Medicine and Health Sciences Commons^™

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling., Rakshamani Tripathi, Zulong Liu, Aditi Jain,, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Department of Medical Oncology Faculty Papers

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2^{nd …}

Health Assessment Questionnaire-Disability Index (Haq-Di) Use In Modelling Disease Progression In Diffuse Cutaneous Systemic Sclerosis: An Analysis From The Eustar Database., Yannick Allanore, Sylvie Bozzi, Augustin Terlinden, Doerte Huscher, Caroline Amand, Christina Soubrane, Elise Siegert, László Czirják, Patricia E Carreira, Eric Hachulla, Elisabetta Zanatta, Mengtao Li, Paolo Airò, Fabian A Mendoza, Edoardo Rosato, Oliver Distler

Jefferson Institute of Molecular Medicine Papers and Presentations

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop …

Perspectives And Experiences Of Transgender And Non-Binary Individuals On Seeking Urological Care., Paul H Chung, Sabina Spigner, Vishal Swaminathan, Seth Teplitsky, Rosemary Frasso

Department of Urology Faculty Papers

OBJECTIVE: To describe perspectives and experiences related to urology care-seeking of transgender and non-binary (TGNB) individuals assigned male at birth.

MATERIALS AND METHODS: This HIPAA-compliant study was IRB approved and followed Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines. Through semistructured interviews, perspectives, and experiences of individuals related to urology care-seeking were explored. Open-ended questions were designed to elicit a range of responses rather than quantifiable data. Thematic codes were developed and explicitly defined. Codes pertaining to patient experiences were assessed and described.

RESULTS: Twenty-five TGNB individuals assigned male at birth were interviewed. Participants reported an array of factors that …

Thalamus And Focal To Bilateral Seizures: A Multiscale Cognitive Imaging Study., Lorenzo Caciagli, Luke A Allen, Xiaosong He, Karin Trimmel, Sjoerd B Vos, Maria Centeno, Marian Galovic, Meneka K Sidhu, Pamela J Thompson, Danielle S Bassett, Gavin P Winston, John S Duncan, Matthias J Koepp, Michael R Sperling

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.

METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 …

Inpatient Hospital Performance Is Associated With Post-Discharge Sepsis Mortality., Nicholas M. Mohr, Alexis M. Zebrowski, David F. Gaieski, David G. Buckler, Brendan G. Carr

Department of Emergency Medicine Faculty Papers

BACKGROUND: Post-discharge deaths are common in patients hospitalized for sepsis, but the drivers of post-discharge deaths are unclear. The objective of this study was to test the hypothesis that hospitals with high risk-adjusted inpatient sepsis mortality also have high post-discharge mortality, readmissions, and discharge to nursing homes.

METHODS: Retrospective cohort study of age-qualifying Medicare beneficiaries with sepsis hospitalization between January 2013 and December 2014. Hospital survivors were followed for 180-days post-discharge, and mortality, readmissions, and new admission to skilled nursing facility were measured. Inpatient hospital-specific sepsis risk-adjusted mortality ratio (observed: expected) was the primary exposure.

RESULTS: A total of 830,721 …

Increasing Out Of Bed The Day Of Surgery Documentation For Post-Op Total Hip & Knee Replacements, Alexis Wyeth, Megan Lofink

Abington Jefferson Health Nurse Residency Posters

No abstract provided.

Falls Prevention On An Observation Unit, Robert Rubino, Niveka Cason

Abington Jefferson Health Nurse Residency Posters

No abstract provided.

Nurse Education And Enteral Feedings In Mechanically Ventilated Patients, Georgina Campbell, John Durison, Daniel Russo

Abington Jefferson Health Nurse Residency Posters

No abstract provided.

Fall Reduction Utilizing Continuous Video Monitoring, Jesse Miller

Abington Jefferson Health Nurse Residency Posters

No abstract provided.

Sepsis Education On 5 Beurger, Kevin Galm, Christina Layton, Nicole Camut, Joseph Seo

Abington Jefferson Health Nurse Residency Posters

No abstract provided.

Effectiveness Of The Care Of Persons With Dementia In Their Environments Intervention When Embedded In A Publicly Funded Home- And Community-Based Service Program., Richard H Fortinsky, Laura N Gitlin, Laura T Pizzi, Catherine V. Piersol, James Grady, Julie T Robison, Sheila Molony, Dorothy Wakefield

College of Health Professions Faculty Papers

Background and Objectives: In the absence of effective pharmacotherapy, there is an urgent need to test evidence-based dementia care interventions using pragmatic trial approaches. We present results from a study in which an evidence-based, nonpharmacologic intervention for persons living with Alzheimer's disease and related dementia (ADRD) and their informal caregivers, Care of Persons with Dementia in their Environments (COPE), was tested in a Medicaid and state revenue-funded home and community-based service (HCBS) program.

Research Design and Methods: Using pragmatic trial design strategies, persons living with ADRD and their caregivers were randomly assigned as dyads to receive COPE plus usual HCBS …

Safety And Efficacy Of Soluble Guanylate Cyclase Stimulators In Patients With Heart Failure: A Systematic Review And Meta-Analysis., Waqas Ullah, Maryam Mukhtar, Aws Al-Mukhtar, Rehan Saeed, Margot Boigon, Donald Haas, Eduardo. Rame

Abington Jefferson Health Papers

BACKGROUND: The utility of novel oral soluble guanylate cyclase (sGC) stimulators (vericiguat and riociguat), in patients with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) is currently unclear.

AIM: To determine the efficacy and safety of sGC stimulators in HF patients.

METHODS: Multiple databases were searched to identify relevant randomized controlled trials (RCTs). Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio (RR) on a random effect model.

RESULTS: Six RCTs, comprising 5604 patients (2801 in sGC stimulator group and 2803 placebo group) were included. The primary endpoint (a composite of cardiovascular mortality and …

Early Evidence Of Dose-Dependent Pharmacodynamic Activity Following Treatment With Sy-5609, A Highly Selective And Potent Oral Cdk7 Inhibitor, In Patients With Advanced Solid Tumors, Kyriakos P. Papadopoulos, Manish R. Sharma, Erika Hamilton, Debra Richardson, Babar Bashir, Graeme Hodgson, Nan Ke, Qing Kang-Fortner, Li Zhou, William Zamboni, Hina A. Jolin, Catherine Madigan, Michael J. Kelly, David A. Roth

Department of Medical Oncology Faculty Papers

No abstract provided.

The Difficult Clinical Decision Of Thrombolytic Therapy For Submassive Pulmonary Embolism In A Community Hospital., Qian Zhang, Jonathan Vayalumkal, John Ricely, Daniel L. Gray, Ahmad Raza

Abington Jefferson Health Papers

Submassive or intermediate-risk pulmonary embolism (PE) occurs when an acute PE episode is associated with radiographic evidence of right heart strain without hemodynamic instability. Further risk stratification is important in determining whether systemic thrombolytic therapy should be administered when weighing the risks and benefits. It includes the risk of death from acute PE versus the risk of bleeding. This decision could be further complicated in institutions where there is a lack of complete therapeutic options, which increases the importance of the expertise of a pulmonologist or an intensivist to decide whether rescue reperfusion is needed. We describe the case of …

Characterization Of Indeterminate Breast Lesions On B-Mode Ultrasound Using Automated Machine Learning Models, Shuo Wang, Sihua Niu, Enze Qu, Flemming Forsberg, Annina Wilkes, Alexander Sevrukov, Kibo Nam, Robert F. Mattrey, Haydee Ojeda-Fournier, John R. Eisenbrey

Department of Radiology Faculty Papers

Purpose: While mammography has excellent sensitivity for the detection of breast lesions, its specificity is limited. Adjunct screening with ultrasound may partially alleviate this issue, but also increases false positives, resulting in unnecessary biopsies. This study investigated the use of Google AutoML Vision (Mountain View, CA), a commercially available machine learning service, to both identify and characterize indeterminate breast lesions on ultrasound.

Methods: B-mode images from 253 independent cases of indeterminate breast lesions scheduled for core biopsy were used for model creation and validation. The performances of two sub-models from AutoML Vision, the image classification model and object detection model …

Release And Extraction Of Retained Subfoveal Perfluorocarbon Liquid Facilitated By Subretinal Bss, Vibration, And Gravity: A Case Report., Kosuke Takahashi, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Shinichiro Doi, Ryo Matoba, Yuki Kanzaki, Yoshihiro Yonekawa, Yuki Morizane

Wills Eye Hospital Papers

BACKGROUND: Perfluorocarbon liquid (PFCL) is an effective surgical adjuvant in performing vitrectomy for severe vitreoretinal pathologies such as proliferative vitreoretinopathy and giant retinal tears. However, subretinal retention of PFCL can occur postoperatively and retained PFCL causes severe visual disorders, particularly when PFCL was retained under the fovea. Although several procedures have been proposed for subfoveal PFCL removal, such as direct aspiration or submacular injection of balanced salt solution (BSS) to dislodge the subfoveal PFCL, the retinal damage associated with these procedures has been a major problem. Here, we report a case of subfoveal retention of PFCL for which we performed …

Simvastatin Induces Unfolded Protein Response And Enhances Temozolomide-Induced Cell Death In Glioblastoma Cells., Sanaz Dastghaib, Shahla Shojaei, Zohreh Mostafavi-Pour, Pawan Sharma, John B Patterson, Afshin Samali, Pooneh Mokarram, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva-TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva-TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell …

Updates In Cervical Cancer Screening, Sarah Cokenakes (Hirsh), Md - Pgy 3

Department of Family & Community Medicine Presentations and Grand Rounds

Learning Objectives:

• To review the incidence of cervical cancer in the United States and the relationship between the HPV virus and invasive cervical cancer.
• To review the 2019 ASCCP guidelines and how they differ from 2012 guidelines.
• To discuss use of technology to aid in appropriate decision making and management.

Measurable Residual Disease-Guided Treatment To Prevent Relapse In Acute Myeloid Leukemia And Myelodysplastic Syndrome., Jonathan Pan, Daniel Altman, Lindsay Wilde

Department of Medical Oncology Faculty Papers

No abstract provided.

Evanescent - Issue 2

Evanescent

This special issue of the journal focuses on COVID-19 and racism in medicine. It was guest edited by Danielle Snyderman, MD, CMD, a geriatrician and an assistant professor in the department of family and community medicine at Thomas Jefferson University and the medical director of The Hill at Whitemarsh continuing care retirement community, and Nick Safian, a member of the Sidney Kimmel Medical College class of 2022.

CONTENTS

• Introduction from the Guest Editors, page 1
• Note from the Editor-in-Chief, page 5
• Section I: Poetry, page 7
• Section II: Home Life, page 9
• Section III: Entering the Fray, page 15
• Section …

Bioactivating A Bone Substitute Accelerates Graft Incorporation In A Murine Model Of Vertical Ridge Augmentation, Jinlong Chen, Xue Yuan, Zhijun Li, Daniel J Bahat, Jill A Helms

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: Compared to autologous bone grafts, allogeneic bone grafts integrate slowly, which can adversely affect clinical outcomes. Here, our goal was to understand the molecular mechanisms underlying graft incorporation, and then test clinically feasible methods to accelerate this process.

METHODS: Wild-type and transgenic Wnt "reporter" mice were used in a vertical ridge augmentation procedure. The surgery consisted of tunneling procedure to elevate the maxillary edentulous ridge periosteum, followed by the insertion of bone graft. Micro-computed tomographic imaging, and molecular/cellular analyses were used to follow the bone graft over time. Sclerostin null mice, and mice carrying an activated form of β-catenin …

Do Not Forget Our Pregnant Women During The Covid-19 Pandemic, Gabriel Costa Osanan, Maria Fernanda Escobar Vidarte, Jack Ludmir

Department of Obstetrics and Gynecology Faculty Papers

No abstract provided.

Outcomes Of Venous End-To-Side Microvascular Anastomoses Of The Head And Neck., Matthew Stewart, Perry Hammond, Ishani Khatiwala, Brian Swendseid, Farshid Taghizadeh, Daniel Petrisor, Tingting Zhan, Richard Goldman, Adam Luginbuhl, Ryan Heffelfinger, Larissa Sweeny, Mark K Wax, Joseph M. Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES/HYPOTHESIS: The literature on outcomes of end-to-side (ETS) anastomoses for microvascular reconstruction of the head and neck is limited. This series reviews ETS in free tissue transfer (FTT) across multiple institutions to better understand their usage and associated outcomes.

STUDY DESIGN: Retrospective review of 2482 consecutive patients across three tertiary institutions.

METHODS: Adult patients (> 18) who received a FTT from 2006 to 2019 were included.

RESULTS: Two hundred and twenty-one FTT were identified as requiring at least one ETS anastomosis. These ETS cases had a failure rate of 11.2% in comparison to 3.8% in a cohort of end-to-end (ETE) …

The Triple Helix Of Clinical, Research, And Education Missions In Academic Health Centers: A Qualitative Study Of Diverse Stakeholder Perspectives., Jed D. Gonzalo, Michael Dekhtyar, Kelly J. Caverzagie, Barbara K. Grant, Steven K. Herrine, Abraham M. Nussbaum, Darlene Tad-Y, Earla White, Daniel R. Wolpaw

Division of Gastroenterology and Hepatology Faculty Papers

Introduction: Academic health centers are poised to improve health through their clinical, education, and research missions. However, these missions often operate in silos. The authors explored stakeholder perspectives at diverse institutions to understand challenges and identify alignment strategies.

Methods: Authors used an exploratory qualitative design and thematic analysis approach with data obtained from electronic surveys sent to participants at five U.S. academic health centers (2017-18), with four different types of medical school/health system partnerships. Participants included educators, researchers, system leaders, administrators, clinical providers, resident/fellow physicians, and students. Investigators coded data using constant comparative analysis, met regularly to reconcile uncertainties, and …

Aberrant Recruitment Of Leukocytes Defines Poor Wound Healing In Patients With Recessive Dystrophic Epidermolysis Bullosa., Taylor Phillips, Leonie Huitema, Rodrigo Cepeda, Diego De Los Cobos, Regina Isabella Matus Perez, Mauricio Salas Garza, Franziska Ringpfeil, Bahar Dasgeb, Jouni Uitto, Julio Cesar Salas-Alanis, Vitali Alexeev, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches.

OBJECTIVES: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks.

METHODS: We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by …

Association Of Laminar Airflow During Primary Total Joint Arthroplasty With Periprosthetic Joint Infection., Qiaojie Wang, Chi Xu, Karan Goswami, Timothy L. Tan, Javad Parvizi Md

Rothman Institute Papers

Importance: Whether laminar airflow (LAF) in the operating room is effective for decreasing periprosthetic joint infection (PJI) after total joint arthroplasty remains a clinically important yet controversial issue.

Objective: To investigate the association between operating room LAF ventilation systems and the risk of PJI in patients undergoing total joint arthroplasty.

Design, Setting, and Participants: A retrospective cohort study was conducted of 6972 consecutive patients undergoing primary total knee arthroplasty or total hip arthroplasty at 2 surgical facilities within a single institution from January 1, 2013, to September 15, 2017, with a minimum of 1 year of follow-up. All procedures were …

New Normal For Medical Practice Post Covid-19?, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

Solving Community Sars-Cov-2 Testing With Telehealth: Development And Implementation For Screening, Evaluation And Testing., Aditi Joshi, Resa E. Lewiss, Maria Aini, Bracken Babula, Patricia C. Henwood

Department of Emergency Medicine Faculty Papers

BACKGROUND: Telehealth has emerged as a crucial component of the SARS-CoV-2 pandemic emergency response. Simply stated, telehealth is a tool to provide health care from a distance. Jefferson Health has leveraged its acute care telehealth platform to screen, order testing, and manage patients with COVID-19-related concerns.

OBJECTIVE: This study aims to describe the expansion and results of using a telehealth program to increase access to care while minimizing additional potential exposures during the early period of the COVID-19 pandemic.

METHODS: Screening algorithms for patients with SARS-CoV-2-related complaints were created, and 150 new clinicians were trained within 72 hours to address …

Computational Modeling Analysis Of Generation Of Reactive Oxygen Species By Mitochondrial Assembled And Disintegrated Complex Ii., Nikolay I. Markevich, Lubov N. Markevich, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reactive oxygen species (ROS) function as critical mediators in a broad range of cellular signaling processes. The mitochondrial electron transport chain is one of the major contributors to ROS formation in most cells. Increasing evidence indicates that the respiratory Complex II (CII) can be the predominant ROS generator under certain conditions. A computational, mechanistic model of electron transfer and ROS formation in CII was developed in the present study to facilitate quantitative analysis of mitochondrial ROS production. The model was calibrated by fitting the computer simulated results to experimental data obtained on submitochondrial particles (SMP) prepared from bovine and rat …

Physician Awareness And Adherence To Clinical Practice Guidelines In The Diagnosis Of Vaginitis Patients: A Retrospective Chart Review., Paul Nyirjesy, Wendy M. Banker, Tiffany M. Bonus

Department of Obstetrics and Gynecology Faculty Papers

Vaginitis is one of the main causes of primary care and gynecological visits in the United States. The most common infectious causes are bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis. A physician survey was conducted to measure awareness of vaginitis clinical guidelines and availability of in-office point-of-care (POC) diagnostic tools. Participants were asked to perform a chart review to evaluate diagnostic practices for their symptomatic vaginitis patients. A total of 333 physicians and 984 patient charts were included. Physicians were most familiar with VVC and BV diagnostic guidelines; fewer than half were aware of current trichomoniasis guidelines. Although access …