Translational Medical Research Commons^™

Amelioration Of The Neuroinhibitory Local Environment After Ischemic Injury Through In Situ Astrocyte-To-Neuron Conversion, Abhinav K. Rao, Yu-Chen Chen, Ning-Xin Ma, Zi-Fei Pei, Susan Keefe, Emma Yellin, Miranda Chen, Fu-Han Yang, Xiao-Song He, Gong Chen

Phase 1

Ischemic injury in central nervous system (CNS) often causes severe neuronal loss and activates glial cells. We showed earlier that NeuroD1-mediated astrocyte-to-neuron (AtN) conversion can regenerate a substantial proportion of neurons (~40% of the total) and reconstruct the ischemic injured neural circuits. In this study, we focus on glial changes and blood vessel recovery following AtN conversion. Specifically, we found that ectopic expression of NeuroD1 in the reactive astrocytes after ischemic injury significantly reduced glial reactivity, as shown by less hypertrophic morphology, along with reduced secretion of neuroinhibitory factors such as CSPG and LCN2. As for microglia, we found less …

Is Facet Joint Distraction A Cause Of Postoperative Axial Neck Pain After Acdf Surgery?, Nathan Houlihan, Srikanth N. Divi, Md, Dhruv K.C. Goyal, John J. Mangan, Md, Justin D. Stull, Md, Matthew S. Galetta, Jeffrey A. Rihn, Mark F. Kurd, Md, D. Greg Anderson, Md, Alan S. Hilibrand, Md, Alexander R. Vaccaro, Md, Phd, Mba, Christopher K. Kepler, Md, Mba, Gregory D. Schroeder, Md, Joseph K. Lee, Md

Phase 1

Introduction: Intervertebral distraction in anterior cervical discectomy and fusion (ACDF) has been postulated to injure the degenerative facet joints posteriorly and increase postoperative pain and disability. This study aims to determine if there is a correlation between the amount of facet distraction and postoperative patient reported outcomes.

Methods: A retrospective cohort analysis of patients undergoing ACDF for degenerative pathologies was performed. Each patient received lateral cervical spine x-rays at the immediate postoperative time point and were split into groups based on the amount of facet distraction measured on these films: Group A: < 1.5 mm; Group B: 1.5-2.0 mm; and Group C: > 2.0 mm. Patients reported outcome measures were obtained …

Surgical Pulmonary Embolectomy Outcomes For Acute Pulmonary Embolism, Nicholas D. D'Antonio, Jae Hwan Choi, Md, Thomas J. O'Malley, Md, Elizabeth J. Maynes, Md, Matthew P. Weber, Ms, Martín Mellado, Md, Frances M. West, Md, Taki Galanis, Md, Carin F. Gonsalves, Md, Gregary D. Marhefka, Md, Bharat K. Awsare, Md, Geno J. Merli, Md, Vakhtang Tchantchaleishvili, Md

Phase 1

Introduction: Acute pulmonary embolism (PE) is associated with significant mortality. Surgical embolectomy is a viable treatment option; however, it remains controversial due to variable outcomes. This review investigates patient outcomes following surgical embolectomy for acute PE.

Methods: Electronic search was performed to identify articles reporting surgical embolectomy for treatment of PE. 32 studies were included comprising 936 patients. Demographic, perioperative, and outcome data were extracted and pooled for systematic review.

Results: Mean patient age was 56.3 [95% CI 52.5; 60.1] years and 50% [46; 55] were male. 82% had right ventricular dysfunction [62; 93], 80% [67; 89] had unstable …

Static Vs. Expandable Peek Interbody Cages: A Comparison Of One-Year Clinical And Radiographic Outcomes For One-Level Tlif, Ryan Nachwalter, Parthik Patel, Md, Alexander R. Vaccaro, Md, Phd

Phase 1

Introduction: Degenerative spine disease is a disabling condition affecting many worldwide. Transoforaminal lumbar interbody fusion (TLIF) procedures help stabilize the spine, while improving back and/or leg pain. With the introduction of new implant designs and modifications, focus has shifted to optimizing spinopelvic alignment, fusion rates, and more. This study aims to explore the effect of static versus expandable polyetheretherketone (PEEK) cages on patient-reported outcomes (PROMs) and radiographic outcomes (subsidence, disk height, and alignment parameters).

Materials/Methods: A retrospective cohort study was conducted using a database of patients in a single, high volume academic center. Patient outcomes were obtained from charts and …

Hepatocellular Carcinoma Treated With Microwave Ablation Prior To Liver Transplantation, Nicole Wagner, Amanda Smolock, Michael Markovitz, Varun Danda, Christopher Neely, Warren Maley, Jesse Civan, Colette Shaw

Phase 1

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA.

Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, …

Retrospective Review Of Fluoroscopic Swallowing Studies And Outcomes At An Academic Health Center, Rachel Strock, Priyha Mahesh, Baskaran Sundaram, Md, Gregory C. Kane, Md

Phase 1

Introduction: Aspiration is often associated with underlying medical conditions and can cause pneumonia or death. Aspiration risk can be assessed via video fluoroscopic swallowing study (VFSS) or barium swallow (BaSw). We aimed to assess the diagnoses and clinical course of patients who were evaluated for potential aspiration through VFSS or BaSw to determine if there is a degree of aspiration that increases the risk of developing pneumonia and/or death.

Methods: We conducted a retrospective chart review of 374 patients in TJUH who were evaluated via VFSS or BaSw from January 1 to June 30, 2017. We recorded the degree and …

The Use Of Wearable Technology In The Detection Of Operator Fatigue, James O'Shea, Stanton Miller, Md, Mph

Phase 1

Introduction: Operator fatigue is a prevalent cause of injury and death. Many studies have proven reliable ways of determining operator fatigue through the use of engineering and technological advances including blink rate, lid lag, respiratory rate, cardiac rate, chest expansion, etc. However the implementation of these advances has yet to be utilized. This systematic literature review seeks to elucidate the need for implementation of wearable technology for those who suffer from operator fatigue.

Methods: The target population includes anyone who operates a vehicle including drivers, aviation pilots, train conductors/engineers, marine pilots, operators of heavy machinery, fishermen and professional/overnight drivers. All …

Characteristics And Outcomes Of Patients Discharged Directly Home From A Medical Intensive Care Unit, Preeyal M. Patel, Michele Fiorella, Ms, Ann Zheng, Erika J. Yoo, Md

Phase 1

Introduction: Discharging patients directly home from the ICU is becoming increasingly common, largely driven by decreased ward bed availability. We evaluated readmission patterns of ICU patients discharged directly home.

Methods: Retrospective review was conducted of direct discharges from the ICU to home between June 2017 and June 2019. The primary outcome of interest was 30-day hospital readmission. Patients were dichotomized by “wait-time” between transfer order and hospital discharge (<24 hours or ≥24 hours). Outcomes were compared using t-test, Fisher exact, and chi-squared. Risk-adjustment was performed using the Mortality Probability Model (MPM₀-III). ICU workload was estimated using the nine equivalents of nursing manpower use score (NEMS).

Results: 331 patients were identified, with a mean time of 0.72 [0 - 5.84] …

What Is The Effect Of Iodine Contrast Agents On The Subharmonic Signal Generated From Ultrasound Contrast Agents?, Neal Kalantri, Cara Esposito, Jaydev Dave

Phase 1

Subharmonic-aided pressure estimation (SHAPE) is a technique utilizing subharmonic signals from microbubble-based ultrasound contrast agents (UCA’s) to noninvasively record pressures. Cardiac applications of SHAPE have been demonstrated in canines where low errors (0.19-2.5mmHg) were observed in canine ventricle pressures between the SHAPE technique and pressure catheter measurements. Validation of SHAPE involves simultaneous measurements by a pressure catheter (iodine contrast is used to guide catheter placement) and by SHAPE using UCAs. The goal of this experiment is to determine if mixing Visipaque (iodine contrast, GE Healthcare, Oslo, Norway) and UCAs effects the subharmonic signal.

The study was performed in an in …

Effects Of Neonatal Abstinence Syndrome On Long-Term Growth Parameters, Ayoung Kim, Anastasiya Latushko, Md, Zubair H. Aghai, Md

Phase 1

Introduction: Past studies have shown that babies with Neonatal Abstinence Syndrome (NAS) have lower weight, head circumference, and height at birth. This study aims to compare their growth at 9 and 18 months of age, and to compare growth parameter of NAS infants below 10th percentile to those above 10th percentile at birth.

Methods: In this retrospective review, 260 infants admitted to Jefferson Neonatal Intensive Care Unit between 2006 and 2018 were included. The weight, height, and head circumference at birth, 9 months, and 18 months were collected and correlated by Pearson correlation. The growth parameters of infants below …

Renal Mass Ablation In The Octogenarian And Nonagenarian Population, Callum Hamilton, Amanda Smolock, Md, Colette Shaw, Md, Conor Mckee, Md

Phase 1

Introduction: The gold standard for the management of T1a and T1b renal tumors is partial nephrectomy. This study aims to analyze the outcomes of renal mass thermal ablations as an alternative therapy in the octogenarian and nonagenarian patient population, specifically.

Methods: Departmental database of all percutaneous renal ablations performed between February 2008 and August 2019 was reviewed. 34 tumors were ablated in 19 males and 15 females with a mean age of 84.1 ± 3.1 years (range 80-92 years). Patient demographics, procedural and postprocedural data were evaluated.

Results: Ten microwave and 24 cryoablations were performed, all ablations …

Primary Care Obstructive Sleep Apnea Screening (Pcosa), Alyssa Givens, Risa Goldberg, Cynthia Cheng, Md, Phd

Phase 1

Introduction: Obstructive sleep apnea (OSA) is a largely underdiagnosed disorder of upper airway collapse during sleep. Primary care providers do not routinely screen for OSA. This project aims to determine the yield of using the STOP-BANG questionnaire to identify previously undiagnosed OSA in a primary care population.

Methods: This prospective quality improvement pilot project included 181 patients of the Jefferson Department of Family Medicine identified as high-risk for OSA based on 3 EMR-based search criteria taken from STOP-BANG: hypertension, age >50 years, and BMI >35 kg/m². We attempted contact with patients by mail, followed by up to …

Predictors Of Functional Outcomes Following Operative Treatment Of Acute Achilles Tendon Ruptures, Andrew Fisher, Ryan Rogero, Joseph O'Neil, Md, Daniel Fuchs, Md, Steven Raikin, Md

Phase 1

Introduction: Previous studies involving operative management of Achilles tendon ruptures have attempted to determine if patient factors influence outcomes. No previous study has attempted to identify outcome predictors in patients exclusively undergoing surgical repair. The purpose of this study is to determine if any injury or patient variables were predictive of outcomes following operative management of Achilles ruptures.

Methods: Patient demographics including age, sex, body mass index (BMI), comorbidities (diabetes mellitus, depression, anxiety), mechanism of injury (sports, non-sports), and date of injury were collected. Postoperative notes were reviewed to determine compliance. Patients completed the Foot & Ankle Ability Measure (FAAM)-Activities …

Impact Of Smartphone Usage On Children’S Horizontal Fusional Amplitudes, Jordan Hamburger, Judith Lavrich, Md, Kammi Gunton, Md

Phase 1

Introduction: Cell phone usage has increased in pediatric patients and little research has been done on its effects on patients’ fusional vergence amplitudes. We aim to study the impact of smartphone usage on healthy pediatric patients’ fusional vergence amplitudes and report findings that may lead to future eye problems.

Methods: This is a prospective randomized study. We are currently recruiting healthy patients between the ages of 8-17 years old with no ocular problems. Data collected include refractive error, ocular alignment in the distance and at near, divergence amplitudes at near and in distance, convergence amplitudes at near and in distance, …

Determining The Role Of Surgery In Diagnosis And Treatment Of Primary Cns Lymphoma, Tyler Fox, Michael Baldassari, Lohit Velagapudi, Karim Hafazalla, Christopher J. Farrell, Md, James J. Evans, Md, David W. Andrews, Md, Kevin Judy, Md, Donald Ye, Md

Phase 1

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare entity typically treated with a combination of chemotherapy and radiation. The role of surgery is controversial, and biopsy may be non-definitive or injurious. We review our series of stereotactic and excisional biopsy as well as surgical debulking of PCNSL to quantify overall risk and benefits.

Methods: Patients with biopsy-confirmed intracranial PCNSL were identified from a large singlecenter academic institution between 2012-2018. Preoperative factors and perioperative outcomes were retrospectively reviewed.

Results: A total of 61 cases of PCNSL were identified. Most patients presented with confusion (23.0%), weakness/paralysis (19.7%), and gait disturbance …

Outcomes In Knot Vs Knotless Surgery In Labrum Tears, Zachary Howell, Benjamin Hendy, Md

Phase 1

A Bankart lesion is a tear of the anterior and inferior glenoid labrum. The primary method of repairing this lesion is to sew the detached part back to the joint, however there is a relatively newer method of doing so that does not involve tying a knot in the joint which may cause less joint irritation. The question our research project attempted to answer was: How do the long-term outcomes associated with knotless Bankart labrum repairs compare with the knot repairs? A retrospective cohort study was done with Rothman Institute Bankart lesion patients from 2010-2016. Data was gathered over phone …

Effects Of (R,S)-Ketamine And (2r,6r)-Hydroxynorketamine: A Preclinical Study, Remington Rice

Theses and Dissertations

In 2017, 7.1% of US adults were diagnosed with depression, and 50% of patients received medication to treat their depression. Depression can cause severe interruptions in an individual's cognitive functioning and behaviors like sleeping, eating, working, and socializing. Unfortunately, approximately 40% of patients do not respond to treatment with monoaminergic medications (e.g. Prozac) and therapeutic effects may be delayed 2-8 weeks. Due to these therapeutic shortcomings, faster acting and more efficacious treatments are needed. Recent preclinical findings indicate potential for glutamatergic drugs like (R,S)-ketamine and (2R,6R) hydroxynorketamine to produce more rapid and longer-acting therapeutic effects. The antidepressant effectiveness of (R,S)-ketamine …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …