Translational Medical Research Commons^™

Cardiac Arrest Clinical Outcomes In Patients Presenting With Opioid Overdose, Andrew Toron, Morgan Hutchinson, Md, David Gaieski

Phase 1

Introduction: Understanding opioids and their potential to cause cardiac arrests is integral in learning how to lower mortality rates in patients who overdose on them. Few studies have specifically examined the association of out-of-hospital cardiac arrests with opioid overdoses. We hypothesized that cardiac arrests caused by opioid overdoses will result in longer hospital stays and a higher mortality rate than other cardiac arrests.

Methods: This study is a secondary analysis of data from the Cardiac Arrest Registry to Enhance Survival. Data regarding 35 patients who presented to Jefferson and Methodist hospitals with out-of-hospital cardiac arrests due to opioid overdose …

Reversing Heart Failure With A Ventricular Anchoring Device: Another Hope For Myopathic Mitral Regurgitation., J. Eduardo Rame

Center for Translational Medicine Faculty Papers

No abstract provided.

State-Level Cpr Education Legislation Associated With Higher Survival After Out-Of-Hospital Cardiac Arrest In Older Adults, Megan Barnes, David G. Buckler, Tyler D. Alexander, Marissa Lang, Alexis Zebrowski, Douglas J. Wiebe, Benjamin S. Abella, Brendan G. Carr

Phase 1

Introduction: State-level legislation requiring CPR education prior to high school graduation is associated with an increased likelihood of community-level CPR training. CPR Legislation has also been shown to be associated with increased bystander CPR. We hypothesized that states with CPR Legislation would be associated with higher survival following out-of-hospital cardiac arrest (OHCA).

Methods: Utilizing 2014 Medicare Claims data for emergency department visits and inpatient stays, we identified OHCA via ICD-9-CM code. CPR Legislation data was collected through online statute review. Exposure to CPR Legislation was assessed using the patient state of residence. All disposition categories were considered survival to discharge …

Cardiac Risk Factors Predicting 30/90 Day Readmission Rates In Lumbar Decompression Surgeries, Blake Nourie, Kevin Xiao, Joseph Bechay, Dhruv K.C. Goyal

Phase 1

Preoperative cardiopulmonary disease is known to be a risk factor for perioperative complications in deformity surgery and lumbar fusion procedures, however there is a lack of literature evaluating cardiac risk factors and their influence on readmission rates following lumbar decompression surgery. We want to determine whether preoperative cardiac risk factors influenced the 30 and 90-day readmission rates in patients undergoing lumbar decompression surgery. Patient charts from Rothman Institute between were reviewed for history of preoperative cardiac risk factors such as coronary artery disease, congestive heart failure, myocardial infarction, stroke, cardiac catheterization, stent placement, coronary artery bypass graft, aspirin and/or clopidogrel …

Evaluating Cardiac Anatomy As A Predictor For Success After Pulmonary Vein Isolation For The Treatment Of Atrial Fibrillation, Paul Richter, Evan Rochlis, Ethan Halpern

Phase 1

Introduction: Atrial Fibrillation is a condition characterized by the production of ectopic beats by the heart. One common treatment for Atrial Fibrillation is catheter guided pulmonary vein isolation (PVI), however this treatment is only effective in around 60-70% of the population. Our research hopes to elucidate a link between cardiac anatomy and successful treatment of A-fib by pulmonary vein isolation.

Methods: The medical records for 78 consecutive patients who underwent PVI for atrial fibrillation at Jefferson from July 2013 to March 2016 were gathered. Included in these charts were ECG-gated cardiac CT angiogram and two-year follow up history. Different variables …

Continuous-Flow Left Ventricular Assist Device Outflow Graft Stenting: Indications And Outcomes, Chelsey T. Wood, Mfa, Elizabeth J. Maynes, Md, Thomas J. O'Malley, Md, Rohinton J. Morris, Md, Louis E. Samuels, Md, H. Todd Massey, Md, Vakhtang Tchantchaleishvili

Phase 1

Introduction: Stenosis in the continuous-flow left ventricular assist device (CF-LVAD) outflow graft can be caused by various mechanical and anatomical factors. Increasingly, percutaneous management has been utilized to re-establish adequate CF-LVAD flow. We sought to evaluate indications for such interventions and their outcomes.

Methods: An electronic search was performed to identify all studies in the English literature reporting CF-LVAD outflow graft stenting for various etiologies. Twenty-one studies consisting of 26 patients were included in the analysis.

Results: Median patient age was 59 years [45.8-67.0] and 65.4% (17/26) were male. 58.3% (14/24) of patients had HeartWare HVAD, 37.5% (9/24) had HeartMate …

The Impact Of Native Language Status On The Frequency Of Heart Failure Readmissions, Cooper Blazek, Dave Katzianer, Md

Phase 1

Introduction. Heart failure readmissions are costly and lead to poor health outcomes. The efficacy of discharge instructions or other outpatient interventions may be affected by patient’s primary language status. The aim of this study is to look at the impact of primary language status on the frequency of heart failure admissions.

Methods. This study was a retrospective chart review of EMRs, on Epic software, at Jefferson academic medical center and community affiliate in Philadelphia, PA between March 2017 and October 2018. Patients were included if they had a principal diagnosis of HF or a diagnosis associated with “acute” heart failure …

Contemporary Epidemiology Of Rising Atrial Septal Defect Trends Across Usa 1991–2016: A Combined Ecological Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal? Methods: Geospatiotemporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse …

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …

C1q/Tnf-Related Protein 3 (Ctrp3) And 9 (Ctrp9) Concentrations Are Decreased In Patients With Heart Failure And Are Associated With Increased Morbidity And Mortality., Chao Gao, Shasha Zhao, Kun Lian, Baibing Mi, Rui Si, Zhijun Tan, Feng Fu, Shuai Wang, Rutao Wang, Xin-Liang Ma, Ling Tao

Center for Translational Medicine Faculty Papers

BACKGROUND: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality.

METHODS: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. …

Transcriptional Up-Regulation Of Relaxin-3 By Nur77 Attenuates Β-Adrenergic Agonist-Induced Apoptosis In Cardiomyocytes., Xiaohua You, Zhifu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun

Center for Translational Medicine Faculty Papers

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 …

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 …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …

Rad Gtpase Deletion Atenuates Post-Ischemic Cardiac Dysfunction And Remodeling, Janet R. Manning, Lakshman Chelvarajan, Bryana R. Levitan, Catherine Nicole Kaminski Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres, Jonathan Satin

Physiology Faculty Publications

The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca²⁺ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of …

Hmgcs2 Is A Key Ketogenic Enzyme Potentially Involved In Type 1 Diabetes With High Cardiovascular Risk., Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq

Center for Translational Medicine Faculty Papers

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to …

Decellularized Wharton's Jelly From Human Umbilical Cord As A Novel 3d Scaffolding Material For Tissue Engineering Applications., Sushma Jadalannagari, Gabriel Converse, Eric Buse, Michael Filla, Maria T. Villar, Antonio Artigues, Adam J. Mellot, Jinxi Wang, Michael S. Detamore, Richard A. Hopkins, Omar S. Aljitawi, C Mcfall

Manuscripts, Articles, Book Chapters and Other Papers

In tissue engineering, an ideal scaffold attracts and supports cells thus providing them with the necessary mechanical support and architecture as they reconstruct new tissue in vitro and in vivo. This manuscript details a novel matrix derived from decellularized Wharton's jelly (WJ) obtained from human umbilical cord for use as a scaffold for tissue engineering application. This decellularized Wharton's jelly matrix (DWJM) contained 0.66 ± 0.12 μg/mg sulfated glycosaminoglycans (GAGs), and was abundant in hyaluronic acid, and completely devoid of cells. Mass spectroscopy revealed the presence of collagen types II, VI and XII, fibronectin-I, and lumican I. When seeded onto …

The Report Of The American Heart Association Task Force On Strategies To Increase Federal Research Funding, Michael R. Rosen, Harold C. Strauss, Holly G. Atkinson, Alfred P. Fishman, Charles K. Francis, Arnold M. Katz, August M. Watanabe, Francois M. Abboud, Myron L. Weisfeldt, William F. Friedman, Bernadine P. Healy, Scott D. Ballin, Claudia Louis, Rodman D. Starke, Wallace G. Frasher

Publications and Research

No abstract provided.