Diseases Commons^™

Pre-Hospital And Post-Hospital Quality Of Care In Traumatic Spinal Column And Cord Injuries In Iran, Arman Zeinaddini-Meymand, Vali Baigi, Mohammad Mehdi Mousavi-Nasab, Sina Shool, Mohsen Sadeghi-Naini, Zahra Azadmanjir, Seyed Behnam Jazayeri, Samuel Berchi Kankam, Mohammad Dashtkoohi, Aidin Shakeri, Esmail Fakharian, Leila Kouchakinejad-Eramsadati, Habibollah Pirnejad, Homayoun Sadeghi-Bazargani, Laleh Bagheri, Yasaman Pourandish, Malihe Amiri, Ahmad Pour-Rashidi, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

STUDY DESIGN: A retrospective study.

OBJECTIVES: The quality of care (QoC) for spinal column/cord injury patients is a major health care concern. This study aimed to implement the QoC assessment tool (QoCAT) in the National Spinal Cord/Column Injury Registry of Iran (NSCIR-IR) to define the current state of pre- and post-hospital QoC of individuals with Traumatic Spinal Column and Spinal Cord Injuries (TSC/SCIs).

METHODS: The QoCAT, previously developed by our team to measure the QoC in patients with TSC/SCIs, was implemented in the NSCIR-IR. The pre-hospital QoC was evaluated through a retrospective analysis of NSCIR-IR registry data. Telephone interviews and …

Evaluating Dysphagia Duration And Severity After Acdf In Patients With Underlying Dysphagia - A Prospective, Multicenter Study, Aditya Mazmudar, Taylor Paziuk, Khoa Tran, Tyler Henry, Samuel Oh, Caroline Purtill, Daniel Habbal, Goutham Yalla, Quinlin Harrill, Brandon Sherrod, Erica Bisson, Darrel Brodke, Christopher Kepler, Gregory Schroeder, Alex Vaccaro, Alan Hilibrand, Jeffrey Rihn

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Prospective Cohort Study.

OBJECTIVES: The purpose of this study was to prospectively evaluate the impact of preoperative dysphagia on the postoperative incidence and severity of dysphagia in patients undergoing ACDF at multiple institutions.

METHODS: After IRB approval, patients over 18 years of age who underwent an elective ACDF for degenerative conditions were prospectively enrolled at two academic centers from 2018 to 2021. Preoperative dysphagia was self-reported by patients through a pre-operative questionnaire on a binary basis. Patients completed dysphagia surveys (Bazaz, Dysphagia Short Questionnaire, 10-item Eating Assessment Tool) to assess dysphagia severity during their preoperative visit, and these …

An Update In Complication Rates Associated With Anterior Lumbar Surgery: A Systematic Review And Meta-Analysis, Tariq Z Issa, Teeto Ezeonu, Mason Sellig, Chester J Donnally, Rajkishen Narayanan, Brian A Karamian, Parthik D Patel, Srikanth N Divi, William A Robinson, Kartik Shenoy, Christopher K Kepler, Alexander R Vaccaro, Jose A Canseco

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Systematic Review and meta-analysis.

OBJECTIVE: To conduct an updated systematic review and meta-analysis of complications associated with different anterior fusion techniques/approaches and adjuvant resources (i.e., computed tomography angiography (CTA), rhBMP-2, and access surgeons).

METHODS: A systematic review was conducted from 1/1/2014-4/1/2024 for studies evaluating the incidence of complications associated with anterior lumbar procedures. Comparisons of complications were made between surgical approach, use of CTA, rhBMP-2, and access surgeons. Meta-analyses were conducted using a generalized linear mixed model.

RESULTS: 54 studies were included in the final analysis with 8066 patients and an average follow-up of 31.2 months. The overall …

Spetzler-Martin Grade I And Ii Cerebral Arteriovenous Malformations: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery In Adult Patients, Salem Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Adam Dmytriw, Hamza Adel Salim, Basel Musmar, Kareem El Naamani, Christopher Ogilvy, Douglas Kondziolka, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Ufuk Erginoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev Sen, Omar Alwakaa, Christoph Griessenauer, Pascal Jabbour, Stavropoula Tjoumakaris, Jan-Karl Burkhardt, Robert Starke, Mustafa Baskaya, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng Chen, Spiros Blackburn, Mark Dannenbaum, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman Patel, Hugo Cuellar, Michael Lawton, Jacques Morcos, Bharat Guthikonda, Jason Sheehan

Department of Neurosurgery Faculty Papers

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability …

Increasing Risk Of Postlung Transplant Hospitalizations For Infection: An Analysis Of Recent Trends, Shi Nan Feng, Armaan F. Akbar, Alice L. Zhou, Andrew Kalra, Sean Agbor-Enoh, Christian A. Merlo, Errol L. Bush

SKMC Student Presentations and Publications

BACKGROUND: Despite advancements in lung transplantation (LT), infection remains a major cause of morbidity and mortality following LT. We examined trends in hospitalizations for infection in the first year after LT.

METHODS: We identified adult LT recipients in the United States (March 1, 2018-March 9, 2023) using the Organ Procurement and Transplantation Network database. We categorized transplants into 3 eras to account for the Composite Allocation Score allocation policy change and coronavirus disease 2019: March 2018 to March 2020, March 2020 to March 2022, and March 2022 to March 9, 2023. One-year post-LT survival was compared using Kaplan-Meier survival analysis …

A Review Of Gut Failure As A Cause And Consequence Of Critical Illness, Danielle E. Soranno, Craig M. Coopersmith, Jessica F. Brinkworth, Faith N. F. Factora, Julia H. Muntean, Monty G. Mythen, Jacob Raphael, Andrew D. Shaw, Vidula Vachharajani, Jeannette S. Messer

Department of Anesthesiology Faculty Papers

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of …

Ultrasound-Triggered Release Of Vancomycin From A Novel Spinal Device: Antibiotic Release And Efficacy In Vivo, Lauren J. Delaney, Priscilla Machado, Ji-Bin Liu, Rachel Evans, Asia Winslow, Neil Zhao, Christopher K. Kepler, Rajkishen Narayanan, Teeto Ezeonu, Viren Soni, Gagan Kaushal, Rachel Hilliard, Thomas P. Schaer, Noreen J. Hickok, Flemming Forsberg

Department of Orthopaedic Surgery Faculty Papers

Post-surgical spinal infection occurs in up to 20 % of patients, despite aggressive peri-operative antibiotic treatments. To improve prophylaxis, we have designed and evaluated an ultrasound-activated prophylactic antibiotic release system to combat post-surgical bacterial survival. Polylactic acid (PLA) clips (1 cm³) were 3D-printed with an interior reservoir (0.8 cm³) for carrying drug payload, specifically vancomycin (VAN). Under IACUC approval, clips were surgically implanted into the spines of sheep (n = 9) and swine (n = 2) by removing the spinous process at several levels of the lumbar spine. In the sheep, clips were insonated and the …

Assessing The Effects Of Long-Covid On Mental Health In The United States: A Population Based Study, Anusua Datta

School of Business Faculty Papers

BACKGROUND: While most individuals recover fully from COVID-19, a significant proportion of survivors experience prolonged symptoms lasting three months or more, a condition commonly referred to as long-COVID. Long-COVID conditions have been associated with reduced quality of life. By utilizing a nationally representative sample of nearly a million Americans, this study provides insights into the prevalence and impact of long-COVID on anxiety and depression in the U.S.

METHODS: We utilize the Household Pulse Survey data, which provides the first population-based sample on the prevalence of long-COVID, beginning with its June 2022 wave. This survey also includes questions on respondents' mental …

Clinical Variability In Presentation And Management Of Quadricuspid Aortic Valve: A Case Series, Douglas Corsi, Brooke Kelly, Nikta Nair, Meiqi Luo, Brian Osler, Sung-Hae Cho, Praveen Mehrotra, David H Wiener, Drew Johnson

Division of Cardiology Faculty Papers

• Rare presentation of three QAV cases with varied clinical manifestations is reported. • Multimodal imaging is crucial for accurate QAV diagnosis and classification. • QAV is often associated with aortic regurgitation requiring intervention. • Surgical repair is preferred over replacement in suitable patients with QAV. • Long-term follow-up is essential for patients with QAV, even if asymptomatic.

Utilization Of Suprathel® In Delayed Surgical Management Of Toxic Epidermal Necrolysis (Ten): A Case Report, Isabella Lipkin, Michelle Hughes, W. B. Hughes Md

Jefferson Hospital Staff Papers and Presentations

Given the lack of established practice guidelines for the management of cutaneous symptoms associated with toxic epidermal necrolysis, treatments range from various dressings to skin substitutes. The following report details a case of a 21-year-old male patient with this diagnosis who presented nine days after rash eruption from an outside hospital with no signs of healing. The patient was then successfully managed surgically eleven days after symptom onset with debridement of epidermal blisters and placement of Suprathel®. To our knowledge, this publication is the first to describe the potential of this synthetic skin substitute in promoting epidermal regeneration for delayed …

Time To Initiation Of Antiresorptive Agents In Multiple Myeloma To Reduce Skeletal Related Events, Amman Bhasin, Adam Binder, Leland Damron, Amry Majeed, Adam Barsouk, Kelly Hughes, Thomas Jefferson University, Abdullateef O. Abdulkareem, Tingting Zhan, Divya Polu, Sai Gundepalli, Srinivas Devarakonda

Kimmel Cancer Center Faculty Papers

Purpose: Current treatment guidelines strongly support the use of antiresorptive therapy in patients with newly diagnosed multiple myeloma (NDMM) with the goal of preventing skeletal related events (SRE). Despite these concrete, data-driven recommendations, the impact of delays in antiresorptive initiation in NDMM patients is understudied. Through a multicenter retrospective study, we examined the impact of delays in antiresorptive initiation on the rates of SREs. We furthered our exploration of this topic in a separate retrospective analysis with a focus on reasons for delays in antiresorptive therapy initiation. Methods: Electronic health records from two large academic institutions were used to identify …

The Unfolding Story Of Protein Misfolding Causing Alzheimer Disease In Recipients Of Human Pituitary Growth Hormone, Evan G. Graber, Sayed M. Hadi Hosseini, Darrell M. Wilson, Alan D. Rogol

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are …

Self Supervised Artificial Intelligence Predicts Poor Outcome From Primary Cutaneous Squamous Cell Carcinoma At Diagnosis, Nicolas Coudray, Michelle C. Juarez, Maressa C. Criscito, Adalberto Claudio Quiros, Reason Wilken, Stephanie R. Jackson Cullison, Mary L. Stevenson, Nicole A. Doudican, Ke Yuan, Jamie D. Aquino, Daniel M. Klufas, Jeffrey P. North, Siegrid S. Yu, Fadi Murad, Emily Ruiz, Chrysalyne D. Schmults, Cristian D. Cardona Machado, Javier Cañueto, Anirudh Choudhary, Alysia N. Hughes, Alyssa Stockard, Zachary Leibovit-Reiben, Aaron R. Mangold, Aristotelis Tsirigos, John A. Carucci

Department of Dermatology and Cutaneous Biology Faculty Papers

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. Using whole-slide images (WSI) from 163 patients from 3 institutions, we developed a self supervised deep-learning model to predict poor outcomes in cSCC patients from histopathological features at initial diagnosis, and validated it using WSI from 563 patients, collected from two other academic institutions. For disease-free survival prediction, the model attained a concordance index of …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

Hidradenitis Suppurativa Is Associated With An Increased Risk Of Adverse Cardiac Events And All-Cause Mortality, Thomas Z. Rohan, Ramsay Hafer, Teresa Duong, Rishob Dasgupta, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Hidradenitis suppurativa (HS) has been previously associated with greater rates of major adverse cardiac events (MACEs) compared to the general population. This study aims to better elucidate the association between HS, MACEs, and other cardiovascular diseases. Methods: We utilized TriNetX, a global database of electronic health records, to conduct a retrospective cohort study. HS patients were matched on demographic and cardiovascular disease risk factors to both healthy and psoriasis groups as controls. Results: After adjusting for cardiovascular disease risk factors, HS patients had a relative risk (RR) (95% CI) of 2.06 (1.83-2.32) for myocardial infarction, 1.62 …

Axillo-Caval Extra-Anatomic Venous Bypass Creation Via Direct Percutaneous Puncture Of The Superior Vena Cava, Stephan S. Leung, Patrick Lee, Anthony N. Hage, Robert W. Ford

Department of Radiology Faculty Papers

No abstract provided.

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam Jaber, Carin Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal Gandhi, Keith Pereira, Jay Giri, Sameer Khandhar, Khawaja Afzal Ammar, David Lasorda, Brian Stegman, Lucas Busch, David Dexter, Ezana Azene, Nikhil Daga, Fakhir Elmasri, Chandra Kunavarapu, Mark Rea, Joseph Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason Smith, Thomas Tamlyn, Gabriel Hernandez, Parth Rali, Torrey Schmidt, Jeffrey Bruckel, Juan Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian Bergmark, Bhavraj Khalsa, David Zlotnick, Jordan Castle, David O'Connor, C. Michael Gibson

Department of Radiology Faculty Papers

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

Exploring Access To Care In Zimbabwe Using The 3-Delay Model, Katerina Green, Naboth Matinhira, Amiti Jain, Tissiana Vallecillo, Priya Arya, Estephania Candelo, Munyaradzi Katiro, Tafadzwa Nyamurowa, Dontre' Douse, Joshua Wiedermann

SKMC Student Presentations and Publications

OBJECTIVES: We aim to identify the diversity of barriers to care for otolaryngology-head and neck surgery patients in Harare, Zimbabwe.

METHODS: Interviews were conducted at four general otolaryngology clinics in Harare in October 2022.The patient population included children and adults presenting to either government or private clinics. Via interpreter, six standardized questions were discussed with each patient. Survey responses were used to categorize patients into one or more of three types of delays: (1) deciding to seek care, (2) reaching the appropriate healthcare facility, and (3) receiving adequate care after reaching that facility.

RESULTS: Forty-six patients participated in this survey. …

Hypoalbuminemia And Postoperative Outcomes Following Major Salivary Gland Resection, Praneet C. Kaki, Aman M. Patel, Jason A. Brant, Steven B. Cannady, Karthik Rajasekaran, Robert M. Brody, Ryan M. Carey

SKMC Student Presentations and Publications

OBJECTIVE: Hypoalbuminemia (HA) is a proxy for malnutrition that has been associated with postoperative complications in several surgical subspecialties. This study investigates the association between pre-operative HA and complications following major salivary gland (MSG) resection.

METHODS: Patients undergoing outpatient, elective MSG resection were extracted from the 2005 to 2020 National Surgical Quality Improvement Program database. Demographics and comorbidities were compared between HA (preoperative serum albumin < 3.5 g/dL) and non-HA cohorts. To determine associations between albumin status and postoperative complications, univariate and multivariable binary logistic regression analyses were performed.

RESULTS: A total of 5774 patients undergoing MSG resection were included, of which 321 (5.6%) had preoperative HA. HA was associated with older age on univariate analysis (65.2 vs. 60.2 years,

CONCLUSION: Preoperative HA may …

Palovarotene In Fibrodysplasia Ossificans Progressiva: Review And Perspective, Vincent Verheij, Robert Diecidue, Esmée Botman, Joseph Harrington, Nobuhiko Haga, Alberto Hidalgo-Bravo, Patricia Delai, Vrisha Madhuri, Mona Al Mukaddam, Keqin Zhang, Tae-Joon Cho, Rolf Morhart, Richard Keen, Carmen De Cunto, Clive Friedman, Zvi Grunwald, Michael Zasloff, J. Coen Netelenbos, Edward Hsiao, Frederick Kaplan, Robert Pignolo, Christiaan Scott, Elisabeth Marelise Eekhoff

Department of Oral and Maxillofacial Surgery Faculty Papers

INTRODUCTION: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A., Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

AREAS COVERED: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

EXPERT OPINION: While post hoc analyses …

Nrf2/Cyclooxygenase 2 Signaling In Cr(Vi)-Induced Carcinogenesis, Lei Zhao, Yi-Fang Wang, Andrea Adamcakova-Dodd, Peter Thorne, Ranakul Islam, Ke Jian Liu, Fei Chen, Jia Luo, Ling-Zhi Liu

Kimmel Cancer Center Faculty Papers

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upre- gulated in Cr(VI)-exposed lung tissues, as well as in the …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree Mcafee, Pamela Hull, Amy Leader, Christopher Mcnair

Kimmel Cancer Center Faculty Papers

The National Cancer Institute's (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …

Acute Carpal Tunnel Syndrome Secondary To Handcuffs Necessitating Emergency Orthopedic Consultation And Operative Intervention, Fabian Jano, Kelly Mackenzie, Vivek Biololikar, David Goldberger, Andrei Tuluca

Department of Emergency Medicine Faculty Papers

We present a case of acute carpal tunnel syndrome secondary to tight handcuffs in a detained patient. The severity of the motor and sensory deficits prompted consultation with orthopedic specialists and admission for an observation period with ultimate emergency operative intervention. Handcuff neuropathies are well documented in the literature, mainly involving the superficial branch of the radial nerve, which has strict sensory input into the dorsum of the hand. Less common median nerve neuropathies have also been documented following handcuff injury; however, none have required emergency intervention. We aim to highlight this unusual presentation and the emergency nature of the …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Characterizing Prodrome (Premonitory Phase) In Migraine: Results From The Prodrome Trial Screening Period, Todd Schwedt, Richard Lipton, Peter Goadsby, Chia-Chun Chiang, Brad Klein, Cory Hussar, Chengcheng Liu, Sung Yun Yu, Michelle Finnegan, Joel Trugman

College of Nursing Faculty Papers & Presentations

BACKGROUND AND OBJECTIVE: Limited data are available describing the frequency, severity, and consistency of prodromal symptoms followed by headache. This analysis of the PRODROME trial screening period characterized prodromal symptoms in people with migraine, including the most common symptoms and their severity, and the frequency and consistency with which prodromal symptoms were followed by headache.

METHODS: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial conducted in the United States that enrolled adults with 2-8 migraine attacks per month who stated they could identify prodromal symptoms that were reliably followed by a headache. The trial included a 60-day screening period …

Patient-Reported Outcomes: Comparing Functional Avoidance And Standard Thoracic Radiation Therapy In Lung Cancer, Spencer Poiset, Joseph Lombardo, Edward Castillo, Richard Castillo, Bernard Jones, Moyed Miften, Brian Kavanagh, Adam Dicker, Cullen Boyle, Nicole Simone, Benjamin Movsas, Inga Grills, Chad Rusthoven, Yevgeniy Vinogradskiy, Lydia Wilson

Department of Radiation Oncology Faculty Papers

PURPOSE: Novel methods generate functional images using image processing techniques combined with four-dimensional computed tomography (4DCT) data (4DCT-ventilation). 4DCT-ventilation was implemented in a phase II, multicenter functional avoidance clinical trial. The work compares functional avoidance patient-reported outcomes (PROs) against historical standards.

METHODS: Patients with locally advanced lung cancer undergoing curative-intent chemoradiation were accrued. 4DCT-ventilation imaging was generated and functional avoidance treatment plans created reduced dose to functional lung. PRO instruments included Functional Assessment of Cancer Therapy Lung questionnaire and accompanying subscales (including the Trial Outcome Index [TOI]), EuroQol-5 Dimension (EQ-5D), and EQ-Visual Analog Scale (EQ-VAS). The average change from baseline …