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Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock Feb 2023

Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock

Wills Eye Hospital Papers

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.

Objectives: …


Parp1 Associates With R-Loops To Promote Their Resolution And Genome Stability, Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean-Yves Masson, Elise Fouquerel Feb 2023

Parp1 Associates With R-Loops To Promote Their Resolution And Genome Stability, Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean-Yves Masson, Elise Fouquerel

Student Papers, Posters & Projects

PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA-DNA hybrid and a displaced non-template DNA strand. R-loops are involved in crucial physiological processes but can also be a source of genome instability if persistently unresolved. In this study, we demonstrate that PARP1 binds R-loops in vitro and associates with R-loop formation …


Profibrotic Behavior Of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness, Benjamin A. Hendy, Jolanta Fertala, Thema Nicholson, Joseph A. Abboud, Surena Namdari, Andrzej Fertala Feb 2023

Profibrotic Behavior Of Fibroblasts Derived From Patients That Develop Posttraumatic Shoulder Stiffness, Benjamin A. Hendy, Jolanta Fertala, Thema Nicholson, Joseph A. Abboud, Surena Namdari, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND AND AIMS: Arthrofibrosis is a severe scarring condition characterized by joint stiffness and pain. Fundamental to developing arthrofibrotic scars is the accelerated production of procollagen I, a precursor of collagen I molecules that form fibrotic deposits in affected joints. The procollagen I production mechanism comprises numerous elements, including enzymes, protein chaperones, and growth factors. This study aimed to elucidate the differences in the production of vital elements of this mechanism in surgical patients who developed significant posttraumatic arthrofibrosis and those who did not.

METHODS: We studied a group of patients who underwent shoulder arthroscopic repair of the rotator cuff. …


Acute Systemic Infection-Associated Russell Body Gastroesophagitis: A Case Report And Literature Review, Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang Feb 2023

Acute Systemic Infection-Associated Russell Body Gastroesophagitis: A Case Report And Literature Review, Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang

Division of Gastroenterology and Hepatology Faculty Papers

Russell body esophagitis/gastritis (RBG) is a rare gastrointestinal inflammatory condition characterized by accumulation of plasma cells containing dense eosinophilic cytoplasmic inclusions, i.e., Russell bodies. Herein, we report a case of RBG in a patient with a systemic inflammation background. A 61-year-old female presented with oral infection. Upper gastrointestinal endoscopy revealed patchy salmon-colored esophageal mucosa proximally to the gastroesophageal junction, suggestive of “Barrett’s esophagus”. Histologic examination of the biopsy tissue from the lower esophagus showed diffuse lymphoplasmacytic infiltration with abundant admixed enlarged plasma cells (Mott cells) containing bright eosinophilic, round, dense, homogenous inclusions (Russell bodies) in cytoplasm. Immunohistochemical study demonstrated membranous …


Factors Associated With Response To Growth Hormone In Pediatric Growth Disorders: Results Of A 5-Year Registry Analysis, Judith L. Ross, Moshe Fridman, Nicky Kelepouris, Kristine Murray, Nils Krone, Michel Polak, Tilman R Rohrer, Alberto Pietropoli, Neil Lawrence, Philippe Backeljauw Feb 2023

Factors Associated With Response To Growth Hormone In Pediatric Growth Disorders: Results Of A 5-Year Registry Analysis, Judith L. Ross, Moshe Fridman, Nicky Kelepouris, Kristine Murray, Nils Krone, Michel Polak, Tilman R Rohrer, Alberto Pietropoli, Neil Lawrence, Philippe Backeljauw

Department of Pediatrics Faculty Papers

Context: Growth hormone (GH) therapy can increase linear growth in patients with growth hormone deficiency (GHD), Turner syndrome (TS), Noonan syndrome (NS), and Prader-Willi syndrome (PWS), although outcomes vary by disease state.

Objective: To assess growth and identify factors associated with growth response with long-term GH therapy.

Methods: Data from pediatric patients with GHD, TS, NS, and PWS obtained at GH treatment initiation (baseline) and annually for 5 years in the ANSWER Program and NordiNet® IOS were analyzed retrospectively. Height standard deviation score (HSDS) was assessed over time, and multivariate analyses determined variables with significant positive effects on growth outcomes …


Akt/Mtor Signaling Modulates Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Metastatic Breast Cancers, Maysa M. Abu-Khalaf, K. Alex Hodge, Christos Hatzis, Elisa Baldelli, Emna El Gazzah, Frances Valdes, William M. Sikov, Monica M. Mita, Neelima Denduluri, Rita Murphy, Daniel Zelterman, Lance Liotta Feb 2023

Akt/Mtor Signaling Modulates Resistance To Endocrine Therapy And Cdk4/6 Inhibition In Metastatic Breast Cancers, Maysa M. Abu-Khalaf, K. Alex Hodge, Christos Hatzis, Elisa Baldelli, Emna El Gazzah, Frances Valdes, William M. Sikov, Monica M. Mita, Neelima Denduluri, Rita Murphy, Daniel Zelterman, Lance Liotta

Kimmel Cancer Center Faculty Papers

Endocrine therapy (ET) in combination with CDK4/6 inhibition is routinely used as first-line treatment for HR+/HER2− metastatic breast cancer (MBC) patients. However, 30–40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven protein/phosphoprotein-based approach to identify predictive markers of response to ET plus CDK4/6 inhibition in pre-treatment tissue biopsies. Pathway-centered signaling profiles were generated from microdissected tumor epithelia and surrounding stroma/immune cells using the reverse phase protein microarray. Phosphorylation levels of the CDK4/6 downstream substrates Rb (S780) and FoxM1 (T600) were higher in patients with progressive disease (PD) compared to responders (p = …


Atezolizumab-Induced Psoriasiform Drug Eruption Successfully Treated With Ixekizumab: A Case Report And Literature Review, Laura Gleason, E Hunter, Alexa J. Cohen, Jayson Suriano, Neda Nikbakht Feb 2023

Atezolizumab-Induced Psoriasiform Drug Eruption Successfully Treated With Ixekizumab: A Case Report And Literature Review, Laura Gleason, E Hunter, Alexa J. Cohen, Jayson Suriano, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immune-related cutaneous adverse events (ircAE) are commonly seen with immune checkpoint inhibitors such as atezolizumab. Atezolizumab-induced psoriasis has been previously reported as an ircAE, especially in patients with pre-existing psoriasis. The severity of the reaction influences treatment of the cutaneous eruption. Biologics should be considered as a treatment option for severe refractory psoriasiform eruptions even in patients with complex medical conditions like chronic infections and malignancy. This is the first reported case of successful treatment of atezolizumab-induced psoriasiform eruption with ixekizumab, a neutralizing IL17A monoclonal antibody, to the best of our knowledge. Herein, we present a 63-year-old man with a …


60 Year Old Male With Autonomic Dysreflexia In C7 Ais A Secondary To A Suprapubic Catheter Inflation In The Membranous Urethra, Brandon Kase, Md, Joshua Levin, Do, Kristin Gustafson, Do Feb 2023

60 Year Old Male With Autonomic Dysreflexia In C7 Ais A Secondary To A Suprapubic Catheter Inflation In The Membranous Urethra, Brandon Kase, Md, Joshua Levin, Do, Kristin Gustafson, Do

Department of Rehabilitation Medicine Posters

Introduction: Autonomic dysreflexia is a potentially lifethreatening complication in patients with a spinal cord injury above the level of T6. A dangerous symptom is an increase in blood pressure induced by reflex sympathetic hyperactivity secondary to a noxious stimuli which can lead to cerebral hemorrhages, seizures, heart failure or pulmonary edema.1 The most common causes of autonomic dysreflexia are noxious stimuli to the 1) bladder such as urinary tract infection, distension, or catheterization; 2) bowel, such as constipation or 3) skin such as wounds, or tight clothing. Though Foley catheters and intermittent catheterizations are well known causes of dysreflexia …


Steroid Treatment Causes Weakness In Spinal Dural Arteriovenous Fistula, Mina Na, Do, Brandon Kase, Md, Roger Liu, Do, Kristin Gustafson, Do Feb 2023

Steroid Treatment Causes Weakness In Spinal Dural Arteriovenous Fistula, Mina Na, Do, Brandon Kase, Md, Roger Liu, Do, Kristin Gustafson, Do

Department of Rehabilitation Medicine Posters

Introduction: Spinal dural arteriovenous fistula (SDAVF) is an abnormal connection between the arterial and venous system creating an increase in blood flow and pressure into the spinal veins1 at an estimated frequency of 5-10 cases per million per year.2 Activities that increase intrathoracic and venous pressure such as Valsalva, abdominal compression and steroids2 can lead to a venous infarction, subarachnoid hemorrhage, paraplegia or tetraplegia.3 SDAVF is difficult to diagnose as it presents similarly to other neurologic disorders, but if diagnosed early, deficits can be prevented and reversed with intervention.1

Case Description: A 54-year-old male presented …


Novel Therapeutic Targets For Migraine, Areeba Nisar, Zubair Ahmed, Hsiangkuo Yuan Feb 2023

Novel Therapeutic Targets For Migraine, Areeba Nisar, Zubair Ahmed, Hsiangkuo Yuan

Department of Jefferson Headache Center Papers and Presentations

Migraine, a primary headache disorder involving a dysfunctional trigeminal vascular system, remains a major debilitating neurological condition impacting many patients’ quality of life. Despite the success of multiple new migraine therapies, not all patients achieve significant clinical benefits. The success of CGRP pathway-targeted therapy highlights the importance of translating the mechanistic understanding toward effective therapy. Ongoing research has identified multiple potential mechanisms in migraine signaling and nociception. In this narrative review, we discuss several potential emerging therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, δ-opioid receptor (DOR), potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels …


Real-World Maintenance Therapy And Survival Outcomes For Pembrolizumab Plus Pemetrexed And Platinum For Non-Small-Cell Lung Cancer In Usa, Himani Aggarwal, Kayonda Bayo, Yimei Han, Catherine Elizabeth Muehlenbein, Yajun Emily Zhu, Jong Seok Kim Feb 2023

Real-World Maintenance Therapy And Survival Outcomes For Pembrolizumab Plus Pemetrexed And Platinum For Non-Small-Cell Lung Cancer In Usa, Himani Aggarwal, Kayonda Bayo, Yimei Han, Catherine Elizabeth Muehlenbein, Yajun Emily Zhu, Jong Seok Kim

Student Papers, Posters & Projects

Aim: To evaluate treatment patterns and overall survival (OS) in real world metastatic non-squamous non-small-cell lung cancer (NSQ-NSCLC) patients that received pembrolizumab plus pemetrexed-platinum (pembro+pem+plat) aligned with KEYNOTE-189.

Materials & methods: OS was evaluated for the overall cohort and maintenance therapy (MT) subgroups and analyzed using Kaplan-Meier estimates and Cox proportional hazards model.

Results: Of 2488 patients that received first-line treatment, 45.1% received less than four cycles of pembro+pem+plat, 43.9% received four cycles plus MT with pembro and/or pem, and 11.1% received four cycles without continuing on MT. The median OS was 21.0 months and 9.1 months in patients that …


Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman Feb 2023

Intestinal Neuropod Cell Gucy2c Regulates Visceral Pain, Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting …


Rare Case Of Nasal Vault Oncocytic Cystadenoma, Aarti Agarwal, Kathleen Mcclain, Karen Banker, Kudakwashe Chikwava, Udayan K. Shah Feb 2023

Rare Case Of Nasal Vault Oncocytic Cystadenoma, Aarti Agarwal, Kathleen Mcclain, Karen Banker, Kudakwashe Chikwava, Udayan K. Shah

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Oncocytic Cystadenomas are a rare benign pathology often found to arise from the salivary glands, reported more commonly in minor salivary glands, but even more rarely in major salivary glands and the larynx. This is the first known report of a nasal vault oncocytic cystadenoma in a pediatric patient.

Methods: Case Report and Literature Review.

Case presentation: A 10-year-old female presented with a mass involving the left nasal vestibule that caused nasal obstruction and a visible external abnormality. MRI imaging revealed a cystic lesion in the anterior nasal cavity that was rim enhancing with a bright T2 signal that …


Estimated Impact Of Low Isolate Numbers On The Reliability Of Cumulative Antibiogram Data, Christian Tran, John Hargy, Bryan Hess, Matthew Pettengill Feb 2023

Estimated Impact Of Low Isolate Numbers On The Reliability Of Cumulative Antibiogram Data, Christian Tran, John Hargy, Bryan Hess, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Antibiograms are cumulative reports of antimicrobial susceptibility results that are used to guide the selection of empirical antibiotic therapy. Although Clinical and Laboratory Standards Institute (CLSI) guidelines recommend including only organisms that have at least 30 isolates in an antibiogram, previous studies demonstrated that adherence to this recommendation is highly variable. This paper aims to model the impact of small sample sizes on expected levels of error in cumulative antibiograms by comparing percent susceptibility results for random samples to those of the larger, entire data set. The results demonstrate relatively high error rates when utilizing low numbers of isolates in …


Mir-218-5p/Egfr Signaling In Arsenic-Induced Carcinogenesis, Ranakul Islam, Lei Zhao, Xiujuan Zhang, Ling-Zhi Liu Feb 2023

Mir-218-5p/Egfr Signaling In Arsenic-Induced Carcinogenesis, Ranakul Islam, Lei Zhao, Xiujuan Zhang, Ling-Zhi Liu

Department of Medical Oncology Faculty Papers

Background: Arsenic is a well-known carcinogen inducing lung, skin, bladder, and liver cancer. Abnormal epidermal growth factor receptor (EGFR) expression is common in lung cancer; it is involved in cancer initiation, development, metastasis, and treatment resistance. However, the underlying mechanism for arsenic-inducing EGFR upregulation remains unclear.

Methods: RT-PCR and immunoblotting assays were used to detect the levels of miR-218-5p and EGFR expression. The Luciferase assay was used to test the transcriptional activity of EGFR mediated by miR-218-5p. Cell proliferation, colony formation, wound healing, migration assays, tube formation assays, and tumor growth assays were used to study the function of miR-218-5p/EGFR …


Errorless, Errorful, And Retrieval Practice For Naming Treatment In Aphasia: A Scoping Review Of Learning Mechanisms And Treatment Ingredients, Kristen Nunn, Sofia Vallila-Rohter, Erica L. Middleton Feb 2023

Errorless, Errorful, And Retrieval Practice For Naming Treatment In Aphasia: A Scoping Review Of Learning Mechanisms And Treatment Ingredients, Kristen Nunn, Sofia Vallila-Rohter, Erica L. Middleton

Moss-Magee Rehabilitation Papers

PURPOSE: Increasingly, mechanisms of learning are being considered during aphasia rehabilitation. Well-characterized learning mechanisms can inform "how" interventions should be administered to maximize the acquisition and retention of treatment gains. This systematic scoping review mapped hypothesized mechanisms of action (MoAs) and treatment ingredients in three learning-based approaches targeting naming in aphasia: errorless learning (ELess), errorful learning (EFul), and retrieval practice (RP). The rehabilitation treatment specification system was leveraged to describe available literature and identify knowledge gaps within a unified framework.

METHOD: PubMed and CINHAL were searched for studies that compared ELess, EFul, and/or RP for naming in aphasia. Independent reviewers …


Harnessing Transcriptionally Driven Chromosomal Instability Adaptation To Target Therapy-Refractory Lethal Prostate Cancer., Brittiny Dhital, Sandra Santasusagna, Perumalraja Kirthika, Michael Xu, Peiyao Li, Marc Carceles-Cordon, Rajesh K. Soni, Zhuoning Li, Ronald C. Hendrickson, Matthew J. Schiewer, William K. Kelly, Cora N. Sternberg, Jun Luo, Amaia Lujambio, Carlos Cordon-Cardo, Monica Alvarez-Fernandez, Marcos Malumbres, Haojie Huang, Adam Ertel, Josep Domingo-Domenech, Veronica Rodriguez-Bravo Feb 2023

Harnessing Transcriptionally Driven Chromosomal Instability Adaptation To Target Therapy-Refractory Lethal Prostate Cancer., Brittiny Dhital, Sandra Santasusagna, Perumalraja Kirthika, Michael Xu, Peiyao Li, Marc Carceles-Cordon, Rajesh K. Soni, Zhuoning Li, Ronald C. Hendrickson, Matthew J. Schiewer, William K. Kelly, Cora N. Sternberg, Jun Luo, Amaia Lujambio, Carlos Cordon-Cardo, Monica Alvarez-Fernandez, Marcos Malumbres, Haojie Huang, Adam Ertel, Josep Domingo-Domenech, Veronica Rodriguez-Bravo

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as a therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis of patient datasets, we find that castration and chemotherapy-resistant tumors display the highest CIN and mitotic kinase levels. Functional genomics screening coupled with quantitative phosphoproteomics identify MASTL kinase as a survival vulnerability specific of chemotherapy-resistant PCa cells. Mechanistically, MASTL upregulation is driven by transcriptional rewiring mechanisms involving the non-canonical transcription factors androgen receptor splice variant 7 and E2F7 in a circuitry that restrains deleterious CIN and …


Severe Ocular Alkali Injury Managed With An Externally Sutured Amniotic Membrane And Customized Symblepharon Ring, Sophia S. Lam, Bonnie Sklar, Marisa Schoen, Christopher J. Rapuano Feb 2023

Severe Ocular Alkali Injury Managed With An Externally Sutured Amniotic Membrane And Customized Symblepharon Ring, Sophia S. Lam, Bonnie Sklar, Marisa Schoen, Christopher J. Rapuano

Student Papers, Posters & Projects

Alkali injuries are ocular emergencies that require immediate evaluation and therapy to preserve vision. Severe alkali injuries can result in long‑term vision‑threatening sequelae including symblepharon, corneal ulceration, corneal scarring, limbal stem cell deficiency, xerophthalmia, cicatricial changes of the eyelid and adnexa, glaucoma, uveitis, and permanent vision loss. Treatment is aimed at neutralizing the pH, controlling inflammation, and restoring the ocular surface. Here, we present the case of a 35‑year‑old male who sustained direct ocular exposure to sodium hydroxide, resulting in significant corneal and conjunctival epithelial defects despite aggressive initial medical therapy. The patient subsequently received a large, externally sutured amniotic …


A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update., Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor Feb 2023

A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update., Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor

Department of Medicine Faculty Papers

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff …


Variance In Management Of Extracorporeal Membrane Oxygenation-Associated Fibrin Sheaths At A Single Institution, Alexandra Tedesco Md, Monica Majumdar Md, Jamel P. Ortoleva Md, Christine Nayar Md, Masashi Kawabori Md, Payam Salehi Md, Ali Irshad Md Feb 2023

Variance In Management Of Extracorporeal Membrane Oxygenation-Associated Fibrin Sheaths At A Single Institution, Alexandra Tedesco Md, Monica Majumdar Md, Jamel P. Ortoleva Md, Christine Nayar Md, Masashi Kawabori Md, Payam Salehi Md, Ali Irshad Md

Abington Jefferson Health Papers

Objective: Extracorporeal membrane oxygenation (ECMO) support for patients with cardiac or respiratory failure has been increasingly used by advanced critical care practitioners. The thromboembolic complications of ECMO have been extensively discussed and researched; however, research and discussion on the development, risks, and management of cannulae-associated fibrin sheaths are lacking.

Methods: Institutional review board approval was not required. We have presented three cases detailing the identifi- cation and individualized management of ECMO-associated fibrin sheaths at our institution. The three patients provided written informed consent for the report of their case details and imaging studies.

Results: Of our three patients with ECMO-associated …


Retrospective Analyses Of The Outcomes Among Hospitalized Liver Cirrhosis Patients With Heart Failure And Covid-19 Infection: Insight From The National Inpatient Sample, Bruce Adrian Casipit, Hussein Al-Sudani, Ahmer Khan, Emmanuel Akuna, Aman Amanullah Feb 2023

Retrospective Analyses Of The Outcomes Among Hospitalized Liver Cirrhosis Patients With Heart Failure And Covid-19 Infection: Insight From The National Inpatient Sample, Bruce Adrian Casipit, Hussein Al-Sudani, Ahmer Khan, Emmanuel Akuna, Aman Amanullah

Division of Cardiology Faculty Papers

Background: There is paucity of data regarding the impact of Coronavirus Disease 2019 (COVID-19) infection on the outcomes of hospitalized liver cirrhosis (LC) patients with heart failure (HF).

Methods: Utilizing the 2020 National Inpatient Sample (NIS) Database, we conducted a retrospective cohort study to investigate the outcomes of hospitalized LC patients with HF and COVID-19 infection, looking at its impact on in-hospital mortality, risk for acute kidney injury (AKI) and length of stay (LOS).

Results: We identified a total of 10,810 hospitalized LC patients with HF, of which 1.39 % (n = 150/10,810) had COVID-19 infection. Using a stepwise survey …


Opioid Prescriptions In A Veteran Population Undergoing Lumbar Spine Surgery: What Are The Current Knowledge Gaps?, Mark J. Lambrechts, Hernan Roca, Brian A. Karamian Feb 2023

Opioid Prescriptions In A Veteran Population Undergoing Lumbar Spine Surgery: What Are The Current Knowledge Gaps?, Mark J. Lambrechts, Hernan Roca, Brian A. Karamian

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.


Sphenopalatine Artery Pseudoaneurysm Formation Following Facial Trauma: A Case Report And Literature Review, Kareem El Naamani, Stephen Capone, Ching-Jen Chen, Lisa Tartaglino, Marc Rosen, Rawad Abbas, Georgios S. Sioutas, Abdelaziz Amllay, Adam Hunt, Michael Reid Gooch, Nabeel Herial, Pascal Jabbour, Robert H. Rosenwasswer, Stavropoula Tjoumakaris Feb 2023

Sphenopalatine Artery Pseudoaneurysm Formation Following Facial Trauma: A Case Report And Literature Review, Kareem El Naamani, Stephen Capone, Ching-Jen Chen, Lisa Tartaglino, Marc Rosen, Rawad Abbas, Georgios S. Sioutas, Abdelaziz Amllay, Adam Hunt, Michael Reid Gooch, Nabeel Herial, Pascal Jabbour, Robert H. Rosenwasswer, Stavropoula Tjoumakaris

Department of Neurosurgery Faculty Papers

Facial fractures, specifically orbitozygomatic and zygomaticomaxillary complex fractures, are well-documented and common injuries. Pseudoaneurysm formation following cerebrovascular blunt trauma is a rarely experienced complication with an incidence rate of less than 1% with only a few cases reported in the literature. Traumatic pseudoaneurysm formation of the sphenopalatine artery (SPA), the deepest branch of the maxillary artery, is extremely rare due to the deep location of the SPA and its protection from bony landmarks. In craniofacial trauma, pseudoaneurysm formation is not apparent on physical examination due to its deep location and usually presents as persistent nasal bleeding. SPA pseudoaneurysms can present …


Current And Emerging Therapies For Atherosclerotic Cardiovascular Disease Risk Reduction In Hypertriglyceridemia, Reed Mszar, Sarah Bart, Alexander Sakers, Daniel Soffer, Dean G. Karalis Feb 2023

Current And Emerging Therapies For Atherosclerotic Cardiovascular Disease Risk Reduction In Hypertriglyceridemia, Reed Mszar, Sarah Bart, Alexander Sakers, Daniel Soffer, Dean G. Karalis

Division of Cardiology Faculty Papers

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis …


An Updated Classification Of Meditation Methods Using Principles Of Taxonomy And Systematics, Jonathan D. Nash, Andrew B. Newberg Feb 2023

An Updated Classification Of Meditation Methods Using Principles Of Taxonomy And Systematics, Jonathan D. Nash, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

This paper revisits the proposal for the classification of meditation methods which we introduced in our initial 2013 publication, “Toward a Universal Taxonomy and Definition of Meditation”. At that time, we advanced the thesis that meditation methods could be effectively segregated into three orthogonal categories by integrating the taxonomic principle of functional essentialism and the paradigm of Affect and Cognition; and we presented relevant research findings which supported that assertion. This iteration expands upon those theoretical and methodological elements by articulating a more comprehensive Three Tier Classification System which accounts for the full range of meditation methods; and demonstrates how …


Effects Of Adjuvants In A Rabies-Vectored Ebola Virus Vaccine On Protection From Surrogate Challenge, Catherine Yankowski, Drishya Kurup, Christoph Wirblich, Matthias J. Schnell Feb 2023

Effects Of Adjuvants In A Rabies-Vectored Ebola Virus Vaccine On Protection From Surrogate Challenge, Catherine Yankowski, Drishya Kurup, Christoph Wirblich, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50-90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping …


New Psychoactive Substances Intoxications And Fatalities During The Covid-19 Epidemic, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Tommaso Cassano, Gregory Dendramis, Eva Montanari, Marche Polytechnic University, Paolo Beretta, Simona Zaami, Francesco Paolo Busardò, Marilyn Ann Huestis Feb 2023

New Psychoactive Substances Intoxications And Fatalities During The Covid-19 Epidemic, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Tommaso Cassano, Gregory Dendramis, Eva Montanari, Marche Polytechnic University, Paolo Beretta, Simona Zaami, Francesco Paolo Busardò, Marilyn Ann Huestis

Institute of Emerging Health Professions Faculty Papers

In January 2020, the World Health Organization (WHO) issued a Public Health Emergency of International Concern, declaring the COVID-19 outbreak a pandemic in March 2020. Stringent measures decreased consumption of some drugs, moving the illicit market to alternative substances, such as New Psychoactive Substances (NPS). A systematic literature search was performed, using scientific databases such as PubMed, Scopus, Web of Science and institutional and government websites, to identify reported intoxications and fatalities from NPS during the COVID-19 pandemic. The search terms were: COVID-19, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, intox*, fatal*, new psychoactive substance, novel psychoactive …


Modeling And Analysis Of The Intrinsic Cardiac Nervous System In Closed-Loop Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli Feb 2023

Modeling And Analysis Of The Intrinsic Cardiac Nervous System In Closed-Loop Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The baroreceptor reflex is a multi-input, multi-output physiological control system that regulates short-term blood pressure by modulating nerve activity between the brainstem and the heart. The computational model by Park et al. (2020) is the most recent iteration in our exploration of the system. However, the contributions of”the little brain of the heart”, the intrinsic cardiac nervous system (ICN), to local control of the heart and to the integration of sensory information is unknown and has been overlooked in previous models. We have incorporated a high-fidelity representation of the ICN into a model of the baroreceptor reflex based on anatomical, …


Evaluation Of Autofluorescence Technology In The Identification Of Tissue Types In Anterior Neck Surgery, Natalie M. Perlov, Elliott Sina, Sruti Tekumalla, Annie Moroco, Md, Elizabeth Cottrill, Md Feb 2023

Evaluation Of Autofluorescence Technology In The Identification Of Tissue Types In Anterior Neck Surgery, Natalie M. Perlov, Elliott Sina, Sruti Tekumalla, Annie Moroco, Md, Elizabeth Cottrill, Md

Alpha Omega Alpha Research Symposium Posters

Background

  • Iatrogenic parathyroidectomy and hypocalcemia are potential risks of central neck surgery1
  • Resected parathyroid tissue may be reimplanted if identified quickly, mitigating risk of hypocalcemia2
  • Current practices of identifying and preserving parathyroids, such as frozen specimens, may incur significant costs in time and expense
  • Autofluorescence (AF) technology takes baseline AF readings from healthy thyroid tissue and compares to other tissues in the neck
  • There is limited data on AF profiles of all tissue types in the central neck (thyroid, thymus, benign vs. malignant lymph nodes, adipose tissue)

Preliminary Outcomes

  • (1) Investigate the impact of AF on iatrogenic hypoparathyroidism …


Broad Efficacy Of A Computationally Designed Ace2 Decoy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme W. Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam Feb 2023

Broad Efficacy Of A Computationally Designed Ace2 Decoy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme W. Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam

Alpha Omega Alpha Research Symposium Posters

Background: The SARS-CoV-2 omicron variant (B.1.1.529) and its sublineages are currently the dominant variants in the United States accounting for 100% of COVID-19 cases. Problem: The S protein receptor-binding domain (RBD), located in the S1 subunit of the S protein, binds the human angiotensin-converting enzyme 2 (hACE2) leading to S1 shedding and proteolytic processing of S2 that is important for membrane fusion and release of viral RNA. Various neutralizing therapeutics including protein minibinders, peptides, monoclonal antibodies, and nanobodies have been developed to block the critical interaction between the RBD and hACE2. However, these therapeutics are often developed against the S …