Therapeutics Commons^™

Hepatic Manifestations Following Gene Therapy, Akash Roy, Shalini Bansal, Anand Kulkarni, K. Rajender Reddy

SKMC Student Presentations and Publications

Gene therapy involves the introduction of genetic materials, most commonly using viral vectors, to alter gene expression to ameliorate or cure disease symptoms with minimal adverse events. While interest in gene therapy has been on the increase, concerns have arisen about the potential for hepatotoxicity, which arises from diverse mechanisms. While viral vectors can produce dose-dependent hepatotoxicity secondary to integration, immune responses appear to be the primary driving mechanism. A mild increase in aminotransferases is the most common hepatic manifestation, occurring variably in 20%-80%, while there has been rare progress to acute liver failure. The occurrence of hepatotoxicity is unpredictable …

Adjuvant Radiotherapy In Pt3-4n0m0 Major Salivary Gland Cancer Without Other Adverse Features, Aman M. Patel, Afash Haleem, Praneet C. Kaki, Jake J. Lee, Russell Maxwell, Jason A. Brant, Robert M. Brody, Ryan M. Carey

SKMC Student Presentations and Publications

OBJECTIVE: To investigate adjuvant radiotherapy (aRT) utilization and associated differences in overall survival (OS) in pT3-4N0M0 major salivary gland cancer (MSGC) without evidence of other adverse pathologic features.

METHODS: The 2006 to 2018 National Cancer Database was queried for patients with MSGC classified as pT3-4N0M0. Patients with evidence of lymphovascular invasion or positive surgical margins were excluded. Multivariable binary logistic and Cox regression models adjusting for patient demographics, pathologic features including histology, and treatment were implemented.

RESULTS: Of 897 patients satisfying inclusion criteria, 368 (41.0 %) underwent aRT. Compared with those not undergoing aRT, patients undergoing aRT were younger (median …

Optimizing Transcutaneous Spinal Cord Stimulation: An Exploratory Study On The Role Of Electrode Montages And Stimulation Intensity On Reflex Pathway Modulation, Shirin Madarshahian, Michael Trakhtorchuck, Tatiana Guerrero, Kristin Gustafson, James Harrop, Caio Matias, M. J. Mulcahey, Alessandro Naopli, Alex Vaccaro, Mijail Serruya

Farber Institute for Neuroscience Faculty Papers

Transcutaneous spinal cord stimulation (tSCS) is a promising non-invasive method to improve motor function in individuals with spinal cord injury (SCI) by enhancing spinal reflex pathways. This study aimed to investigate the effects of different tSCS electrode placement montages and targeted spinal levels on neurophysiological responses such as spinally evoked motor responses (sEMRs), dorsal root reflex activation, and muscle recruitment in individuals with SCI and healthy controls to optimize stimulation strategies for motor recovery. Five participants (three individuals with SCI and two controls) underwent transcutaneous spinal cord stimulation using various electrode montages, target spinal level stimulation, and single- and paired-pulse …

3d-Printed Organ-Realistic Phantoms To Verify Quantitative Spect/Ct Accuracy For 177lu-Psma-617 Treatment Planning, Lydia J. Wilson, Sara Belko, Eric L. Gingold, Shuying Wan, Rachel Monane, Robert S. Pugliese, Firas Mourtada

Department of Radiation Oncology Faculty Papers

Background/Objectives: Accurate patient-specific dosimetry is essential for optimizing radiopharmaceutical therapy (RPT), but current tools lack validation in clinically realistic conditions. This work aimed to develop a workflow for designing and fabricating patient-derived, organ-realistic RPT phantoms and evaluate their feasibility for commissioning patient-specific RPT radioactivity quantification. Methods: We used computed tomographic (CT) and magnetic resonance (MR) imaging of representative patients, computer-aided design, and in-house 3D printing technology to design and fabricate anthropomorphic kidney and parotid phantoms with realistic organ spacing, anatomically correct orientation, and surrounding tissue heterogeneities. We evaluated the fabrication process via geometric verification (i.e., volume comparisons) and leak testing …

Quantifying Patient Preferences For Treatments For Refractory Chronic Spontaneous Urticaria, Olufemi Babalola, Richard W. Hass, John F Mcana, Manav Segal, Juan Marcos Gonzalez, Olajumoke Fadugba

College of Population Health Faculty Papers

BACKGROUND: In recent years, it has become increasingly common to incorporate the patient perspective into drug development and regulatory decision making.

OBJECTIVE: This study aimed to measure and quantify patient preferences (priorities and trade-offs) for attributes that characterize current and emerging refractory chronic spontaneous urticaria (rCSU) treatments.

METHODS: Adult patients with self-reported rCSU symptoms completed an online discrete choice experiment survey. The survey included 10 questions that asked respondents to choose between 2 hypothetical rCSU treatment profiles having similar attributes with varying levels. The attributes included the following: chance of control of symptoms, time to symptom control, return of symptoms …

Real-World Impact Of Latanoprostene Bunod Ophthalmic Solution 0.024% In Glaucoma Therapy: A Narrative Review, W. Daniel Stamer, Thomas Chiu, Da-Wen Lu, Tsing Hong Wang, Prin Rojanapongpun, Ngamkae Ruangvaravate, Youn Hye Jo, Marlene R. Moster, Murray Fingeret, Nora Lee Cothran, Jessica Steen, Ian B. Gaddie, Ömür Uçakhan-Gündüz, Wesam S. Shalaby, Cindy M. L. Hutnik

Wills Eye Hospital Papers

Latanoprostene bunod ophthalmic solution (LBN) 0.024% is a topical nitric oxide (NO)-donating prostaglandin F2α (PGF2α) analog first approved in November 2017 for reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG). This narrative review describes the unique mechanism of action of LBN and summarizes available real-world data. Upon instillation, LBN is metabolized into latanoprost acid and butanediol mononitrate, which is further reduced to NO and an inactive metabolite. Latanoprost acid increases aqueous humor outflow primarily through the uveoscleral (unconventional) pathway, whereas NO increases outflow through the trabecular (conventional) pathway. Eight studies were identified: 2 …

Effectiveness Of Intrapartum Azithromycin To Prevent Infections In Planned Vaginal Births In Low-Income And Middle-Income Countries: A Post-Hoc Analysis Of Data From A Multicentre, Randomised, Double-Blind Placebo-Controlled Trial, Waldemar A. Carlo, Alan T.N. Tita, Janet L. Moore, Musaku Mwenechanya, Elwyn Chomba, Jennifer J. Hemingway-Foday, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Adrien Lokangaka, Antoinette Tshefu, Melissa Bauserman, Jackie K. Patterson, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osayame Austine Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam Sunder Tikmani, Sarah Saleem, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William Petri, Manolo Mazariegos, Nancy F. Krebs, Denise C. Babineau, Elizabeth M. Mcclure, Marion Koso-Thomas, A-Plus Trial Group

Global Health Articles

Background

In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection.

Methods

We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The …

Impact Of Body Mass Index On Stroke In Extracorporeal Cardiopulmonary Resuscitation: Data From The Extracorporeal Life Support Organization Registry, Jin Kook Kang, Shi Nan Feng, Winnie Liu, Jiah Kim, Andrew Kalra, Patricia Brown, Christopher Wilcox, Daniel Brodie, Steven Keller, Bo Soo Kim, Glenn Whitman, Sung-Min Cho

SKMC Student Presentations and Publications

Objective: We aimed to characterize the impact of body mass index (BMI) on stroke in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). Methods: We queried the Extracorporeal Life Support Organization registry for patients receiving ECPR (2020-2024). Patients were categorized into five BMI groups: underweight (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), class 1 obesity (30-34.9 kg/m²), and class 2 obesity or above (≥35 kg/m²). A generalized additive model (GAM) analysis was used to identify the BMI range with the greatest stroke risk. Multivariable regression was used to compare odds of …

Stingers—A Review Of Current Understanding And Management, Teleale Gebeyehu, James Harrop, Stavros Matsoukas, Alexander Vaccaro

Department of Neurosurgery Faculty Papers

Abstract: A stinger is the transient sensory and motor loss of one upper extremity caused by a stretch or compression injury to the brachial plexus or the exiting cervical nerve roots. Athletes from contact sports like American football, rugby, wrestling, and horseback riding are most affected. Given today’s competitive athletic culture and recent advancements in sports medicine, understanding the clinical, diagnostic, and therapeutic aspects of stingers is crucial. Thus, this narrative review highlights current knowledge of pathology, clinical features, diagnostic modalities, radiologic measurements, management, rehabilitation, and return-to-play protocols. Recent and prominent English publications on adult athletes revealed that the brachial …

Comparing Postoperative Opioid Use In Primary And Revision Lumbar Fusion: A Propensity-Matched Analysis, Jonathan Dalton, Jarod Olson, Nicholas B. Pohl, Rajkishen Narayanan, Omar Tarawneh, Yunsoo Lee, Michael V. Carter, Gokul Karthikeyan, Logan Witt, Aayush Mehta, John J. Mangan, Mark F. Kurd, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: This study compared postoperative opioid use for patients undergoing short segment primary versus revision lumbar fusion.

METHODS: Patients who underwent primary or revision 1-2 level lumbar fusion (2017-2021) were included in this study. The state Prescription Drug Monitoring Program was reviewed for all patients to quantify preoperative and postoperative opioid, benzodiazepine, muscle relaxant, and gabapentin use. A 1:1 propensity match was performed to match primary lumbar fusion patients with revision lumbar fusion patients. Revision lumbar fusion patients were substratified into those with or without persistent postoperative opioid use to identify demographic differences between these patient cohorts.

RESULTS: The final …

Respiratory Muscle Training Reduces Painful Swallowing And Opioid Use During Radiation Therapy For Head And Neck Cancer: A Matched Pair Analysis, Andrew D. Ray, Chi-Chen Hong, Nicolas F. Schlecht, Han Yu, Kristopher Attwood, Kent L. Nastiuk, Bryan A. Spinelli, Ann Marie Flores, Hillary Jacobson, Julia Fulfaro, M. Jeffrey Mador, Austin J. Iovoli, Mark K. Farrugia, Anurag K. Singh

Department of Physical Therapy Faculty Papers

BACKGROUND: Patients with head and neck cancer (HNC) receiving radiation therapy (RT) are at increased risk for symptoms of oral mucositis (OM), opioid use, and declines in physical function, outcomes that contribute to increased morbidity and mortality. The study objective was to determine the effects of respiratory muscle training (RMT) on OM and opioid use, as well as functional performance in patients with HNC receiving RT with or without concurrent chemotherapy (CCRT).

METHODS: Patients aged ≥ 18 years of age with stage I to IV HNC being treated with RT or CCRT receiving a home-based respiratory muscle training (RMT) (n …

Chemoradiation Treatment With Or Without Concurrent Tumor-Treating Fields (Ttfields) Therapy In Newly Diagnosed Glioblastoma (Gbm) Patients In China, Liping Liang, Lingchao Chen, Chunxia Ni, Wenyin Shi, Zhirui Zhou, Shu Chen, Wenjia Zhu, Jiabing Liu, Xianxin Qiu, Wanzun Lin, Junyan Zhang, Zhiyong Qin, Yang Wang

Department of Radiation Oncology Faculty Papers

BACKGROUND: Tumor-treating fields (TTFields) therapy and radiotherapy may have synergistic anti-glioma effect based on preclinical studies. The combination of chemoradiation therapy (CRT) with TTFields therapy has noticeably attracted clinicians' attention. This study aimed to provide insights into the clinical outcomes of patients with newly diagnosed glioblastoma who received either concurrent CRT and TTFields therapy or adjuvant TTFields therapy following CRT. The findings were based on a cohort of patients who were treated at Huashan Hospital (Shanghai, China).

METHODS: This retrospective study analyzed ndGBM patients' clinical outcomes who were treated at Huashan Hospital and received TTFields therapy. Patients were categorized into …

A Randomized Phase Ii/Iii Study Of Paclitaxel/Carboplatin/Metformin Versus Paclitaxel/Carboplatin/Placebo As Initial Therapy For Measurable Stage Iii Or Iva, Stage Ivb, Or Recurrent Endometrial Cancer: An Nrg Oncology/Gog Study, Victoria L. Bae-Jump, Michael W. Sill, Paola A. Gehrig, Jason D. Merker, David L. Corcoran, Adam D. Pfefferle, Michele C. Hayward, Joan L. Walker, Andrea R. Hagemann, Steven E. Waggoner, Roisin E. O'Cearbhaill, Megan E. Mcdonald, Mitchell I. Edelson, Paul A. Disilvestro, Amy L. Mcnally, Aimee Fleury, Ramey D. Littell, Frederick R. Ueland, Heather A. Lankes, Carol Aghajanian

Abington Jefferson Health Papers

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

METHODS: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary …

Changes In Brain Functional Connectivity Associated With Transcutaneous Auricular Vagus Nerve Stimulation In Healthy Controls, Daniel A. Monti, Nancy Wintering, Faezeh Vedaei, Alicia Steinmetz, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

PURPOSE: A growing number of research studies have explored the potential effects of vagus nerve stimulation (VNS) on brain physiology as well as clinical effects particularly related to stress and anxiety. However, there currently are limited studies showing functional changes during different frequencies of stimulation and laterality effects transcutaneous auricular VNS (TaVNS). In this study, we evaluated whether TaVNS alters functional connectivity in the brain of healthy controls. We hypothesized that TaVNS would significantly alter connectivity in areas involved with emotional processing and regulation including the limbic areas, insula, frontal lobe regions, and cerebellum.

METHODS: We enrolled 50 healthy controls. …

The Advancement And Utility Of Multimodal Imaging In The Diagnosis Of Degenerative Disc Disease, Eric M. Teichner, Robert C. Subtirelu, Connor R. Crutchfield, Chitra Parikh, Arjun Ashok, Sahithi Talasila, Victoria Anderson, Milan Patel, Sricharvi Mannam, Andrew Lee, Thomas Werner, William Y. Raynor, Abass Alavi, Mona-Elisabeth Revheim

SKMC Student Presentations and Publications

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using ¹⁸F- fluorodeoxyglucose (FDG) and ¹⁸F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT grading of the disease. The novel hybrid imaging modality PET/MRI provides new opportunities and are briefly discussed. The complex pathophysiology of …

First Documented Case Of A Third-Generation Lvad Rotor Dislodgement, Tyler Lee, Chaitra Janga, Enad Haddad, Kevin Hagan, Donald C. Haas

Abington Jefferson Health Papers

The third-generation left ventricular assist device (3G-LVAD) has significantly reduced adverse events and hospitalizations compared with previous generations. This case presents a rare 3G-LVAD rotor dislodgement malfunction, not previously documented, in a 77-year-old man. Further research behind the malfunction is warranted for early prevention and appropriate management.

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

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 …

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 …

Incidence And Predictors Of Woven Endobridge (Web) Shape Modification Following Treatment Of Intracranial Aneurysms In A Large Multicenter Study, Nimer Adeeb, Hamza Adel Salim, Basel Musmar, Assala Aslan, Christian Swaid, Miguel Cuellar, Mahmoud Dibas, Nicole Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Amir Essibayi, Sunil Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Eytan Raz, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad Levy, Neil Haranhalli, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula Tjoumakaris, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vivek Yedavalli, Max Wintermark, Vitor Mendes Pereira, Aman Patel, Hugo Cuellar-Saenz, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is FDA-approved for the treatment of bifurcation aneurysms. Despite its wide popularity, it has been under scrutiny for its association with potential aneurysm recanalization and retreatment due to device shape modification. This study aims to analyze the shape modification rate of WEB devices and identify factors associated with this phenomenon, as well as its correlation with aneurysm retreatment. We conducted a retrospective review of the WorldWide WEB Consortium database, including adult patients treated for intracranial aneurysms with the WEB device. We assessed aneurysm occlusion using the WEB Occlusion Scale and defined WEB shape modification as …

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 …

Multi-Societal Expert Consensus Statement On The Safe Administration Of Ultrasound Contrast Agents, Jordan B. Strom, Andrew Appis, Richard G. Barr, Maria Cristina Chammas, Dirk-André Clevert, Kassa Darge, Linda Feinstein, Steven B. Feinstein, J. Brian Fowlkes, Beverly Gorman, Pintong Huang, Yuko Kono, Juan Lopez-Mattei, Andrej Lyshchik, Michael L. Main, Wilson Matthias, Christina Merrill, Sharon L. Mulvagh, Petros Nihoyannopoulos, Joan Olson, Fabio Piscaglia, Thomas Porter, Arnaldo Rabischoffsky, Roxy Senior, Jessica L Stout, Maria Stanczak, Stephanie R. Wilson

Department of Radiology Faculty Papers

Contrast enhanced ultrasound (CEUS) offers a safe, reliable imaging option to establish a clinical diagnosis across a variety of multidisciplinary settings. This Expert Consensus Statement serves to outline expert opinion on what constitutes appropriate supervision and the essential components of safe CEUS practice. The purpose of this document is to empower institutions to allow sonographers, along with other trained medical professionals, to administer UCAs at the point of care, consistent with the updated scope of practice documentation and within the broad parameters of an individual's training and licensure, while subject to appropriate supervision and meeting or exceeding minimum safety standards. …

Applications Of Machine Learning-Driven Molecular Models For Advancing Ophthalmic Precision Medicine, Rahul Kumar, Joshua Ong, Ethan Waisberg, Ryung Lee, Tuan Nguyen, Phani Paladugu, Maria C. Rivolta, Chirag Gowda, John V. Janin, Jeremy Saintyl, Dylan Amiri, Ansh Gosain, Ram Jagadeesan

SKMC Student Presentations and Publications

Ophthalmic diseases such as glaucoma, age-related macular degeneration (ARMD), and optic neuritis involve complex molecular and cellular disruptions that challenge current diagnostic and therapeutic approaches. Advanced artificial intelligence (AI) and machine learning (ML) models offer a novel lens to analyze these diseases by integrating diverse datasets, identifying patterns, and enabling precision medicine strategies. Over the past decade, applications of AI in ophthalmology have expanded from imaging-based diagnostics to molecular-level modeling, bridging critical gaps in understanding disease mechanisms. This paper systematically reviews the application of AI-driven methods, including reinforcement learning (RL), graph neural networks (GNNs), Bayesian inference, and generative adversarial networks …

The Road Ahead: Emerging Therapies For Primary Iga Nephropathy, Edward J. Filippone, Rakesh Gulati, John Farber

Division of Nephrology Faculty Papers

Primary IgA nephropathy (IgAN) is the most common form of primary glomerulopathy. A slowly progressive disease presenting in the young to middle-aged, most patients with reduced eGFR or proteinuria will progress to end-stage kidney disease (ESKD) in their lifetimes. The pathogenesis involves increased production of galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes that deposit in the glomerulus, eliciting mesangial cell proliferation, inflammation, and complement activation. The backbone of therapy is supportive, including lifestyle modifications, strict blood pressure control, and renin-angiotensin system inhibition targeting proteinuria < 300 mg/day. Sodium-glucose transporter 2 inhibitors are indicated for persisting proteinuria or declining eGFR. Sparsentan is indicated for persisting proteinuria. Immunosuppression should be considered for all patients at risk for progression (persisting proteinuria and/or declining eGFR). To reduce Gd-IgA1 production, targeted-release budesonide is approved. Agents targeting B cell survival factors APRIL or BAFF/APRIL have significantly reduced Gd-IgA1 production and proteinuria in phase 2 trials but await phase 3 data for approval. To reduce inflammation, high-dose steroids are ineffective and toxic in Caucasian patients, although lower-dose regimens may be effective in Chinese patients. Complement inhibition is being actively studied. The factor B inhibitor iptacopan has conditional approval. The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway.

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 …

Multimorbidity And Peak Oxygen Uptake In Patients Undergoing Cardiac Rehabilitation, Pauline F. Gomes, Audry Chacin-Suarez, Sophie A. Miller, Karen M. Fischer, Thomas P. Olson

Einstein Health Papers

No abstract provided.

Validation Of A Novel Landmark-Guided Intra-Articular Postero-Medial Surgeon-Administered Injection Technique, Nicolas Piuzzi, Andrew Spitzer, Jason Mussell, Ignacio Pasqualini, Stan Dysart, Jeffrey Gonzales, Michael Mont, Jess H. Lonner, Md, William Mihalko

Rothman Institute Papers

BACKGROUND: This study aimed to define an intra-articular surgeon-administered technique that may be comparable to ultrasound (US)-guided adductor canal block (ACB).

METHODS: Five cadaver lower limbs were examined. An anesthesiologist administered a US-guided ACB using 20 mL of dilute indocyanine dye. An orthopedic surgeon performed a medial parapatellar arthrotomy and introduced an 18-gauge needle 1-2 cm proximal to the palpated adductor tubercle angled posteromedially. Needle position and dye spread were fluoroscopically documented.

RESULTS: This technique consistently reached the infrapatellar branch of the saphenous nerve, nerve to the vastus medialis muscle, and posterior capsule, with minimal proximal dye spread.

CONCLUSIONS: This …

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. …

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 …