Medicine and Health Sciences Commons^™

Isolated Abducens Nerve Palsy: A Rare Manifestation Of Recurrent Extramedullary Myeloma, Neal Joshi, Joy Li, Ajit Karambelkar, Payton Boere

Jefferson Hospital Staff Papers and Presentations

Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas may manifest in central nervous system involvement as cranial nerve palsies. Cranial nerve six palsy is the most common in cases of malignancy. However, isolated abducens palsy presenting as multiple myeloma recurrence is very uncommon. Here, we detail two cases in which intracranial plasmacytoma lesions were present within the region of the Dorello canal, resulting in acute isolated unilateral diplopia from disease recurrence in the absence of systemic marrow involvement.

Prognostic Properties Of Kras Gene Mutation Subtypes In Resected Pancreatic Cancer, Faria Nusrat, Eliyahu Gorgov, Md, Wilbur Bowne, Md, Obehioye Isesele, Akshay Khanna, Harish Lavu, Md, Aditi Jain, Phd, Charles J. Yeo, Md, Avinoam Nevler, Md

Alpha Omega Alpha Research Symposium Posters

Introduction

• Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and therapy-resistant cancer with an overall 5-year survival rate of almost 12%, making it among the most lethal of all major cancers.¹
• PDAC has a distinct genomic profile, with somatic KRAS protooncogene mutations in ~90% of cases.^2,3
• Current literature has not reached a consensus on disease prognosis based on KRAS mutation subtype.^2-5

Recommendations From People Who Use Drugs In Philadelphia, Pa About Structuring Point-Of-Care Drug Checking, Megan K. Reed, Elias Borne, Tracy Esteves Camacho, Morgan Kelly, Kristin L. Rising

Department of Emergency Medicine Faculty Papers

Background

Adulterants, such as fentanyl and xylazine, among others, are present in a high percentage of the illicit drug supply, increasing the risk for overdose and other adverse health events among people who use drugs (PWUD). Point-of-care drug checking identifes components of a drug sample and delivers results consumers. To successfully meet the diverse needs of PWUD, more information is needed about the utility of drug checking, motivations for using services contextualized in broader comments on the drug supply, hypothesized actions to be taken after receiving drug checking results, and the ideal structure of a program.

Methods

In December 2021, …

Rates Of Reoperation In Duane Retraction Syndrome, Han Woong Lim, Bryce Hwang, Cyril Archambault, Scott Lambert

Wills Eye Hospital Papers

PURPOSE: To investigate the types of strabismus surgeries performed and the reoperation rate in patients with Duane retraction syndrome (DRS).

DESIGN: Retrospective cohort analysis.

PARTICIPANTS: An insurance claims data set was used to identify patients diagnosed with DRS between 2007 and 2021.

METHODS: We recorded the type of strabismus surgery performed and the timing and frequency of reoperations. The hazard ratios (HRs) for reoperation were estimated according to the surgical methods using Cox regression analysis.

RESULTS: Of the 9435 patients diagnosed with DRS, 1023 (10.8%) underwent ≥ 1 strabismus operation. The median age at surgery was 5.0 years, and patients …

Social And Psychosocial Determinants Of Racial And Ethnic Differences In Cardiovascular Health: The Masala And Mesa Studies, Nilay S. Shah, Xiaoning Huang, Lucia C. Petito, Michael P. Bancks, Alka M. Kanaya, Sameera Talegawkar, Saaniya Farhan, Mercedes R. Carnethon, Donald M. Lloyd-Jones, Norrina B. Allen, Namratha R. Kandula, Sadiya S. Khan

Student Papers, Posters & Projects

BACKGROUND: Social and psychosocial determinants are associated with cardiovascular health (CVH).

OBJECTIVES: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH.

METHODS: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants.

RESULTS: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 …

Echocardiographic Parameters Associated With Less Reverse Left Ventricular Remodeling After Transcatheter Aortic Valve Implant In Subjects With Prosthesis Patient Mismatch, Andrew C. Peters, Fei Fei Gong, Ashvita Ramesh, Adin Andrei, Madeline Jankowski, Eric Cantey, Vincent Chen, James D. Thomas, James D. Flaherty, S. Christopher Malaisrie, Kameswari Maganti

Division of Cardiology Faculty Papers

BACKGROUND: Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration.

METHODS: We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1 year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with …

Circulating Metabolic Profile In Idiopathic Pulmonary Fibrosis: Data From The Ipf-Pro Registry, Ross Summer, Jamie Todd, Megan Neely, L. Jason Lobo, Andrew Namen, L. Kristin Newby, Shirin Shafazand, Sally Suliman, Christian Hesslinger, Sascha Keller, Thomas Leonard, Scott M Palmer, Olga Ilkayeva, Michael Muehlbauer, Christopher Newgard, Jesse Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF.

METHODS: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF …

Nur77 Mitigates Endothelial Dysfunction Through Activation Of Both Nitric Oxide Production And Anti-Oxidant Pathways, Lin Lu, Soohwa Jang, Jiaqi Zhu, Qing Qin, Lijun Sun, Jianxin Sun

Center for Translational Medicine Faculty Papers

BACKGROUND: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved.

METHODS: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot …

Long-Term Surgical Outcomes Of Glaucoma Drainage Implants In Eyes With Preoperative Intraocular Pressure Less Than 19 Mmhg, Shahin Hallaj, Jae-Chiang Wong, Lauren E. Hock, Natasha Nayak Kolomeyer, Aakriti G. Shukla, Michael J. Pro, Marlene R. Moster, Jonathan S. Myers, Reza Razeghinejad, Daniel Lee

Wills Eye Hospital Papers

BACKGROUND: This retrospective review reports on patients who underwent glaucoma drainage implant (GDI) surgery and had baseline intraocular pressure (IOP) of ≤18 mmHg with at least one year of follow-up.

METHODS: Clinical data of 67 eyes of 67 patients were collected from patients' charts, and the outcomes of GDI were evaluated until 7 years. GDI failure was defined as IOP reduction of less than 20% from the baseline at two consecutive visits three months after surgery, decline to no light perception, or if additional glaucoma surgery was performed.

RESULTS: The average age was 65.9 ± 13.2 years. Most cases were …

Early Immersion In Team-Based Event Review: Experiential Patient Safety Education For Pgy 1 Internal Medicine Residents, Michelle Perkons, Alexis Wickersham, Sonia Bharel, Timothy Kuchera, Rebecca Jaffe

Department of Medicine Faculty Papers

INTRODUCTION: In recent years, there has been a national push to incorporate high-fidelity quality improvement and patient safety (QIPS) education into physician training programs. In fact, integration of robust patient safety education became an Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirement for residency programs in 2017. We developed a curriculum to not only fulfill the ACGME's requirement but also provide PGY 1 internal medicine residents with the skills needed to become active participants in ongoing patient safety work throughout their training and careers.

METHODS: Our patient safety curriculum was woven into residents' existing protected educational time and …

Patient And Caregiver Perceptions Of The Possibility Of Home Blood Transfusions, Adam F. Binder, Alavi Hossain, Riyana Doshi, Angelica Vivero, Karla Martin Gonzalez, Alexzandra Gentsch, Lindsay Wilde, Kristin L. Rising

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with hematologic malignancies (HM) often develop transfusion dependence. The patient and caregiver burdens associated with the need for frequent transfusions are high. Home blood transfusions has the potential to reduce these burdens, but is not widely practiced in the United States. We designed a qualitative study to evaluate the patient and caregiver perceptions of the potential for a home blood transfusion program.

STUDY DESIGN AND METHODS: Eligible patients included Adult (≥18 years) patients who were English speaking and met the definition for transfusion dependence within 3 months of study enrollment. We identified and interviewed eligible participants (patients and …

Post-Capillary Pulmonary Hypertension: Clinical Review, Joshua Riley, James Fradin, Douglas Russ, Eric Warner, Yevgeniy Brailovsky, Indranee Rajapreyar

Department of Medicine Faculty Papers

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary …

Microglia-Derived Exosomes Modulate Myelin Regeneration Via Mir-615-5p/Myrf Axis, Xiao-Yu Ji, Yu-Xin Guo, Li-Bin Wang, Wen-Cheng Wu, Jia-Qi Wang, Jin He, Rui Gao, Javad Rasouli, Meng-Yuan Gao, Zhen-Hai Wang, Dan Xiao, Wei-Feng Zhang, Bogoljub Ciric, Yuan Zhang, Xing Li

Department of Neurology Faculty Papers

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to …

A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …

The Impact Of Chronic Comorbidities On Outcomes In Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Saqib H. Baig, Erika J. Yoo

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF).

METHODS: This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression.

RESULTS: Out of …

Performance Of Automated Machine Learning In Predicting Outcomes Of Pneumatic Retinopexy, Arina Nisanova, Arefeh Yavary, Jordan Deaner, Ferhina Ali, Priyanka Gogte, Richard Kaplan, Kevin Chen, Eric Nudleman, Dilraj Grewal, Meenakashi Gupta, Jeremy Wolfe, Michael Klufas, Glenn Yiu, Iman Soltani, Parisa Emami-Naeini

Wills Eye Hospital Papers

PURPOSE: Automated machine learning (AutoML) has emerged as a novel tool for medical professionals lacking coding experience, enabling them to develop predictive models for treatment outcomes. This study evaluated the performance of AutoML tools in developing models predicting the success of pneumatic retinopexy (PR) in treatment of rhegmatogenous retinal detachment (RRD). These models were then compared with custom models created by machine learning (ML) experts.

DESIGN: Retrospective multicenter study.

PARTICIPANTS: Five hundred and thirty nine consecutive patients with primary RRD that underwent PR by a vitreoretinal fellow at 6 training hospitals between 2002 and 2022.

METHODS: We used 2 AutoML …

Microsurgical Clipping Of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation Of Perioperative Outcomes, Jennifer Sauvigny, Richard Drexler, Tobias Pantel, Franz Ricklefs, Joshua Catapano, John Wanebo, Michael Lawton, Aminaa Sanchin, Nils Hecht, Peter Vajkoczy, Kunal Raygor, Daniel Tonetti, Adib Abla, Kareem El Naamani, Stavropoula Tjoumakaris, Pascal Jabbour, Brian Jankowitz, Mohamed Salem, Jan-Karl Burkhardt, Arthur Wagner, Maria Wostrack, Jens Gempt, Bernhard Meyer, Michael Gaub, Justin Mascitelli, Philippe Dodier, Gerhard Bavinzski, Karl Roessler, Nico Stroh, Matthias Gmeiner, Andreas Gruber, Eberval Figueiredo, Antonio Carlos Samaia Da Silva Coelho, Anatoliy Bervitskiy, Egor Anisimov, Jamil Rzaev, Harald Krenzlin, Naureen Keric, Florian Ringel, Dougho Park, Mun-Chul Kim, Eleonora Marcati, Marco Cenzato, Linda Krause, Manfred Westphal, Lasse Dührsen, Thomas Sauvigny

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms.

METHODS: Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on …

Long-Term Open-Label Vebicorvir For Chronic Hbv Infection: Safety And Off-Treatment Responses, Man-Fung Yuen, Scott Fung, Xiaoli Ma, Tuan Nguyen, Tarek Hassanein, Hie-Won Hann, Magdy Elkhashab, Ronald Nahass, James Park, Ira Jacobson, Walid Ayoub, Steven-Huy Han, Edward Gane, Katie Zomorodi, Ran Yan, Julie Ma, Steven Knox, Luisa Stamm, Maurizio Bonacini, Frank Weilert, Alnoor Ramji, Michael Bennett, Natarajan Ravendhran, Sing Chan, Douglas Dieterich, Paul Yien Kwo, Eugene Schiff, Ho Bae, Jacob Lalezari, Kosh Agarwal, Mark Sulkowski

Department of Medicine Faculty Papers

BACKGROUND & AIMS: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs).

METHODS: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR …

Impact Of Left Ventricular Assist Devices On 30-Day Readmission And Outcomes In Non-Variceal Upper Gastrointestinal Bleeding: A Nationwide Analysis, Umer Farooq, Zahid Ijaz Tarar, Adnan Malik, Muhammad Kashif Amin, Mustafa Gandhi, Moosa Tarar, Faisal Kamal

Division of Gastroenterology and Hepatology Faculty Papers

INTRODUCTION: Bleeding, especially non-variceal upper gastrointestinal bleeding (NVUGIB), remains the most common cause of readmission in left ventricular assist device (LVAD) patients. Any readmission after NVUGIB carries a worse prognosis.

AIM: To compare readmission outcomes in NVUGIB patients with and without LVAD.

MATERIAL AND METHODS: We identified adult NVUGIB patients using the National Readmission Database 2018 employing International Classification of Diseases, Tenth Revision (ICD-10) codes. The patients were grouped based on LVAD history. Proportions were compared using the Fisher exact test, and multivariate Cox proportional regression analysis was used to compute adjusted

RESULTS: The analysis included 322,342 NVUGIB patients, 1403 …

Deep Learning-Based Multimodality Classification Of Chronic Mild Traumatic Brain Injury Using Resting-State Functional Mri And Pet Imaging, Faezeh Vedaei, Najmeh Mashhadi, Mahdi Alizadeh, George Zabrecky, Daniel A. Monti, Md, Nancy Wintering, Emily Navarreto, Chloe Hriso, Andrew B. Newberg, Feroze B. Mohamed

Department of Radiology Faculty Papers

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and …

Early Management Of Adult Traumatic Spinal Cord Injury In Patients With Polytrauma: A Consensus And Clinical Recommendations Jointly Developed By The World Society Of Emergency Surgery (Wses) & The European Association Of Neurosurgical Societies (Eans), Edoardo Picetti, Andreas Demetriades, Fausto Catena, Bizhan Aarabi, Fikri Abu-Zidan, Oscar Alves, Luca Ansaloni, Rocco Armonda, Rafael Badenes, Miklosh Bala, Zsolt J Balogh, Andrea Barbanera, Alessandro Bertuccio, Walter Biffl, Pierre Bouzat, Andras Buki, Ana Maria Castano-Leon, Davide Cerasti, Giuseppe Citerio, Federico Coccolini, Raul Coimbra, Carlo Coniglio, Francesco Costa, Federico De Iure, Bart Depreitere, Enrico Fainardi, Michael Fehlings, Nikolay Gabrovsky, Daniel Agustin Godoy, Peter Gruen, Deepak Gupta, Gregory Hawryluk, Raimund Helbok, Iftakher Hossain, Peter Hutchinson, Corrado Iaccarino, Kenji Inaba, Marcel Ivanov, Stanislav Kaprovoy, Andrew Kirkpatrick, Sam Klein, Angelos Kolias, Nikolay Konovalov, Alfonso Lagares, Laura Lippa, Angelica Loza-Gomez, Teemu Luoto, Andrew Maas, Andrzej Maciejczak, Ronald Maier, Niklas Marklund, Matthew Martin, Ilaria Melloni, Sergio Mendoza-Lattes, Geert Meyfroidt, Marina Munari, Lena Napolitano, David Okonkwo, Yasuhiro Otomo, Marios Papadopoulos, Ondra Petr, Wilco Peul, Aichholz K Pudkrong, Zaffer Qasim, Frank Rasulo, Carla Reizinho, Florian Ringel, Sandro Rizoli, Elham Rostami, Andres Rubiano, Emanuele Russo, Aarti Sarwal, Jan Schwab, Franco Servadei, Deepak Sharma, Salman Sharif, Ehab Shiban, Lori Shutter, Philip Stahel, Fabio Taccone, Nicole Terpolilli, Claudius Thomé, Peter Toth, Parmenion Tsitsopoulos, Andrew Udy, Alex Vaccaro, Albert Varon, Monica Vavilala, Alexander Younsi, Monika Zackova, Tommaso Zoerle, Chiara Robba

Rothman Institute Papers

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.

METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.

RESULTS: A total of 17 statements were …

Treatment Effects Of N-Acetyl Cysteine On Resting-State Functional Mri And Cognitive Performance In Patients With Chronic Mild Traumatic Brain Injury: A Longitudinal Study, Faezeh Vedaei, Andrew B. Newberg, M. Alizadeh, George Zabrecky, Emily Navarreto, Chloe Hriso, Nancy Wintering, Feroze Mohamed, Daniel A. Monti

Marcus Institute of Integrative Health Faculty Papers

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups …

Standardized Pre-Clinical Surgical Animal Model Protocol To Investigate The Cellular And Molecular Mechanisms Of Ischemic Flap Healing, Edita Aksamitiene, Ryan Heffelfinger, Jan Hoek, Edmund Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. …

Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Associations Of Galectin-3 Levels With Measures Of Vascular Disease In Patients With Rheumatoid Arthritis, Amanda Nussdorf, Elizabeth Park, Isabelle Amigues, Laura Geraldino-Pardilla, Sabahat Bokhari, Jon T. Giles, Joan M. Bathon

Division of Rheumatology Faculty Papers

OBJECTIVES: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA).

METHODS: RA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic …

The Development Of A Rabies Virus-Vectored Vaccine Against Borrelia Burgdorferi, Targeting Bbi39, Shantel Rios, Bibek Bhattachan, Kruthi Vavilikolanu, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine …

Therapeutic Antibodies For The Prevention And Treatment Of Cancer, Mukesh Kumar, Akansha Jalota, Sushil Kumar Sahu, Shabirul Haque

Department of Medical Oncology Faculty Papers

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against …

Sepsis Epidemiology In Australian And New Zealand Children (Sentinel): Protocol For A Multicountry Prospective Observational Study, Elliot Long, Meredith L. Borland, Shane George, Shefali Jani, Eunicia Tan, Jocelyn Neutze, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Sonia Singh, Ben Gelbart, Sarah Mcnab, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Amanda Williams, Franz E. Babl

Department of Pediatrics Faculty Papers

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will …

Structural Basis For Nuclear Import Of Hepatitis B Virus (Hbv) Nucleocapsid Core, Ruoyu Yang, Ying-Hui Ko, Fenglin Li, Ravi K. Lokareddy, Chun-Feng David Hou, Christine Kim, Shelby Klein, Santiago Antolínez, Juan F. Marín, Carolina Pérez-Segura, Martin F. Jarrold, Adam Zlotnick, Jodi A. Hadden-Perilla, Gino Cingolani

Student Papers, Posters & Projects

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 …