emotional intelligence (EI) profile of emergency medicine (EM) residents, and identify resident EI strengths and weaknesses.

Methods: First-, second-, and third-year residents (post-graduate years [PGY] 1, 2, and 3, respectively) of Thomas Jefferson University Hospital's EM Program completed the Emotional Quotient Inventory (EQ-i 2.0), a validated instrument offered by Multi-Health Systems. Reported scores included total mean EI, 5 composite scores, and 15 subscales of EI. Scores are reported as means with 95% CIs. The unpaired, two-sample t-test was used to evaluate differences in means.

Results: Thirty-five residents completed the assessment (response rate 97.2%). Scores were normed …

Endothelial Cell-Derived Microparticles From Patients With Obstructive Sleep Apnea Hypoxia Syndrome And Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction., Lixin Jia, Jingyao Fan, Wei Cui, Sa Liu, Na Li, Wayne Bond Lau, Xin-Liang Ma, Jie Du, Shaoping Nie, Yongxiang Wei

Department of Emergency Medicine Faculty Papers

BACKGROUND/AIMS: Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS.

METHODS AND RESULTS: 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater …

Impact Of Superstorm Sandy On Medicare Patients' Utilization Of Hospitals And Emergency Departments., Benoit Stryckman, Lauren Walsh, Brendan G. Carr, Nathaniel Hupert, Nicole Lurie

Department of Emergency Medicine Faculty Papers

INTRODUCTION: National health security requires that healthcare facilities be prepared to provide rapid, effective emergency and trauma care to all patients affected by a catastrophic event. We sought to quantify changes in healthcare utilization patterns for an at-risk Medicare population before, during, and after Superstorm Sandy's 2012 landfall in New Jersey (NJ).

METHODS: This study is a retrospective cohort study of Medicare beneficiaries impacted by Superstorm Sandy. We compared hospital emergency department (ED) and healthcare facility inpatient utilization in the weeks before and after Superstorm Sandy landfall using a 20% random sample of Medicare fee-for-service beneficiaries continuously enrolled in 2011 …

Idarucizumab For Dabigatran Reversal - Full Cohort Analysis., Charles V. Pollack, Paul A. Reilly, Joanne Van Ryn, John W. Eikelboom, Stephan Glund, Richard A. Bernstein, Robert Dubiel, Menno V. Huisman, Elaine M. Hylek, Chak-Wah Kam, Pieter W. Kamphuisen, Jörg Kreuzer, Jerrold H. Levy, Gordon Royle, Frank W. Sellke, Joachim Stangier, Thorsten Steiner, Peter Verhamme, Bushi Wang, Laura Young, Jeffrey I. Weitz

Department of Emergency Medicine Faculty Papers

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.

METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration …

Clinician-Performed Bedside Ultrasound In Improving Diagnostic Accuracy In Patients Presenting To The Ed With Acute Dyspnea., Dimitrios Papanagnou, Michael Secko, John Gullett, Michael Stone, Shahriar Zehtabchi

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Diagnosing acute dyspnea is a critical action performed by emergency physicians (EP). It has been shown that ultrasound (US) can be incorporated into the work-up of the dyspneic patient; but there is little data demonstrating its effect on decision-making. We sought to examine the impact of a bedside, clinician-performed cardiopulmonary US protocol on the clinical impression of EPs evaluating dyspneic patients, and to measure the change in physician confidence with the leading diagnosis before and after US.

METHODS: We conducted a prospective observational study of EPs treating adult patients with undifferentiated dyspnea in an urban academic center, excluding those …

Associations Of Emergency Department Length Of Stay With Publicly Reported Quality-Of-Care Measures., Anna Marie Chang, Amber Lin, Rongwei Fu, K. John Mcconnell, Benjamin Sun

Department of Emergency Medicine Faculty Papers

OBJECTIVE: The Institute of Medicine identified emergency department (ED) crowding as a critical threat to patient safety. We assess the association between changes in publicly reported ED length of stay (LOS) and changes in quality-of-care measures in a national cohort of hospitals.

METHODS: Longitudinal analysis of 2012 and 2013 data from the American Hospital Association (AHA) Survey, Center for Medicare and Medicaid Services (CMS) Cost Reports, and CMS Hospital Compare. We included hospitals reporting Hospital Compare timeliness measure of LOS for admitted patients. We used AHA and CMS data to incorporate hospital predictors of interest. We used the method of …

Factors Associated With Post-Arrest Withdrawal Of Life-Sustaining Therapy., Anne V. Grossestreuer, David F. Gaieski, Benjamin S. Abella, Douglas J. Wiebe, Ari Moskowitz, Daniel J. Ikeda, Jason S. Haukoos, Sarah M. Perman

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Most successfully resuscitated cardiac arrest patients do not survive to hospital discharge. Many have withdrawal of life sustaining therapy (WLST) as a result of the perception of poor neurologic prognosis. The characteristics of these patients and differences in their post-arrest care are largely unknown.

METHODS: Utilizing the Penn Alliance for Therapeutic Hypothermia Registry, we identified a cohort of 1311 post-arrest patients from 26 hospitals from 2010 to 2014 who remained comatose after return of spontaneous circulation. We stratified patients by whether they had WLST post-arrest and analyzed demographic, arrest, and post-arrest variables.

RESULTS: In our cohort, 565 (43%) patients …

Inter-Rater Reliability Of Post-Arrest Cerebral Performance Category (Cpc) Scores., Anne V. Grossestreuer, Benjamin S. Abella, Kelsey R. Sheak, Marisa J. Cinousis, Sarah M. Perman, Marion Leary, Douglas J. Wiebe, David F. Gaieski

Department of Emergency Medicine Faculty Papers

PURPOSE: Cerebral Performance Category (CPC) scores are often an outcome measure for post-arrest neurologic function, collected worldwide to compare performance, evaluate therapies, and formulate recommendations. At most institutions, no formal training is offered in their determination, potentially leading to misclassification.

MATERIALS AND METHODS: We identified 171 patients at 2 hospitals between 5/10/2005 and 8/31/2012 with two CPC scores at hospital discharge recorded independently - in an in-house quality improvement database and as part of a national registry. Scores were abstracted retrospectively from the same electronic medical record by two separate non-clinical researchers. These scores were compared to assess inter-rater reliability …

The Association Between Hemoglobin Concentration And Neurologic Outcome After Cardiac Arrest., Nicholas J. Johnson, Babette Rosselot, Sarah M. Perman, Kalani Dodampahala, Munish Goyal, David F. Gaieski, Anne V. Grossestreuer

Department of Emergency Medicine Faculty Papers

PURPOSE: The purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients.

METHODS: We conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome.

RESULTS: There were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb …

Practice Characteristics Of Emergency Department Extracorporeal Cardiopulmonary Resuscitation (Ecpr) Programs In The United States: The Current State Of The Art Of Emergency Department Extracorporeal Membrane Oxygenation (Ed Ecmo)., Joseph E. Tonna, Nicholas J. Johnson, John Greenwood, David F. Gaieski, Zachary Shinar, Joseph M. Bellezo, Lance Becker, Atman P. Shah, Scott T. Youngquist, Michael P. Mallin, James Franklin Fair, Kyle J. Gunnerson, Cindy Weng, Stephen Mckellar

Department of Emergency Medicine Faculty Papers

PURPOSE: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department.

METHODS: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel.

RESULTS: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. …

Recurrent Violent Injury: Magnitude, Risk Factors, And Opportunities For Intervention From A Statewide Analysis., Elinore Kaufman, Kristin L. Rising, Md, Ms, Douglas J. Wiebe, David J. Ebler, Marie L. Crandall, M. Kit Delgado

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Although preventing recurrent violent injury is an important component of a public health approach to interpersonal violence and a common focus of violence intervention programs, the true incidence of recurrent violent injury is unknown. Prior studies have reported recurrence rates from 0.8% to 44%, and risk factors for recurrence are not well established.

METHODS: We used a statewide, all-payer database to perform a retrospective cohort study of emergency department visits for injury due to interpersonal violence in Florida, following up patients injured in 2010 for recurrence through 2012. We assessed risk factors for recurrence with multivariable logistic regression and …

Acute Post-Disaster Medical Needs Of Patients With Diabetes: Emergency Department Use In New York City By Diabetic Adults After Hurricane Sandy., David C. Lee, Vibha K. Gupta, Brendan G. Carr, Sidrah Malik, Brandy Ferguson, Stephen P. Wall, Silas W. Smith, Lewis R. Goldfrank

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To evaluate the acute impact of disasters on diabetic patients, we performed a geospatial analysis of emergency department (ED) use by New York City diabetic adults in the week after Hurricane Sandy.

RESEARCH DESIGN AND METHODS: Using an all-payer claims database, we retrospectively analyzed the demographics, insurance status, and medical comorbidities of post-disaster ED patients with diabetes who lived in the most geographically vulnerable areas. We compared the patterns of ED use among diabetic adults in the first week after Hurricane Sandy's landfall to utilization before the disaster in 2012.

RESULTS: In the highest level evacuation zone in New …

Right Ventricular Dysfunction After Resuscitation Predicts Poor Outcomes In Cardiac Arrest Patients Independent Of Left Ventricular Function., Vimal Ramjee, Anne V. Grossestreuer, Yuan Yao, Sarah M. Perman, Marion Leary, James N. Kirkpatrick, Paul R. Forfia, Daniel M. Kolansky, Benjamin S. Abella, David F. Gaieski

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction.

METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012.

PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous …

Racial Disparities In Intravenous Recombinant Tissue Plasminogen Activator Use Persist At Primary Stroke Centers., Hugo J. Aparicio, Brendan G. Carr, Scott E. Kasner, Michael J. Kallan, Karen C. Albright, Dawn O. Kleindorfer, Michael T. Mullen

Department of Emergency Medicine Faculty Papers

BACKGROUND: Primary stroke centers (PSCs) utilize more recombinant tissue plasminogen activator (rt-PA) than non-PSCs. The impact of PSCs on racial disparities in rt-PA use is unknown.

METHODS AND RESULTS: We used data from the Nationwide Inpatient Sample from 2004 to 2010, limited to states that publicly reported hospital identity and race. Hospitals certified as PSCs by The Joint Commission were identified. Adults with a diagnosis of ischemic stroke were analyzed. Rt-PA use was defined by the International Classification of Diseases, 9th Revision procedure code 99.10. Discharges (304 152 patients) from 26 states met eligibility criteria, and of these 71.5% were …

Adiporon, The First Orally Active Adiponectin Receptor Activator, Attenuates Postischemic Myocardial Apoptosis Through Both Ampk-Mediated And Ampk-Independent Signalings., Yanqing Zhang, Jianli Zhao, Rui Li, Wayne Bond Lau, Yue-Xing Yuan, Bin Liang, Rong Li, Er-He Gao, Walter J. Koch, Xin-Liang Ma, Ya-Jing Wang

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) is a cardioprotective molecule. Its reduction in diabetes exacerbates myocardial ischemia/reperfusion (MI/R) injury. Although APN administration in animals attenuates MI/R injury, multiple factors limit its clinical application. The current study investigated whether AdipoRon, the first orally active molecule that binds APN receptors, may protect the heart against MI/R injury, and if so, to delineate the involved mechanisms. Wild-type (WT), APN knockout (APN-KO), and cardiomyocyte specific-AMPK dominant negative (AMPK-DN) mice were treated with vehicle or AdipoRon (50 mg/kg, 10 min prior to MI) and subjected to MI/R (30 min/3-24 h). Compared with vehicle, oral administration of AdipoRon to WT …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

Irf8 Suppresses Pathological Cardiac Remodelling By Inhibiting Calcineurin Signalling., Ding-Sheng Jiang, Xiang Wei, Xiao-Fei Zhang, Yu Liu, Yan Zhang, Ke Chen, Lu Gao, Heng Zhou, Xue-Hai Zhu, Peter P. Liu, Wayne Bond Lau, Xin-Liang Ma, Yunzeng Zou, Xiao-Dong Zhang, Guo-Chang Fan, Hongliang Li

Department of Emergency Medicine Faculty Papers

Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits …

Adiponectin Inhibits Oxidative/Nitrative Stress During Myocardial Ischemia And Reperfusion Via Pka Signaling., Yanqing Zhang, Xiao-Liang Wang, Jianli Zhao, Ya-Jing Wang, Wayne Bond Lau, Yue-Xing Yuan, Er-He Gao, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

The cardioprotective effects of adiponectin (APN) against myocardial ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the mechanisms mediating intracellular APN signaling remains incomplete. We recently demonstrate the antioxidant/antinitrative effects of APN are not dependent on AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN, with uncertain relevance to APN cardiac protection. The current study determined whether the antioxidative/antinitrative effect of APN is mediated by PKA. Administration of APN (2 μg/g) 10 min before reperfusion significantly enhanced cardiac PKA activity, reduced oxidative stress, and decreased infarct size. Knockdown of cardiac PKA expression (PKA-KD) by …

Thioredoxin Reductase Was Nitrated In The Aging Heart After Myocardial Ischemia/Reperfusion., Ke Wang, Jie Zhang, Xiaoliang Wang, Xin Liu, Lin Zuo, Kehua Bai, Jianyu Shang, Lu Ma, Teng Liu, Li Wang, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young …

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

The Alternative Crosstalk Between Rage And Nitrative Thioredoxin Inactivation During Diabetic Myocardial Ischemia-Reperfusion Injury., Yi Liu, Yan Qu, Rutao Wang, Yanzhuo Ma, Chenhai Xia, Chao Gao, Jingyi Liu, Kun Lian, Aibing Xu, Xiaoyan Lu, Lu Sun, Lu Yang, Wayne B. Lau, Erhe Gao, Walter Koch, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The receptor for advanced glycation end products (RAGE) and thioredoxin (Trx) play opposing roles in diabetic myocardial ischemia-reperfusion (MI/R) injury. We recently demonstrated nitrative modification of Trx leads to its inactivation and loss of cardioprotection. The present study is to determine the relationship between augmented RAGE expression and diminished Trx activity pertaining to exacerbated MI/R injury in the diabetic heart. The diabetic state was induced in mice by multiple intraperitoneal low-dose streptozotocin injections. RAGE small-interfering RNA (siRNA) or soluble RAGE (sRAGE, a RAGE decoy) was via intramyocardial and intraperitoneal injection before MI/R, respectively. Mice were subjected to 30 min of …

C1q/Tumor Necrosis Factor-Related Protein-3, A Newly Identified Adipokine, Is A Novel Antiapoptotic, Proangiogenic, And Cardioprotective Molecule In The Ischemic Mouse Heart., Wei Yi, Yang Sun, Yuexing Yuan, Wayne Bond Lau, Qijun Zheng, Xiaoliang Wang, Yajing Wang, Xiying Shang, Erhe Gao, Walter J Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

BACKGROUND: Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.

METHODS AND RESULTS: Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury …