Medicine and Health Sciences Commons^™

A Shorter Door-In-Door-Out Time Is Associated With Improved Outcome In Large Vessel Occlusion Stroke., Adam Sigal, Derek L Isenberg, Chadd K Kraus, Daniel Ackerman, Joseph Herres, Ethan S Brandler, Alexander Kuc, Jason T Nomura, Derek R Cooney, Michael T Mullen, Huaqing Zhao, Nina T Gentile

Einstein Health Papers

Introduction: Endovascular thrombectomy (EVT) significantly improves outcomes in large vessel occlusion stroke (LVOS). When a patient with a LVOS arrives at a hospital that does not perform EVT, emergent transfer to an endovascular stroke center (ESC) is required. Our objective was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in patients undergoing EVT. Methods: We conducted an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry of 2,400 LVOS patients treated at nine ESCs in the United States. We examined the association between DIDO times and 90-day outcomes as measured by the …

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

A Randomized Phase 2 Study Of Vt-1161 For The Treatment Of Acute Vulvovaginal Candidiasis, Stephen R Brand, Jack D Sobel, Paul Nyirjesy, Mahmoud A Ghannoum, Robert J Schotzinger, Thorsten P Degenhardt

Department of Obstetrics and Gynecology Faculty Papers

Background: Acute vulvovaginal candidiasis (VVC) is common among women, but current azole antifungal treatments are often associated with safety and resistance issues. VT-1161 (oteseconazole) is an oral agent with increased selectivity for fungal CYP51. In this phase 2 clinical study, we evaluated the efficacy and safety of VT-1161 vs fluconazole in participants with moderate to severe acute VVC.

Methods: Participants presenting with an acute episode of VVC (n = 55) were randomized to receive VT-1161 300 mg once daily (q.d.) for 3 days, 600 mg q.d. for 3 days, or 600 mg twice daily (b.i.d.) for 3 days or to …

Acute Care Patient Transfer Patterns From Community Hospital Emergency Departments, Dylan Selbst, Michael Knapp, Vasil Mico

Physician Executive Leadership-Plus (PEL-Plus)

No abstract provided.

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Intravesical Rad-Ifnα/Syn3 For Patients With High-Grade, Bacillus Calmette-Guerin-Refractory Or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase Ii Randomized Study., Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney

Department of Medicine Faculty Papers

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, …

Effect Of Oral Semaglutide Compared With Placebo And Subcutaneous Semaglutide On Glycemic Control In Patients With Type 2 Diabetes: A Randomized Clinical Trial., Melanie Davies, Thomas R. Pieber, Marie-Louise Hartoft-Nielsen, Oluf K.H. Hansen, Serge Jabbour, Julio Rosenstock

Department of Medicine Faculty Papers

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection.

Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes.

Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and …

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 …

Iv And Ip Administration Of Rhodamine In Visualization Of Wbc-Bbb Interactions In Cerebral Vessels., Zachary Wilmer Reichenbach, Hongbo Li, John P. Gaughan, Melanie B. Elliott, Ronald Tuma

Department of Neurosurgery Faculty Papers

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we …

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 …

Outdated Dermatologic Drug Samples And Obligations To The Patient., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 37-year-old man with a slightly raised, red, scaly patch on his left arm is seen in the clinic of an academic teaching hospital by a young dermatologist. Following examination and biopsy, he is found to have squamous cell carcinoma in situ. The patient was recently laid off from work and had lost access to his health insurance. He is struggling to make ends meet for his family, so it would be difficult for him to cover any extraneous health-related expenses. Upon relaying this information to the dermatologist, the patient is provided with a full course of 5-fluorouracil …

Does International Normalized Ratio Level Predict Pulmonary Embolism?, Patricia Hansen, Benjamin Zmistowski, Camilo Restrepo, Javad Parvizi, Richard H Rothman

Rothman Institute Faculty Papers

BACKGROUND: Preventing pulmonary embolism is a priority after major musculoskeletal surgery. The literature contains discrepant data regarding the influence of anticoagulation on the incidence of pulmonary embolism after joint arthroplasty. The American College of Chest Physicians guidelines recommend administration of oral anticoagulants (warfarin), aiming for an international normalized ratio (INR) level between 2 and 3. However, recent studies show aggressive anticoagulation (INR > 2) can lead to hematoma formation and increased risk of subsequent infection.

QUESTIONS/PURPOSES: We asked whether an INR greater than 2 protects against pulmonary embolism.

PATIENTS AND METHODS: We identified 9112 patients with 10,122 admissions for joint arthroplasty …

Formulation Of Buprenorphine For Sublingual Use In Neonates., Ellena A Anagnostis, Rania E Sadaka, Linda A Sailor, David E Moody, Kevin C Dysart, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration.

METHODS: Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each …

Efficacy Of Morning-Only Compared With Split-Dose Polyethylene Glycol Electrolyte Solution For Afternoon Colonoscopy: A Randomized Controlled Single-Blind Study., Rebecca Matro, Md, Anastasia Shnitser, Md, Maya Spodik, Md, Constantine Daskalakis, Sc.D, Leo Katz, Md, Alexandra Murtha, Ba, David Kastenberg, Md

Division of Internal Medicine Faculty Papers & Presentations

OBJECTIVES: Administering a purgative close to the time of colonoscopy is optimal for cleansing. The aim of this study was to compare the efficacy and tolerability of morning-only (AM-only) polyethylene glycol electrolyte solution (PEG-ELS) to split-dose (PM/AM) PEG-ELS for afternoon colonoscopy.

METHODS: This was a single-center, prospective, randomized, investigator-blinded, non-inferiority study comparing AM-only to PM/AM PEG-ELS for afternoon outpatient colonoscopy. The primary end point was whole colon prep adequacy. Tolerance and polyp detection were secondary outcomes.

RESULTS: Overall, 125 patients were randomized and 9 withdrew without taking any prep. Of 116 analyzed, 62 received AM-only prep and 54 received PM/AM …

How Does Quality Enter Into Health Care Purchasing Decisions?, Neil I. Goldfarb, Vittorio Maio, Chureen T. Carter, Laura Pizzi, David B. Nash

College of Population Health Faculty Papers

A number of employers, business consortia, and public purchasers are promoting "value-based purchasing" as a way to improve the quality of patient care. Some purchasers are using publicly available information on health plan and provider performance to make their health plan and provider choices, while others are using their market power to drive improvements in patient care and safety. This article examines six key strategies used by purchasers.

An Introductory Lecture To The Course Of Institutes Of Medicine, &C. Delivered In Jefferson Medical College, November 1, 1841, Robley Dunglison, Md

Jefferson Medical College Opening Addresses

No abstract provided.