Therapeutics Commons^™

Predictors Of Final Visual Outcome In Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy, Robert C Sergott, Valerio Carelli, Nancy Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni

Wills Eye Hospital Papers

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.

METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.

RESULTS: In 113 eyes treated at least 6 months after disease onset, the …

Optimizing Stereotactic Intracranial Neoplasm Treatment: A Systematic Review Of Pet Integration With Gamma Knife Radiosurgery, Robert C. Subtirelu, Eric M. Teichner, Milo Writer, Kevin Bryan, Shiv Patil, Talha Khan, Lancelot Herpin, Raj N. Patel, Emily Christner, Chitra Parikh, Thomas Werner, Abass Alavi, Mona-Elisabeth Revheim

SKMC Student Presentations and Publications

OBJECTIVE: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and the post-GKRS applications of PET for patient care.

METHODS: PubMed, Scopus, and ScienceDirect were searched in order to assemble relevant studies regarding the uses of PET in conjunction with GKRS for ICN treatment. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to identify relevant studies on the use of PET in conjunction with …

First-In-Human Phase I Open-Label Study Of The Anti-Tim-3 Monoclonal Antibody Incagn02390 In Patients With Select Advanced Or Metastatic Solid Tumors, Martin E. Gutierrez, Shou Ching Tang, John D. Powderly, Ani S. Balmanoukian, Paul E. Hoyle, Zhiwan Dong, Lulu Cheng, Xiaohua Gong, John E. Janik, Nawel Bourayou, Omid Hamid

School of Medicine Faculty Publications

Background T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is an immune checkpoint receptor upregulated during anti-programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy for cancer. TIM-3 blockade may improve the antitumor activity of PD-1/PD-L1inhibition. This phase 1 study evaluated INCAGN02390, a novel, fully human Fc-engineered antibody against TIM-3. Methods INCAGN02390 was evaluated by dose escalation at 10-1600 mg infused in 14-day cycles (every 2 weeks [Q2W]) in pretreated patients with select advanced/metastatic immunogenic solid tumors. Objectives included evaluation of safety/tolerability and maximum tolerated dose (MTD) (primary), pharmacokinetics, preliminary antitumor activity, pharmacodynamics, and immunogenicity (secondary). Results Forty patients were enrolled and …

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Seeking Into Cell-Free Therapies For Bone-Affected Lysosomal Storage Disorders, Andrés Felipe Leal, Harry Pachajoa, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as …

Single-Level Anterior Cervical Discectomy And Fusion Is Associated With Higher Nonroutine Discharge Rates Compared To Cervical Disc Arthroplasty In Obese Patients, Paul G. Mastrokostas, Luke B. Schwartz, Eli Berglas, Aaron B. Lavi, Leonidas E. Mastrokostas, Jonathan Dalton, Christopher K. Kepler, Arya Varthi, Jad Bou Monsef, Afshin E. Razi, Mitchell K. Ng

Rothman Institute Papers

CONTEXT: Obesity is a recognized risk factor for adverse outcomes in cervical spine surgery. While cervical disc arthroplasty (CDA) has emerged as an alternative to anterior cervical discectomy and fusion (ACDF), comparative outcomes among obese patients remain underexplored.

AIMS: The aim of this study is to compare nonroutine discharge rates and other postoperative outcomes between obese patients undergoing single-level ACDF and CDA.

SETTINGS AND DESIGN: Retrospective cohort study using a national database.

SUBJECTS AND METHODS: The National Inpatient Sample was queried to identify obese patients who underwent single-level ACDF or CDA between 2016 and 2020. Inclusion and exclusion criteria were …

Systemic Exogenous Progestins With Or Without Estrogens Are Associated With Decreased Rates Of Venous Procedures For Varicose Veins, Paarth Jain, Adam M. Ostrovsky, Paul J Dimuzio, Luis H. Eraso, Michael Nooromid, Dawn Salvatore, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVES: Risk factors for varicose veins (VVs) such as female sex, pregnancy, and obesity are high estrogen states, yet the role of systemic progestins with or without estrogens (SPEs) in VV management is not well characterized. This study investigates how SPE use affects rates of venous procedures for patients with VV.

METHODS: The TriNetX database was queried for subjects with International Classification of Diseases, 10th edition, diagnoses of asymptomatic VV, chronic venous insufficiency, and complicated VV (inflammation or ulceration). Patients were divided into a control cohort with no subsequent SPE use, a progestin-only cohort, and a combined estrogen-progestin (CEP) cohort. …

Topical Lifitegrast Therapy For Dry Eye Disease, Lama Assi, Salim C. Lutfallah, Tsz Wing Yim, Su Hsun Liu, Sharon J. Duffy, Jayne Weiss

School of Medicine Faculty Publications

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effectiveness and safety of topical lifitegrast therapy alone or in combination with artificial tears, compared with a placebo, artificial tears alone, or no treatment for dry eye disease.

Economic Value Of Intra-Articular Knee Oa Therapies: A U.S. Perspective, Vinod Dasa, Wilson Ngai, Kevin Steele, Ronald Preblick, Heather Watson, Kevin L. Ong

School of Medicine Faculty Publications

AIMS: This study compared the six-month medical/pharmacy costs and healthcare resource utilization (HCRU) for knee OA patients undergoing intra-articular therapy with different classes of hyaluronic acid (HA) (by molecular weight) or corticosteroid (ICS). MATERIALS AND METHODS: Patients across high molecular weight (HMW) HA, medium molecular weight (MMW) HA, low molecular weight (LMW) HA, and ICS therapy groups were matched from a U.S. claims database (Optum's de-identified Clinformatics Data Mart Database), with a final size of 6,234 patients per group. Adjusted six-month medical/prescription costs per patient per month (PPPM), and HCRU rates and costs, were determined. Secondary endpoints included complication rates …

Cardiovascular Health In Cardiac Rehabilitation: Applying The American Heart Association Life's Simple 7 Framework In A Center-Based Cohort, Audry Chacin-Suarez, Tomoaki Hama, Matthew P. Johnson, Helayna Abraham, Thomas P. Olson, Laprincess C. Brewer

Einstein Health Papers

BACKGROUND: Cardiac rehabilitation (CR) is a comprehensive secondary cardiovascular disease program with structured lifestyle interventions to reduce morbidity and mortality. The American Heart Association cardiovascular health (CVH) framework measures health-promoting behaviors and clinical factors, but it has not been rigorously evaluated in the CR setting.

METHODS: This retrospective cohort study analyzed patients attending CR from January 2018 to September 2020. Patients were evaluated at baseline (pre-CR) and completion (post-CR) using 3 clinical factors (blood pressure, cholesterol, and hemoglobin A1c) and 4 health behaviors (smoking, body mass index, physical activity, and diet). CVH score was computed as a composite of each …

Brivaracetam For Spinal Cord Injury-Related Neuropathic Pain: Results Of A Pilot Double-Blinded, Randomized, Placebo-Controlled Clinical Trial, Leslie R. Morse, Ricardo A. Battaglino, Nguyen Nguyen, Brian Devries, Abigail Welch, Ana Lucia Battaglino, Clas Linnman, Michael Stillman, Robert Wudlick, Joda Glossner, Grant Anderton, Richard Goldstein, Scott P. Falci

Department of Medicine Faculty Papers

OBJECTIVE: Assess feasibility, safety, and tolerability of 3 months of oral brivaracetam for severe (9-10/10) spinal cord injury-related neuropathic pain.

METHODS: We conducted a multisite pilot study where adults were randomized to 3 months of brivaracetam (100 mg BID) or placebo. Pain was assessed via the Brief Pain Inventory, the International Spinal Cord Injury Pain Basic Dataset (version 2.0), and a daily pain diary.

RESULTS: We enrolled 24 participants across 2 sites and 14 participants were included in the final analysis (n = 8 placebo, n = 6 brivaracetam). The drug was tolerated with expected, nonserious side effects (nausea if …

Evaluation Of The Wound Healing And Anti-Microbial Activity Of Hydroethanolic Extracts Of Young And Old Leaves Of Vernonia Amygdalina Delile, Du-Bois Asante, Christian Kweku Adokoh, Elvis Ofori Ameyaw, Desmond Omane Acheampong, Ebenezer Afrifa-Yamoah, Precious Barnes, Gideon Agyeah, Ruben Phillips, Julie Sartori

Research outputs 2022 to 2026

Background: Vernonia amygdalina Delile (VA) has been reported as an important herb for the management of wound in traditional medical settings. However, the evaluation of the wound healing and antimicrobial effect of the young and old leaves of VA is lacking. Objective This study sought to determine the cutaneous wound healing and in vitro anti-microbial activities of the young and old leaf extracts of VA. Methods Mineral elements that aid in wound healing and vitamin C levels were evaluated in the young and old leaves of VA. Phytochemical analysis of the hydroethanolic leaf extracts of the young leaves (HEthYL) and …

The Dubr/Mir-210-5p/Retsat Axis In Cholesterol-Associated Steatohepatitis: Clinical Signatures And Molecular Mechanisms, Hana Mahmoud Abdelzaher

Theses and Dissertations

Metabolic-associated fatty liver disease (MAFLD) represents an increasing global health challenge, with cholesterol-associated steatohepatitis (CASH) emerging as a distinct pathological entity warranting investigation. While CASH demonstrates unique features compared to traditional triglyceride-driven steatohepatitis, its underlying molecular mechanisms remain poorly understood. This study investigates a novel regulatory axis involving DPPA2 Upstream Binding RNA (DUBR), miR-210-5p, and retinol saturase (RETSAT). 170 patient samples revealed progressive axis dysregulation in disease states, with RETSAT emerging as a highly accurate diagnostic marker (AUC=1.000). Using novel in vitro models of MASH and CASH, we demonstrated that miR-210-5p modulation significantly affects lipid accumulation and cellular phenotype, with …

Evaluation Of Aav Vectors With Tissue-Specific Or Ubiquitous Promoters In A Mouse Model Of Mucopolysaccharidosis Type Iva, Shaukat A. Khan, Jose Victor Álvarez, F. N. U. Nidhi, Eliana Benincore-Florez, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis type IVA (MPS IVA) is caused by a deficiency of N-acetyl-galactosamine-6-sulfate sulfatase (GALNS), leading to the accumulation of keratan sulfate and chondroitin-6-sulfate and development of severe skeletal dysplasia. Enzyme replacement therapy and hematopoietic stem cell transplantation are current treatment options but have limited impact on bone lesions. In this study, we investigated adeno-associated virus (AAV)8 or AAV9 vectors with liver-specific thyroxine-binding globulin or liver-specific promoter-a modification of hAAT (LSPX), liver-muscle tandem (LMTP), liver-bone tandem (LBTP), and ubiquitous cytomegalovirus early enhancer/chicken β-actin (CAG) promoters in MPS IVA mice to compare therapeutic efficacy on biochemical markers and bone pathology. All vectors …

Childhood Gastroesophageal Reflux Disease: A Comprehensive Review Of Disease, Diagnosis, And Therapeutic Management, Daniyal Raza, Farhan Mohiuddin, Muhammad Haris Khan, Maheen Fawad, Syed Musa Raza

School of Medicine Faculty Publications

Gastroesophageal reflux disease (GERD) affects both adults and children, although the symptoms differ significantly between these groups. While adults typically experience heartburn and regurgitation, children may present with more subtle signs, such as failure to thrive, chronic cough, wheezing, and Sandifer syndrome. Diagnosing GERD in children necessitates a multifaceted approach due to the diverse symptomatology and challenges in communication. Clinical assessment serves as the cornerstone of diagnosis, supported by tools like pH monitoring, esophageal impedance testing, and upper gastrointestinal endoscopy. Imaging studies, such as barium swallow, can also provide valuable insights into anatomical abnormalities and the extent of reflux. Treatment …

Advances In Molecular Imaging Of Vegfrs: Innovations In Imaging And Therapeutics, Hanieh Karimi, Sarah Lee, Wenqi Xu, Sigrid A. Langhans, David K. Johnson, Erik Stauff, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful …

Tumor Microenvironment Governs The Prognostic Landscape Of Immunotherapy For Head And Neck Squamous Cell Carcinoma: A Computational Model-Guided Analysis, Priyan Bhattacharya, Alban J Linnenbach, Andrew P. South, Ubaldo E. Martinez-Outshoorn, Joseph M. Curry, Jennifer M. Johnson, Larry A. Harshyne, Mỹ G. Mahoney, Adam J. Luginbuhl, Rajanikanth Vadigepalli

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Immune checkpoint inhibition (ICI) has emerged as a critical treatment strategy for squamous cell carcinoma of the head and neck (HNSCC) that halts the immune escape of the tumor cells. Increasing evidence suggests that the onset, progression, and lack of/no response of HNSCC to ICI are emergent properties arising from the interactions within the tumor microenvironment (TME). Deciphering how the diversity of cellular and molecular interactions leads to distinct HNSCC TME subtypes subsequently governing the ICI response remains largely unexplored. We developed a cellular-molecular model of the HNSCC TME that incorporates multiple cell types, cellular states, and transitions, and molecularly …

Comparison Between Pipeline Embolization Device (Ped) Versus Flow Redirection Endoluminal Device (Fred) For Intracranial Aneurysms: A Comprehensive Systematic Review And Meta-Analysis, Seyed Maroufi, Mohammad Fallahi, Muhammad Waqas, Othman Bin-Alamer, Manisha Koneru, Joanna Roy, Jane Khalife, Hamza Shaikh, Daniel Tonetti

Department of Neurosurgery Faculty Papers

OBJECTIVES: The performance of the Pipeline Embolization Device (PED) and relatively newer double-layered Flow Re-Direction Endoluminal Device (FRED) have been studied for the treatment of intracranial aneurysms, but direct comparisons between PED and FRED are limited. The current systematic review aims at comparing the efficacy and safety of PED and FRED.

METHODS: A systematic review of the literature was conducted according to the PRISMA guideline. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched, and related records were identified. A meta-analysis of double-arm studies comparing PED and FRED was conducted on angiographic and clinical outcomes, retreatment rates, and …

Barriers To Clinical Cosmetic And Laser Dermatology Research In The Academic Setting By Source Of Funding: A Systematic Review, Bianca Y. Kang, Saranya P. Wyles, Yakir Levin, Rawaa Almukhtar, Stephanie R. Jackson Cullison, Jayne S. Joo, Sami K. Saikaly, Shalinie Mahadeo, Michael Ong, Sophia Salingaros, Maria Hordinsky, Sarah A. Ibrahim, Devina Mehta, Shoko Mori, Edit B. Olasz Harken, Diana Bolotin, Kira Minkis, Murad Alam

Department of Dermatology and Cutaneous Biology Faculty Papers

Clinical research is a cornerstone of academic dermatology, including research in cosmetic and laser procedures. However, numerous barriers exist to conducting clinical research in an academic setting as compared to private practice. The objective of this study was to describe the barriers to clinical research in cosmetic and laser dermatology in the academic setting under three common funding scenarios: (1) industry sponsored, (2) unfunded, investigator-initiated, and (3) publicly funded, investigator-initiated. A systematic review of the literature was conducted to identify 17 publications regarding funding of clinical dermatology research. Inductive content analysis was used to extract, categorize, and understand the barriers …

Of Dolls And Jewels : Keeping As A Strategy Of Care And Belonging, Yuqi Fan

Masters Theses

In this thesis, I will discuss the psychology behind object attachment in the doll-keeping subculture by integrating doll language into contemporary jewelry. I researched the Chinese term “Pi” as an accurate way of explaining how doll-keepers are attached to their dolls. In this 21st century, the widespread use of social media and AI technologies have deepened people's reliance on virtual spaces, leading to emotional detachment in our society. Adopting the concept of “Pi” into contemporary jewelry, which encourages a shift in focus towards external objects, the practice of doll-keeping becomes a form of self-care that compensates for our current loneliness …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …