Chemical Actions and Uses Commons^™

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker

SPARK Symposium Presentations

The growing threat of antimicrobial resistance (AMR) has and will contribute to global economic and public health concerns in the foreseeable future leading into 2050. As mortality rates derived from AMR are projected to reach 10 million if no viable solution is found to combat it through hastened drug discovery. The use of natural products to mitigate AMRs effects is viable as more than 50% of FDA approved drugs are natural products. These natural products are synthesized by biosynthetic gene clusters (BGC), found in bacteria with a regulatory protein not allowing transcription until unbound . Current methods of eliciting the …

A Phase Ii Trial Of Defactinib Combined With Avutometinib In Patients With Metastatic Uveal Melanoma, Rino S. Seedor, Mizue Terai, Sergei A. Koshkin, Andrew E. Aplin, Marlana Orloff, Erin Sharpe-Mills, Madeleine Naccarato, Aurora Mills, Alfredo A. Molinolo, J. Silvio Gutkind, Takami Sato

Kimmel Cancer Center Faculty Papers

Background: Treatment options are limited, and outcomes remain poor for patients with metastatic uveal melanoma (MUM). We conducted an investigator-initiated, prospective, single-arm, single-institution, phase II study evaluating the combination of an FAK inhibitor (defactinib) with a RAF/MEK inhibitor (avutometinib) for the treatment of MUM. Methods: From February 2021 through January 2023, 12 patients with MUM were treated with the combination of defactinib and avutometinib. Defactinib was given 200 mg twice daily, and avutometinib was given 3.2 mg twice a week. Both drugs were given for 3 weeks on and 1 week off (28-day cycle). Disease control rate was the primary …

Exceptional Response Of Radiotherapy-Naïve Cranial Meningiomas To Dual Immune Checkpoint Blockade In Bap1 Tumor Predisposition Syndrome, Gary Gallia, Christine Hann, Calixto-Hope Lucas, Licia Pacheco Luna, David Kamson, Takami Sato

Department of Medical Oncology Faculty Papers

Meningiomas are the most common primary central nervous system tumors, and while most are benign, atypical and anaplastic variants frequently recur and have limited effective treatment options. Recent trials of PD-1 blockade in unselected meningioma cohorts have demonstrated modest activity, with low objective response rates. These findings highlight the need to identify molecular biomarkers that may predict immunotherapy sensitivity in this disease. BRCA1-associated protein 1 (BAP1) is a tumor suppressor critical for chromatin regulation and DNA repair, and germline pathogenic variants cause BAP1 tumor predisposition syndrome (BAP1-TPDS), a hereditary cancer syndrome characterized by uveal melanoma, mesothelioma, renal cell carcinoma, meningioma, …

Neurodevelopmental Effects Associated With In Utero Exposure To Bpa, Maximilian A. Nilsen, Grace A. Carlucci, Cody V. Thompson, Berfin Gul

Student Work

No abstract provided.

Structural Basis Of Anthocyanin-Mediated Modulation Of Il-2, Il-17, And Tnf-Α: A Docking And Molecular Dynamics Study, Andrey Bogoyavlenskiy, Adolat Manakbayeva, Timur Kerimov, Igor Yershov, Madina Alexyuk, Pavel Alexyuk, Vladimir Berezin, Vyacheslav Dushenkov

Publications and Research

Anthocyanins are naturally occurring flavonoid pigments widely distributed in plants and are recognized for their antioxidant and anti-inflammatory activities. However, the molecular mechanisms underlying their potential immunomodulatory effects remain poorly characterized, particularly regarding their direct interactions with key signaling cytokines. In this study, a set of selected anthocyanins was investigated using a hierarchical computational workflow targeting three major pro-inflammatory cytokines: interleukin-2 (IL-2), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Molecular docking analyses identified primulin and antirrhinin as the most favorable binders, forming stabilizing hydrogen bonds and hydrophobic interactions within predicted cytokine interaction interfaces. To further assess the stability of these …

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …

Infectious Retinitis Associated With Jak Inhibitors: The Ongoing Duality Of Jak Inhibitors, Jose S. Pulido, Fukutaro Mano, Marcello Casella, Susumu Ishida

Wills Eye Hospital Papers

PURPOSE: To discuss the recent evidence that Janus kinase (JAK) inhibitors can cause viral retinitis.

METHODS: A commentary on the case report in this issue and a review of cases in the literature.

RESULTS: A total of 6 cases have now been reported of cytomegalovirus retinitis associated with Jak inhibitors. Additionally, there was a case of bilateral toxoplasma retinitis and a case of herpetic scleritis.

DISCUSSION: It is important to be aware of the potential blinding complications associated with JAK inhibitors and if the patient complains of acute vision loss and/or floaters, the patient should be emergently referred to a …

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group

School of Medicine Faculty Publications

Background Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea. Methods In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by …

Cocaine Upregulates Microglial Lipid Droplet Formation Through Increasing Lipid Synthesis Activity In Vitro And In Vivo, Yan Cheng, Brooke Russell, Liam Liyang Guo, Aryan Patel, Yan Y. Sanders, Ming-Lei Guo

Department of Biomedical and Translational Sciences Faculty Publications

A novel subtype of microglia, lipid droplet accumulation microglia (LDAMs), has been identified in the aged brain, which is characterized by sustained inflammation and senescent-like phenotypes. LDAMs are deeply involved in promoting brain aging as well as the pathogenesis of multiple neurodegenerative diseases. Cocaine can alter brain lipidomic profiles, induce microglial activation, and accelerate brain aging. This suggests that cocaine might affect microglial lipid metabolism, which ultimately aggravates aging-related neurological disorders in people with addictions. In this study, we explored the effects of cocaine on microglial lipid metabolism. Our results showed that chronic cocaine administration altered brain lipid profiles and …

Tramadol For Treatment Of Neurogenic Cough: A Retrospective Case Series, Benjamin Joseph Rubinstein, Sheela Saidha, John Todd Sinacori

Department of Otolaryngology (ENT) Faculty Publications

Objectives

Explore the efficacy of tramadol for neurogenic cough and describe the longitudinal treatment experience.

Methods

A retrospective case series of adults with chronic cough who were treated with tramadol for neurogenic cough. A complete response was defined as no pathologic coughing, and a partial response was defined as 50% or greater reduction in severity or frequency.

Results

Sixty-nine patients were included. 38% of patients reported a complete response with an additional 33% reporting a partial response. The most common successful dosing regimen was 50 mg BID. Age, gender, and BMI did not impact treatment response. Patients with a history …

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

Vasoactive Drug Use In Children With Community Acquired Septic Shock In Australia And New Zealand, Elliot Long, Stephen Hearps, Amanda Williams, Ben Gelbart, Warwick Butt, Thomas Rozen, Sarah Mcnab, Meredith Borland, Simon Erickson, Shefali Jani, Marino Festa, Eunicia Tan, Natalie Phillips, Sainath Raman, Amit Kochar, Subodh Ganu, Simon Craig, Anna Lithgow, Arjun Rao, Emma Whyte, Stuart Dalziel, Shane George, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Franz Babl

Department of Medicine Faculty Papers

BACKGROUND: Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis.

METHODS: Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-< 18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected.

FINDINGS: 6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall …

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

Pathways And Challenges In The Clinical Translational Of Radiopharmaceuticals For Pediatric Investigations, Erik Stauff, Hanieh Karimi, Heidi H. Kecskemethy, Thomas H. Shaffer, Reza Vali, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical development and clinical translation face numerous scientific, ethical, and regulatory challenges, particularly within the pediatric population. Although molecular imaging holds significant promise for improving diagnosis and treatment across a spectrum of diseases, including pediatric-specific conditions like Kawasaki disease, autism spectrum disorders, attention-deficit/hyperactivity disorder, and neuroblastoma, the path from discovery to clinical application remains problematic. The U.S. Food and Drug Administration (FDA) provides three primary pathways-traditional Investigational New Drug (IND) applications, exploratory Investigational New Drug application (eIND), and the Radioactive Drug Research Committee (RDRC) mechanism-to facilitate clinical translation of radiotracers. However, these frameworks are not specifically tailored to pediatric needs. …

Managing Anticoagulation In A Patient With Calciphylaxis And Mechanical Valve: A Therapeutic Dilemma, Qutaiba Qafisheh, Abdalhakim Shubietah, Mohanad Qwaider, Muath A. Baniowda, Abdalrahman Assaassa, Roaa Aljunaidi, Abubakar Nazir

Division of Cardiology Faculty Papers

BACKGROUND: Calciphylaxis is a rare, life-threatening vasculopathic syndrome most commonly seen in end-stage renal disease (ESRD) and associated with high mortality. Vitamin K antagonists complicate management in patients with mechanical valves by potentially exacerbating vascular calcification while remaining essential for thromboprophylaxis.

CASE PRESENTATION: A 50-year-old woman with ESRD on hemodialysis and a mechanical mitral valve on warfarin presented with severe abdominal pain and rapidly progressive necrotic ulcers. Despite broad-spectrum antibiotics and sodium thiosulfate, lesions worsened. Biopsies were nondiagnostic; however, the clinical phenotype was consistent with calciphylaxis. A multidisciplinary team transitioned anticoagulation from warfarin to subcutaneous unfractionated heparin (UFH) (333 U/kg …

Hydralazine Inhibits Cysteamine Dioxygenase To Treat Preeclampsia And Senesce Glioblastoma, Kyosuke Shishikura, Jiasong Li, Yiming Chen, Nate R. Mcknight, Thomas P. Keeley, Katelyn A. Bustin, Eric W. Barr, Snehil R. Chilkamari, Mahaa Ayub, Sun Woo Kim, Zongtao Lin, Ren-Ming Hu, Kelly Hicks, Xie Wang, Donald M. O'Rourke, J. Martin Bollinger, Zev A. Binder, William H. Parsons, Kirill A. Martemyanov, Aimin Liu, Megan L. Matthews

SKMC Student Presentations and Publications

Hydralazine (HYZ), a treatment for preeclampsia and hypertensive crisis, is listed by the World Health Organization as an essential medicine. Its mode of action has remained unknown through its seven decades of clinical use. Here, we identify 2-aminoethanethiol dioxygenase (ADO), a key mediator of targeted protein degradation, as a selective HYZ target. The drug chelates ADO's metallocofactor and can alkylate one of its ligands. The resultant inactivation stabilizes regulators of G protein signaling (RGS4 and RGS5) that ADO normally marks for proteolysis, explaining the drug's vasodilatory activity and comporting with observations of diminished RGS levels in both clinical preeclampsia and …

Large Language Models As Information Providers For Appropriate Antimicrobial Use: Computational Text Analysis And Expert-Rated Comparison Of Chatgpt, Claude And Gemini, Marcello Di Pumpo, Maria Rosaria Gualano, Danilo Buonsenso, Francesca Raffaelli, Daniele Donà, Vittorio Maio, Patrizia Laurenti, Walter Ricciardi, Leonardo Villani

College of Population Health Faculty Papers

OBJECTIVES: Antimicrobial resistance is a critical public health threat. Large language models (LLMs) show great capability for providing health information. This study evaluates the effectiveness of LLMs in providing information on antibiotic use and infection management.

METHODS: Using a mixed-method approach, responses to healthcare expert-designed scenarios from ChatGPT 3.5, ChatGPT 4.0, Claude 2.0 and Gemini 1.0, in both Italian and English, were analysed. Computational text analysis assessed readability, lexical diversity and sentiment, while content quality was assessed by three experts via DISCERN tool.

RESULTS: 16 scenarios were developed. A total of 101 outputs and 5454 Likert-scale (1-5) scores were obtained …

Targeting The Bcl2 Family: Advances And Challenges In Bh3 Mimetic-Based Therapies, Nabanita Mukherjee, James Sheetz, Yiqun Shellman

Student Papers, Posters & Projects

The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved significant clinical success, particularly in hematologic malignancies. However, several challenges remain, including resistance mechanisms, toxicity (such as MCL1 inhibitor-associated cardiotoxicity), and the intricate balance between apoptotic and non-apoptotic functions. This review provides a comprehensive overview of BCL2 family biology, the development and clinical application and outcomes of BH3 mimetics, and the emerging resistance mechanism known as double-bolt …

Glucagon-Like Peptide 1 Receptor Agonists And The Clinical Outcomes Of Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Ahmed B. Bayoumy, Lindsay M. Clarke, Parakkal Deepak, Aakash Desai, Priya Sehgal, Uri Gorelik, Haggai Bar-Yoseph, Marie Villumsen, Chris J. J. Mulder, Dirk J. Stenvers, Maarten E. Tushuizen, Nanne K. H. De Boer

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery, and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD.

METHODS: A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to March 15, 2025. Studies reporting outcomes …

A Plain Language Summary Publication Of Patients’ Survival With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel, Matthew A. Powell, Line Bjørge, Lyndsay Willmott, Zoltán Novák, Destin Black, Lucy Gilbert, Sudarshan Sharma, Giorgio Valabrega, Lisa M. Landrum, Martina Gropp-Meier, Ashley Stuckey, Ingrid Boere, Michael A. Gold, Yakir Segev, Sarah E. Gill, Christine Gennigens, Alexandra Sebastianelli, Mark S. Shahin, Bhavana Pothuri, Bradley J. Monk, Joseph Buscema, Robert L. Coleman, Brian M. Slomovitz, Kari L. Ring, Thomas J. Herzog, Morad Marco Balas, Matthew Grimshaw, Shadi Stevens, Dominic W. Lai, Carolyn Mccourt, Mansoor Raza Mirza

Abington Jefferson Health Papers

What is the purpose of this PLS-P? The purpose of this plain language summary of publication is to help you understand recent findings from Part 1 of the RUBY study (full name ENGOT-EN6/GOG3031/RUBY trial). • Researchers sometimes study new combinations of already approved individual treatments to see if the combinations work well together and if they are safe to prescribe to patients. • In Part 1 of the RUBY study, the combination of dostarlimab with carboplatin-paclitaxel was investigated to see how well it worked for patients with primary advanced or recurrent endometrial cancer when compared with patients who were given …

Comparison Of Authentic Urine N-Ethylpentedrone Metabolites To Predicted In Silico And In Vitro Human Hepatocyte Metabolism, Gloria Daziani, Omayema Taoussi, Diletta Berardinelli, Giulia Bambagiotti, Marilyn A. Huestis, Francesco P. Busardò, Jeremy Carlier

Institute of Emerging Health Professions Faculty Papers

Synthetic cathinones are the second most common class of substances belonging to the category of new psychoactive substances (NPS). N-ethylpentedrone (NEPD) self-administration was reported, making it important to elucidate its metabolic pathway to improve its detection. NEPD is often taken together with other substances; confidently identifying its intake is important for accurate toxicological analysis and understanding its toxicity. NEPD metabolism was studied following incubation with human hepatocytes and analysis by liquid chromatography-high-resolution mass spectrometry paired with Compound Discoverer software (Thermo Fisher Scientific). Prediction of possible metabolites was performed with the online software GLORYx. In vivo NEPD metabolism was evaluated by …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

In-Hospital Exposure And Opioids Prescribed After Total Knee Arthroplasty, Clifton Daigle, Robert Branstetter, Leland Van Deventer, Ravi Rajendra, Claudia Leonardi, Amy Bronstone, Vinod Dasa

School of Medicine Faculty Publications

BACKGROUND: Opioids are frequently used intraoperatively and during postanesthesia care unit care in total knee arthroplasty (TKA) cases and are commonly prescribed after surgery despite known adverse effects. This study examined whether in-hospital opioid exposure is related to postoperative opioid prescribing in opioid-naïve TKA patients. METHODS: This retrospective study included opioid-naïve patients (no opioid prescriptions filled during the three months before TKA) who had unilateral primary TKA between May 1, 2020, and November 30, 2023, performed by an orthopaedic surgeon. All patients were treated using the same multimodal pain protocol. Opioid prescriptions filled by patients during the three months following …

Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.

METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …

Current Mechanobiological Pathways And Therapies Driving Spinal Health, Rahul Kumar, Kyle Sporn, Harlene Kaur, Akshay Khanna, Phani Paladugu, Nasif Zaman, Alireza Tavakkoli

SKMC Student Presentations and Publications

Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can …

The Impact Of Different Antidiabetic Drugs On Fracture Risk In Patients With Type 2 Diabetes Mellitus: A Systematic Review And Network Meta-Analysis Of Randomized Controlled Trials With A Focus On Sglt2 Inhibitors, Bushra Admani, Fizza Z. Raza, Fatima Siddiqui, Muhammad T. Ashraf, Muhammad K. Khan, Ifra Habib, Ayesha Usman, Bareeha Mansoor, Zaira Nadeem, Rana J. Ghaffer, Muhammad Riyyan, Sawaira Sajid, Muhammad H. A. Chania, Mahnoor Saleem, Saad Javaid, Nikhil Duseja, Hussam Al Hennawi, Sunita Lakhani

Abington Jefferson Health Papers

SGLT2 inhibitors are a new class of antidiabetic drugs that have shown cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, their effects on fracture risk are unclear and may depend on the type and duration of treatment. This meta-analysis compares the fracture risk of different antidiabetic drugs, including SGLT2 inhibitors, based on data from randomized controlled trials (RCTs). We searched 4 databases for RCTs that reported fracture events in patients with T2DM who received different antidiabetic drugs. We included 117 RCTs that compared 9 types of antidiabetic drugs: SGLT2 inhibitors, DPP-4 inhibitors, α-glucosidase inhibitors, …

Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen

Department of Medical Oncology Faculty Papers

Nasopharyngeal carcinoma (NPC) is a cancer arising from the epithelial cells of the nasopharynx, which is rare in Western countries but extremely prevalent in Borneo and the Southern China region. Present-day hurdles in NPC treatment that lead to poor quality of life and poor survival include distant metastasis and resistance to chemoradiotherapy. Silvestrol and its 5'''-epimer, episilvestrol, are compounds isolated from the plant Aglaia stellatopilosa, which is endemic to Borneo. Silvestrol, a protein synthesis inhibitor, preferentially inhibits the translation of cancer-associated mRNAs. CX-5461 is an inhibitor of RNA polymerase I that catalyzes rRNA synthesis. The present study sought to …