Translational Medical Research Commons^™

Parp1-Targeted Radiotherapies, Stephen Jannetti

Dissertations, Theses, and Capstone Projects

Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …

Mitochondrial Quality Control In Age-Related Pulmonary Fibrosis., Willy Roque, Karina Cuevas-Mora, Freddy Romero

Center for Translational Medicine Faculty Papers

Idiopathic pulmonary fibrosis (IPF) is age-related interstitial lung disease of unknown etiology. About 100,000 people in the U.S have IPF, with a 3-year median life expectancy post-diagnosis. The development of an effective treatment for pulmonary fibrosis will require an improved understanding of its molecular pathogenesis and the "normal" and "pathological' hallmarks of the aging lung. An important characteristic of the aging organism is its lowered capacity to adapt quickly to, and counteract, disturbances. While it is likely that DNA damage, chronic endoplasmic reticulum (ER) stress, and accumulation of heat shock proteins are capable of initiating tissue repair, recent studies point …

Effects Of Deceptive Footwear Condition On Subjective Comfort And Running Biomechanics, Zoe Y.S. Chan, Ivan P.H. Au, Janet H. Zhang-Lea, Reed Ferber, Gary Shum, Winko W. An, Roy T.H. Cheung

Human Physiology Faculty Scholarship

Comfort is a major criterion for footwear selection. Previous studies have suggested that physical properties were not enough to predict comfort and psychological factors could also affect the perception. To understand comfort, this study examined the effect of controlled shoe description and price cue on the perception of comfort. Furthermore, this study also examined the running biomechanics in response to footwear conditions of differing comfort. Fifteen runners completed treadmill running tests in two conditions: Shoe A and Shoe B. The same pair of neutral running shoes was used in both conditions, yet, Shoe B was described to be the “latest …

Opioid Tolerance Influences Outcomes After Lumbar Fusion In Patients With Degenerative Pathology, Noah Levy, Max Detweiler, Dhruv K.C. Goyal, Ariana Reyes, Alexander R. Vaccaro

Phase 1

Introduction: Extended opioid use prior to surgery has been implicated in poorer postoperative outcomes. However, it remains unclear if there is a significant difference in postoperative outcomes among preoperative opioid-naïve and opioid-tolerant patients who undergo lumbar spinal fusion. The purpose of this study was to determine the effect of preoperative opioid use on patient-reported outcome measures in patients undergoing lumbar spinal fusion.

Methods: This retrospective cohort analysis identified 260 patients who underwent lumbar spinal fusion at a high-volume, single institution. There were two cohorts: patients who were opioid-naïve (defined as total opioid consumption of ≤ 7 days in …

Prediction Of Neonatal Birthweight Associated With Maternal Obesity And Diabetes, Laura Gleason, Rebekah Mccurdy, Md, Mph

Phase 1

Introduction: To design a model that will predict neonatal birth weight within obese mothers by diabetic status.

Methods: A secondary data analysis of an RCT (NCT 02909582) was utilized to create a neonatal birth weight prediction model. Women (n=325) with a BMI > 35 kg/m2 from a tertiary academic institution, 2016 – 2019, were included to estimate the risk of large for gestational age (LGA) infants and neonatal birth weight based on maternal prepregnancy BMI and diabetic status. LGA was defined as an infant birth weight > 90th percentile. Analysis included Chi-square, t-test, multivariate logistic and linear regression.

Results: Mean birthweight did …

Understanding The Relationship Between Drug Overdose Death Rates And Socioeconomic Factors, William Duan, Dennis J. Hand

Phase 1

Drug-overdose deaths increased rapidly recently. What are the causes? We believe socioeconomical factors play critical roles. Secondary data analyses are done on the US population, using mortality-data files from the National Vital Statistics System. Deaths are grouped by race, age, sex, education and marital status. We believe that the percentage-of-total-death (PoTD) value, which equals to the number-of-overdose-deaths divided by the total-number-of-deaths in the corresponding group, more accurately reflect the severity of overdose-deaths. Analysis of 2017 data reveals that among all age groups, PoTD is highest in the age 25-34 group, with dramatic differences between white (PoTD 24%) and black (PoTD …

The Role Of Rassf5 On Cell Growth And Hippo Signaling In Rhabdomyosarcoma, Megan Garver, Lee Helman, Md, Katrina Slemmons, Phd

Phase 1

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Dysregulation of the Hippo pathway, a signaling cascade that regulates many biological processes, is associated with many human cancers. The goal of my project was to delete RASSF5, a regulator of the Hippo pathway, in RMS cells utilizing CRISPR/Cas9 and then to evaluate how the absence of RASSF5 affects RMS cell growth and Hippo signaling, with and without DNMTi Tx.

Methods: A lipofectamine transfection was performed in two different RMS cell lines, Rh30 & RD, in which two different CRIPSR/Cas9 vectors with RASSF5 guide RNA were introduced. …

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

Phase 1

RATIONALE: Discharging patients directly from ICUs is an increasingly common practice, largely due to decreased availability of ward beds. The purpose of this study was to describe the population and evaluate the outcomes of patients discharged directly from the MICU.

METHODS: We conducted a retrospective chart review of direct discharges to home from June 2018 to June 2019 from two MICUs. Patients were separated into two groups based on wait time (<24 hours or ≥ 24 hours) between ward transfer order and actual discharge. The primary outcome was 30-day hospital readmission. Risk was adjusted using Mortality Probability Model (MPM-III); ICU workload at admission and discharge was estimated using the nine equivalents of nursing manpower use score (NEMS). Patient characteristics were compared using t-test and Fisher exact or X².

RESULTS: There was no difference in severity-of-illness or admission NEMS between the two groups. Patients who waited <24 hours for discharge were more likely to be admitted from home. Patients who waited ≥24 hours prior to discharge had significantly longer mean hospital LOS compared to those who waited <24 hours (4.63 days vs. 2.65 days, p<0.001). There was no significant difference in 30-day readmission between patients who were discharged after waiting <24 hours vs. waiting ≥24 hours (p=0.70).

CONCLUSION: Patients who returned directly home from the MICU …

Treatment Of Persistent Air Leaks Using Endobronchial Valves, Michael Zimmerman, Cole Zingas, Achala Donuru, Scott W. Cowan, Nathaniel Evans Iii, Boyd Hehn

Phase 1

Introduction: Persistent air leaks (PAL) are from bronchopleural fistula resulting from communication between the bronchial tree and pleural space. Endobronchial valves (EBVs) are unidirectional valves placed bronchoscopically preventing airflow to the diseased lung lobe. For non-operable patients with PALs, EBVs offer a potential non-invasive treatment approach to stop air leak and allow lung healing. The purpose of this study is to retrospectively analyze EBV placement to treat non-operable adult patients with PALs.

Methods: We retrospectively analyzed all adult patients that underwent EBV placement for PAL treatment at our institution from January 2016 to June 2019. All patients failed conservative …

Late Complications Of Free Flaps In Head And Neck Microvascular Reconstruction, Swapna Vasudevan, Cory Bovenzi, Md

Phase 1

Introduction: Late free flap complications (LFFC) in head and neck reconstructive surgery occur over 72 hours postoperatively and result in flap loss in 97% of cases. Due to the rarity of LFFC, there is minimal research regarding risk factors for their development. Identifying risk factors for LFFC will result in improved monitoring of patients to prevent flap loss. This study aims to identify risk factors for the development of LFFC.

Methods: The target population of this retrospective cohort study was 116 patients who had undergone an Orbital Exenteration at Thomas Jefferson University Hospital (TJUH) and had LFFC. Data was …

Effects Of Corneal Transplant On Rates Of Retinal Detachment, Daniel S. Mackinnon, Zeba A. Syed, Md, Durga Borkar, Hannah Levin

Phase 1

Introduction: Corneal transplant remains the gold standard treatment for irreversible corneal damage. The purpose of this study is to evaluate retinal detachment rates and clinical outcomes after penetrating keratoplasty (PK) and endothelial keratoplasty (EK). We hypothesized that corneal transplants would increase the rate of RD.

Methods: This retrospective cohort study utilized corneal transplant data from all surgical visits from PK or EK between April 1, 2012 and August 31, 2018. Individual charts were reviewed from patients who had a subsequent retinal detachment. Incidence of retinal detachment following PK or EK was the main outcome measured.

Results: A total of …

Cardiovascular: Outcomes And Innovations Report, Maine Medical Center

Annual Reports

2020 Annual Report

Protocol For Ground Glass Opacity, Elissa Goldman

Phase 1

Rationale: Pure ground glass opacities (GGO), identified incidentally or on lung cancer screening, may indicate pre-invasive subtypes of lung adenocarcinoma. These neoplasms typically demonstrate indolent patterns of growth, and Fleischner Society guidelines recommend up to five years of serial imaging. Our aim was to determine the frequency of diagnosed lung adenocarcinoma arising from GGO detected beyond 5 years of CT surveillance.

Methods: We reviewed all pathologic diagnoses of lung adenocarcinoma (n=442) between 2016 and 2018 of a tertiary academic hospital and National Cancer Institute-designated cancer center to identify all cancers that arose from ground glass opacities detected on CT scan. …

Ain To Ulnar Motor Nerve Transfer Meta Analysis, Melanie Luikart, Asif M. Ilyas, Md

Phase 1

Background: There are currently few comprehensive studies of end-to-end and “supercharged” reverse end-to-side (SETS) anterior interosseous nerve (AIN) to ulnar nerve transfers for treatment of ulnar neuropathy. The authors performed a literature review existing published literature to evaluate the indications for, and utility of, AIN-ulnar nerve transfer as a treatment method and to inform future treatment decisions.

Methods: A literature review was performed based on the following inclusion criteria: inclusion of anterior interosseous nerve or AIN, ulnar nerve or ulnar motor nerve, transfer or nerve transfer, and outcome, motor, clinical, ulnar neuropathies, ulnar nerve paralysis, treatment or function. Exclusion criteria …

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 …

The Efficacy And Safety Profile Of Netarsudil 0.02% In Glaucoma Treatment: Real-World Outcomes, Eric Shiuey, Ms, Melih Ustaoglu, Md, Carina Sanvicente, Md, Reza Razeghinejad, Md, L. Jay Katz, Md, Jonathan Myers, Md, Daniel Lee, Md

Phase 1

Introduction: More effective glaucoma medications are necessary as medication intolerance and non-adherence remain problematic. Netarsudil is a newly FDA-approved Rho kinase inhibitor. We hypothesize that netarsudil will safely reduce intraocular pressure (IOP) compared to baseline even while other glaucoma medications are used.

Methods: This retrospective observational study was conducted on glaucoma patients seen at the Wills Eye Hospital Glaucoma Service who received netarsudil 0.02% between March and September of 2018. Intraocular pressure (IOP, via Goldmann applanation tonometry) and best corrected visual acuity (BCVA, via Snellen visual acuity charts) comparisons between baseline and 1- and 3-month follow-up visits were performed …

Conjunctival Melanoma: Features Based On The Fitzpatrick Skin Type (Fst) In 540 Patients At A Single Ocular Oncology Center, Sunihidi Ramesh, Antonio Yaghy, Lauren A. Dalvin, Sara E. Lally, Jerry A. Shields, Carol L. Shields

Phase 1

Background: The Fitzpatrick skin type (FST) is a classification system for skin pigmentation that has been used to stratify risk for cutaneous melanoma; however, it has not yet been explored in the context of conjunctival melanoma. Herein, we examine FST and its association with the clinical features of conjunctival melanoma.

Methods: A retrospective review was conducted on 540 medical records of patients with pathologic diagnosis of conjunctival melanoma. The patients were categorized according to the FST classification based on their external facial photographs at presentation. This includes: Type I (white skin color), Type II (fair skin color), Type III (average …

Middle Fossa Extension Of Posterior Fossa Meningiomas Is Associated With Poorer Clinical Outcomes, David Morgan, Donald Y. Ye, Md, Michael P. Baldassari, Omaditya Khanna, Md, Aria Mahtabfar, Md, Tyler Henry, Haley Wendt, David W. Andrews, Md, Christopher J. Farrell, Md, James J. Evans, Md, Kevin D. Judy, Md

Phase 1

Introduction: Progression of posterior fossa meningiomas (PFMs) can lead to extension into the middle cranial fossa. Pre-operative imaging allows for quantification of middle fossa extension (MFE). We aimed to determine the clinical impact of MFE on surgical and clinical outcomes during resection of PFMs.

Methods: Craniotomies for meningiomas performed at a large single center academic institution from January 2012 to December 2018 were identified. Preoperative MRI and CT imaging was reviewed to determine the presence of MFE of posterior fossa meningiomas and correlated to post-operative outcomes.

Results: 65 PFMs were identified and mean follow-up was 28.8 ± 20.1 months. 13/65 …

Early Perioperative Fluid Benchmarking To Predict Pancreaticoduodenectomy (Pd) Outcomes, David Moskal, Carrie D. Walsh, Sofia Duque, Charles Yeo, Md, Facs, Harish Lavu, Md, Facs

Phase 1

Introduction: PD is a complex operation associated with a marked systemic inflammatory response and significant fluid shifts. Establishing a benchmark for ideal perioperative fluid management is critical to optimising PD patient recovery.

Methods: In this retrospective study, we evaluated perioperative fluid data for patients undergoing PD. We compared an optimal benchmark group who were discharged home by postoperative day five (≤5day) to a group of patients with an in hospital recovery greater than ten days (≥10day).

Results: Seventy-six patients who underwent PD between June 2015 and November 2016 were evaluated. The ≤5day group had a significantly lower intraoperative fluid administration …

Meta-Analysis Of Repair Techniques For Mixed Nerve Damage, Grant Jones, Zachary J. Herman, Asif Ilyas

Phase 1

BACKGROUND: Injuries to the upper extremity are common and can occur with trauma, surgery, or compression. Particularly, injuries that result in complete transection often require surgical intervention in attempt to restore function and quality of life. Classically, nerve autografts have been used as the gold standard to repair these peripheral lesions. An alternative to the autologous nerve graft is the use of the processed nerve allograft. limited research exists in comparing sensory and motor outcomes of allograft nerve repair in the upper extremity with data for autograft repair. In this systematic review and meta-analysis, we set out to cumulate results …