Medicine and Health Sciences Commons^™

Genome-Scale Crispr Screening Identifies Cell Cycle And Protein Ubiquitination Processes As Druggable Targets For Erlotinib-Resistant Lung Cancer., Jieun Lee, Ahyoung Choi, Sung-Yup Cho, Yukyung Jun, Deukchae Na, Ahra Lee, Giyong Jang, Jee Young Kwon, Jaesang Kim, Sanghyuk Lee, Charles Lee

Faculty Research 2021

Erlotinib is highly effective in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, despite initial favorable responses, most patients rapidly develop resistance to erlotinib soon after the initial treatment. This study aims to identify new genes and pathways associated with erlotinib resistance mechanisms in order to develop novel therapeutic strategies. Here, we induced knockout (KO) mutations in erlotinib-resistant human lung cancer cells (NCI-H820) using a genome-scale CRISPR-Cas9 sgRNA library to screen for genes involved in erlotinib susceptibility. The spectrum of sgRNAs incorporated among erlotinib-treated cells was substantially different to that of the untreated cells. Gene set analyses …

Targeting Critical Kinases And Anti-Apoptotic Molecules Overcomes Steroid Resistance In Mll-Rearranged Leukaemia., Anne P De Groot, Yoriko Saito, Eiryo Kawakami, Mari Hashimoto, Yuki Aoki, Rintaro Ono, Ikuko Ogahara, Saera Fujiki, Akiko Kaneko, Kaori Sato, Hiroshi Kajita, Takashi Watanabe, Masatoshi Takagi, Daisuke Tomizawa, Katsuyoshi Koh, Mariko Eguchi, Eiichi Ishii, Osamu Ohara, Leonard D. Shultz, Shuki Mizutani, Fumihiko Ishikawa

Faculty Research 2021

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL.

METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain …

Utilizing On-Line Interactive, Adaptive Technology In Healthcare Education – Interactive Skill-Building Workshop, Zilola Khashimova

Physician Assistant Studies | Faculty Conference Presentations

This workshop will show how interactive online resources can be used by healthcare educators to enhance a classroom course or for distance learning, including self-directed modules and learning activities that could be converted to virtual interactions. It will showcase the technology that is available and how to incorporate it into existing courses to utilize what research has shown increases student acceptance and learning outcomes.

Intramedullary Spinal Cord Lesions In Children, Ummey Hani, Sameer Saleem Tebha, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Paediatric intramedullary spinal cord lesions are uncommon pathologies, prone to result in dismal prognosis if not managed promptly and aggressively. While children usually present in good functional grades compared to adults, early recognition and treatment is important to improve outcomes. In this review, we present tumour demographics, patient factors, and treatment modalities of intramedullary spinal cord lesions in paediatric patients.

Complete Versus Subtotal Resection Of Paediatric Craniopharyngioma, Wardah Pervez, Saqib Kamran Bakhshi, Farhan A. Mirza, Muhammad Shahzad Shamim

Section of Neurosurgery

Optimal management of craniopharyngioma is challenging and requires multidisciplinary efforts for a successful outcome. The debate over radical versus a conservative resection followed by radiotherapy, continues. Current literature reports no difference in disease freedom and overall survival between the two surgical viewpoints, and favours conservative resection and radiotherapy, leading to lower morbidity and superior functional outcomes.

Eccrine Spiradenoma: A Rare Adnexal Tumour With Atypical Presentation: A Case Report, Adnan Salim, Muhammad Usman Tariq, Sana Zeeshan

Section of Neurosurgery

First described in 1934, eccrine spiradenoma (ES) is a rare, benign adnexal tumour arising from eccrine sweat glands. It commonly presents as a slow-growing nodule on the upper trunk, and head and neck region, mostly in the age bracket of 15-35 years, with no gender preference. While no established guidelines exist for optimal management of malignant ES, some therapies have been studied. The diagnosis of this entity is extremely important as it can harbour a malignant component with disastrous outcomes which may be missed due to its strong resemblance to benign lesions, such as a papilloma. Here, we present the …

Project Yes! Youth Engaging For Success: A Randomized Controlled Trial Testing A Peer Mentoring Approach Among Hiv-Positive Adolescents And Young Adults In Ndola, Zambia, Julie Denison, Virginia M. Burke, Sam Miti, Bareng A.S. Nonyane, Christiana Frimpong, Katherine G. Merrill, Elizabeth A. Abrams, Jonathan Kaunda Mwansa

HIV and AIDS

This research addresses the gaps in knowledge about how to best support adolescents and young adults transitioning to HIV self-management in the context of both child-focused and adult-focused HIV care settings. Johns Hopkins University, in partnership with the Arthur Davison Children’s Hospital, implemented this study through the USAID-funded Project SOAR (led by the Population Council).

Effects Of Intravenous Iron Versus Oral Iron For Treatment Of Anemia In Pregnancy On Maternal And Fetal Outcomes: A Systematic Review And Meta-Analysis, Sarah Chen, Julia Burd, Md, Rupsa Boelig, Md

Phase 1

Introduction: Anemia during pregnancy can lead to preterm birth, low fetal birthweight, and poorer neonatal neurological outcomes. The purpose of this study was to compare maternal and fetal outcomes following intravenous (IV) versus oral iron supplementation for iron-deficiency anemia during pregnancy.

Methods: We searched MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) comparing IV versus oral iron supplementation for iron-deficiency anemia during pregnancy. Studies were included in this meta-analysis if they reported maternal and fetal hematologic outcomes. The relative risk (RR) or standard mean difference (SMD) of IV iron supplementation …

Sperm Donor Attitudes And Experiences On Direct-To-Consumer Genetic Testing, Sascha Wodoslawsky, Joy Fatunbi, Md, Andrea Braverman, Md

Phase 1

Introduction: Direct-to-consumer (DTC) genetic testing provides a way for genetically linked persons to connect, threatening the anonymity promised by sperm banks to past sperm donors. This study will assess whether these testing resources have changed attitudes of previous donors on donation and their likelihood to donate again.

Methods: A cross-sectional survey was distributed to sperm donors between 1980 and 2020 at Fairfax Cryobank, measuring variables including demographics and donor attitudes on DTC testing. The Qualtrics survey platform aggregated responses and descriptive statistics were used to report outcomes.

Results: Of the 364 responses, 72.8% of donors had not participated …

Effects Of Continuous Positive Airway Pressure (Cpap) Sleep Apnea Treatment On Mild Cognitive Impairment (Mci) And Cardiovascular Risk, Olivia Taylor, Cynthia Cheng, Md, Phd

Phase 1

There is a documented association between sleep apnea and earlier onset of cognitive impairment later in life. We hypothesize that nightly treatment with CPAP therapy will improve MCI status as estimated by a panel of neuropsychiatry tests in patients >55 with OSA and concomitant memory complaints. With a prospective cohort design, patients compliant with CPAP therapy are being compared to noncompliant patients and a non-OSA control group. My role in this multi-site project was to screen potential patients from Jefferson’s sleep clinic for eligibility for study enrollment. This study is still ongoing. OSA’s high prevalence makes it a worthwhile endeavor …

Characterizing The Timeline Of Drug Resistant Epilepsy Surgery., Nicole Belliard Martuscelli, Caio Matias, Ashwini Sharan

Phase 1

Introduction: Although early detection and surgery are crucial for positive outcomes in individuals with drug-resistant epilepsy (DRE), a minority of qualifying patients receive it in the US. This retrospective study investigates why some DRE patients who undergo complete pre-surgical assessment end up not receiving surgery.

Methods: We analyzed 211 EPIC charts from all of Jefferson Comprehensive Epilepsy Center's patients who underwent DRE surgical evaluation from 2017 through 2019. To that end, we characterized the DRE surgery timeline and collected data on age, onset of seizures and drug resistance, surgery dates, surgical modalities, and notes that elucidated the reasoning behind …

The Role Of Toll-Like Receptor 4 In The Progression Of Keloids, Madison Brandes, Nishi Srivastava, Neda Nikbakht

Phase 1

Keloids are highly prevalent in the population and their pathogenesis is largely unknown. T-cell lymphoma research shows that toll like receptor-4 (TLR-4) is highly expressed on CD206+ immunosuppressive macrophages and is implicated in maintaining the tumor microenvironment. Additionally, fibronectin, specifically extra domain A (EDA), is highly expressed and is associated with immunosuppression via the TLR-4 pathway. Assuming that keloids mimic the tumor microenvironment, we hypothesize that TLR-4 is implicated in the pathogenesis of keloids. Using keloid tissue samples and normal breast tissue as a control, immunohistochemistry was performed to observe the presence and co-localization of these markers. Three antibodies were …

Assessing Patient Satisfaction And Confidence After Use Of Educational Video To Augment Surgical Consent For Thyroid Surgery, Michelle Schafer, Katie Holland, Alexander Duffy, Kelley Yuan, Marisa Wu, Raphael Banoub, Elizabeth Cottrill

Phase 1

Introduction: Informed consent is a crucial aspect of ethical patient care, yet the increase in surgical complexity presents a challenge in achieve this properly. This study explores the use of an educational video to help standardize the consent process, increase patient retention of information, and promote patient understanding by allowing patients to replay the information remotely as often as needed.

Methods: This is a perspective, survey-based study of adult patients undergoing thyroid surgery. A novel video detailing thyroid surgery containing the standard contents of informed consent was shown to patients after traditional informed consent followed by a survey on …

Effect Of Palmitic Acid On B2 Receptor Expression In Airway Smooth Muscle Cells, John Magagna, Deepak A. Deshpande, Ajay P. Nayak

Phase 1

Introduction: People with asthma and obesity struggle to control asthma flares. B2 agonists are often the acute treatment of choice during these flares, so the decreased asthma control in this population may be due to a decrease in B2 receptor activity. We tested the hypothesis that B2 receptor expression will decrease in airway smooth muscle cells exposed to Palmitic Acid, a saturated fatty acid, compared to Oleic Acid and untreated cells.

Methods: Airway smooth muscle cells were plated and treated with Palmitic Acid and Oleic Acid at 100uM and 200uM concentrations while other untreated cells served as controls. Cells …

Reliability Of Surgical Margin Labels Using 3d Radiographic Software, Heather Ross, Raphael Banoub, Md, Brian Swendseid, Md, Joseph Curry, Md

Phase 1

Introduction: Surgical resection is a primary treatment for head and neck cancers that improves prognosis and quality of life for patients. Margin assessment is a critical component in this process as positive margins are associated with poor clinical outcomes. However, there is a lack of consensus on how surgical margins should be labeled for accurate origin identification. The objective of this project is to determine the difference in interpretation of surgical margin labels between and within Thomas Jefferson otolaryngologists and pathologists.

Methods: Adults with head and neck cancer who underwent surgical resection were identified. Pre-operative head and neck CT DICOM …

Evaluating The Efficacy Of Telestroke Intervention On Stroke Care In A Large Hospital Network, Daniel Joffe, Ahmad Sweid, Daniel Moylan, Charles Morse, Michael Knapp, Pascal Jabbour

Phase 1

Introduction: Telestroke medicine (TM) involves clinical stroke care by digitally connecting patients and their providers to neurovascular specialists to decrease the time to thrombolytic reperfusion during an acute ischemic stroke (AIS). Rapid administration of intravenous tissue plasminogen activator (iv-tPA) improves AIS outcomes yet no large scale research has evaluated the effectiveness of TM. This study proposes that TM utilization across the Jefferson University Hospital network will increase thrombolytic reperfusion rates and improve overall stroke outcomes.

Methods: A retrospective cohort study design with data from a Jefferson Telestroke database contained information for 9,702 patients across 36 hospital affiliates. These patients were …

Assessment Of The Diagnostic Accuracy Of Core Needle Biopsy In The Diagnosis Of Lymphoma, Christopher A. Gardner, Xiangyun Ye, Catherine Tucker, Md, Austin Redilla, Guldeep Uppal, Md, Adam F. Binder

Phase 1

Introduction: Excisional biopsy (EB) of lymph nodes is the gold standard for diagnosing lymphoma. Recent literature suggests that diagnostic techniques such as immunohistochemistry, flow cytometry and FISH/Cytogenetics yield similar diagnostic adequacy rates when paired with less invasive procedures, like Core Needle Biopsy (CNB). We were interested in comparing the diagnostic odds ratio and adequacy of patients suspected of lymphoma who underwent CNB to EB at Thomas Jefferson University Hospital (TJUH).

Methods: We performed a retrospective cohort study on biopsies collected from 01/01/2016 and 12/31/2019 at TJUH. Specimens were considered diagnostically inadequate if there was not enough lesional tissue for …

Timing Of Preoperative Surgical Antibiotic Prophylaxis Prior To One-To-Three Level Elective Lumbar Fusion, Akash Singh, Gregory Schroeder, Md, Jose Canseco, Md, Alexander Vaccaro, Md, Parthik Patel, Md, Ariana Reyes, Md

Phase 1

Introduction: Surgical site infections (SSIs) in patients who have undergone lumbar fusion surgery can be a devastating complication. The aim of this study was to examine the relationship between timing of preoperative antibiotic prophylaxis and adverse outcomes such as SSIs with subgroup analysis stratified by antibiotic type.

Methods: This retrospective cohort included patients having undergone a 1-3 level lumbar fusion who were allocated into 5 groups based on the time from antibiotic administration to incision (Group A = 0-15 min, Group B = 16-30 min, Group C = 31-45 min, Group D = 46 – 60 min, and Group …

The Integration Of Transgender Health Into Jeffmd, Jacob Nair, Bernard Lopez, Md

Phase 1

Purpose: One way to address healthcare disparities experienced by the transgender community is by educating medical students on trans health. Currently, there is not a universal LGBTQ+ curriculum in medical schools, which has resulted in students feeling incompetent and uncomfortable when treating transgender patients. The purpose of this study was to evaluate the current trans health content in JeffMD and remedy any curricular gaps with trans specific content.

Methods: The trans content in JeffMD was identified using a Keyword Search tool, One45 and lecture notes. A survey distributed to all Thomas Jefferson healthcare students regarding their attitudes and knowledge surrounding …

Efficacy Of Articulate Module: Tracheostomy And Laryngectomy Pearls For The Health Care Providers, Sruti Tekumalla, Andrew Piacitelli, Vanessa Christopher, Dimitri Papanagnou, David Cognetti

Phase 1

Purpose: Anatomy, general care and emergency management knowledge of tracheostomies and laryngectomies is crucial in preventing significant morbidity and mortality within the surgical airway population. An Articulate module was made to address and refresh learners on pertinent surgical airway knowledge. Our goal was to assess the efficacy of the new Articulate module, measuring airway knowledge and attitude treating the surgical airway population.

Methods: Residents in anesthesia, emergency medicine, and internal medicine were eligible and consented to participate. Half of participants were given the Articulate module and half were not. All participants were asked to take a follow-up test. The test …

Needs Analysis For Breastfeeding Education At Thomas Jefferson University Hospital, Michal Norry, Julia Switzer, Md

Phase 1

Purpose: There are currently gaps in breastfeeding education for OB/GYN and Family Medicine residents, consequently affecting their confidence in this area of patient care. To address this issue, we are conducting an analysis of the efficacy of the current curriculum to highlight areas for future improvement.

Methods: PGY1-4 residents in the departments of Family Medicine (FM) and Obstetrics and Gynecology (OB/GYN) completed a pre-test before their required annual breastfeeding education on August 6, 2020. We used a validated pre-test from the American Academy of Pediatrics (AAP) which included items assessing the training. Learners self-selected one of two didactic sessions: in …

Patient Characteristics Of A Primary Care-Based Medication-Assisted Treatment Program For Opioid Use Disorder In Philadelphia, Zoe Wong, Lara Weinstein, Md

Phase 1

Introduction: The opioid crisis is a persistent national public health concern, with Philadelphia at its epicenter. Medication-assisted treatment (MAT) programs for opioid use disorder in primary care settings afford greater access to marginalized groups and integration of healthcare services. This study describes patient characteristics of a low-threshold, primary care-based MAT program in Philadelphia.

Methods: 134 patient interviews between February 12, 2019 and March 14, 2020 were retrospectively analyzed. Key characteristic measures included drug and alcohol use history, co-occurring health conditions, history of violence or trauma, and quality of life. The results from the two program locations, Stephen Klein Wellness Center …

The Wic Program: Background, Trends And Factors Associated With Participation Among Wic Eligible Families, Peace Nosa-Omorogiuwa, Cheryl Bettigole

Phase 1

Introduction

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides access to supplemental foods, nutrition education etc. to low-income pregnant women, infants and children under 5. Despite being a safety net for nutritionally at-risk individuals, the coverage rates for WIC eligible individuals are far lower than the eligibility rates. This study seeks to understand the history of the WIC program, analyze current trends and discuss factors affecting participation in the WIC program.

Methods

The target population are populations that are eligible for the WIC program. A narrative review of journal articles was conducted. Databases searched were EBSCO …

Urosim, Robert Abishek, Bryan Nardone, Jasmine Wang, Christopher Wetzel, Rob Pugliese

Phase 1

Designing a more cost-efficient method for ureteroscopy simulation training that involves 3D printing an anatomically-accurate model of a patient’s renal pelvicalyceal system.

Exploring Political Awareness And Civic Engagement Among Women Utilizing Mater Services, Cathy Lu, Meghan Gannon, Phd, Msph

Phase 1

Introduction: High levels of civic engagement by United States citizens sustains the integrity of the democratic system. Health organizations, such as The Maternal Addiction Treatment Education and Research (MATER) program, are in a position to help marginalized voting-eligible individuals overcome barriers to voting.

Methods: The target population was women utilizing MATER services. The study design consisted of a survey collecting data including demographic information, political engagement, perceived barriers, and interest in future advocacy. Following the survey, participants were offered more voting resources.

Results: One hundred percent of participants reported utilizing public assistance. Forty-eight percent reported a social network as their …

Strategic Design Development For Malawian Public Health Center Labor & Delivery Suites, Kayla Holston, Mph, Meghan Gannon, Phd, Msph, Christopher Harnish, March, Zayithwa Fabiano, Mbbs, Luis Gadama, Mbbs, Mmed

Phase 1

Introduction: Maternity ward pre-, peri-, and postnatal room sharing creates concerns regarding maternal privacy (particularly confidentiality and dignity), paternal involvement in birthing process, and staff workflow efficiency. This study aimed to understand the current state of the aforementioned concerns and their impact on maternal child bonding and maternal mental health at Queen Elizabeth Central Hospital (QECH).

Methods: At discharge, mothers of birth (MOBs) were surveyed on pre-, peri-, and postnatal experience with regard to privacy and paternal involvement in the birthing process, and then assessed using the Mother to Infant Bonding Scale and Edinburg Depression Scale. Father of births (FOBs) …

Effect Of Patient Perspectives In Teaching Medical Students About Postpartum Depression, Laura Fiorini, Julia Switzer, Md

Phase 1

Purpose: Postpartum Depression (PPD) is frequently undiagnosed in the clinical setting. Barriers to correctly recognizing and diagnosing PPD include lack of specific education during medical school and prioritization of physical health over psychosocial health. Further, to better understand psychologic disorders, medical education should incorporate patient perspectives so that students can fully appreciate the individual impact.

Methods: This study was designed on Qualtrics and circulated to preclinical medical students (MS 1/2) at Thomas Jefferson University. Participants completed a T/F pretest and viewed the included slide deck. Half of the participants were randomized to watch a patient perspective. As a posttest, objective …

Rapid Decline In Telestroke Consults In The Setting Of Covid-19., Syed O. Shah., Robin Dharia, Jaime Stazi, Maureen Deprince, Robert H. Rosenwasswer

Farber Institute for Neuroscience Faculty Papers

Background and Purpose: As coronavirus disease 2019 (COVID-19) continues to be a global pandemic, there is a growing body of evidence suggesting that incidence of diseases that require emergent care, particularly myocardial infarction and ischemic stroke, has declined rapidly. The objective of this study is to quantify our experience of telestroke (TS) consults at a large tertiary comprehensive stroke center during the COVID-19 pandemic.

Methods: We retrospectively reviewed TS consults of patients presenting to our neuroscience network. Those with a confirmed diagnosis of acute ischemic stroke or transient ischemia attack were included. Data were compared from April 1, 2019, to …

The Role Of Mirnas, Mirna Clusters, And Isomirs In Development Of Cancer Stem Cell Populations In Colorectal Cancer., Victoria A Stark, Caroline O B Facey, Vignesh Viswanathan, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss …

Sarcoidosis Presenting As Fatigue And Weakness, Syed Muhammad Zubair, Naveed Haroon Rashid

Section of Pulmonary & Critical Care

Sarcoidosis is a systemic granulomatous disorder of unknown cause that occurs in both men and women of all races. It typically presents in patients after 20 years of age. Sarcoidosis most frequently involves the lung, but up to 30 percent of patients present with extra-thoracic manifestations. It can involve multiple organs to a variable extent and degree. In areas, where tuberculosis is endemic, the diagnosis of sarcoidosis may be overlooked and misdiagnosed because of clinical and radiographic resemblance. Herein, we present a case of a middle-aged man who visited multiple physicians with constitutional symptoms and was treated symptomatically but did …