Chemical Actions and Uses Commons^™

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 …

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 …

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.

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 …

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 …

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 …

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 …

Effects Of Neoadjuvant Immunotherapy On Hearing In Patients With Head And Neck Squamous Cell Carcinoma, Bryce Hambach, Anhelina Bilokon, John Lee, L. Noelle Allemang, Jennifer Chisholm, Chris K. Zalewski, Julie Christensen, Carmen C. Brewer, James L. Gulley, Clint T. Allen, Lisa L. Cunningham, Katharine A. Fernandez

SKMC Student Presentations and Publications

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and …

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. …

Utility Of Cenegermin For The Management Of Neurotrophic Keratopathy After Penetrating Keratoplasty, Alexandra R. Zaloga, Ashley Khalili, Brandon D. Ayres, Brenton D. Finklea, Beeran B. Meghpara, Christopher J. Rapuano, Zeba A. Syed

Wills Eye Hospital Papers

BACKGROUND: The study aimed to report the outcomes of patients treated with cenegermin 0.002% for neurotrophic keratopathy (NK) following penetrating keratoplasty (PK).

MATERIALS AND METHODS: This retrospective case series included patients evaluated at a tertiary care hospital who completed an 8-week course of cenegermin for NK within 12 months following PK. The primary outcome measure was NK stage, while secondary outcomes included complete epithelial healing, epithelial defect size, and best-corrected visual acuity (BCVA) at baseline and four time points during and following treatment. We also evaluated disease progression.

RESULTS: Fourteen eyes of 14 patients were included and demonstrated significant improvement …

Supra Inguinal Fascia Iliac Versus Peng Block For Post-Operative Pain Management Of Hip Arthroplasty: A Narrative Review, Shahab Ahmadzadeh, Megan S. Walker, Mary O'Dell Duplechin, Drake P. Duplechin, Charles J. Fox, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Effective post-operative pain management following hip arthroplasty is critical to improving recovery, reducing opioid consumption, enhancing mobility, and reducing the risk of complications for patients. Multimodal anesthesia strategies, including the supra inguinal fascia iliac block (SIFIB) and the periarticular nerve group (PENG) block have become the new point of focus as opposed to traditional methods previously used. This narrative review compares the SIFIB and the PENG block in their efficacy to treat post-operative pain management. Mechanism of action, safety, patient outcomes, and clinical applications are compared between the two blocks for evaluation. Clinical studies have indicated that both blocks reduce …

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 …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Cardiovascular Effects Of Glp-1 Receptor Agonists In Non-Diabetic Adults With Obesity: A Systematic Literature Review, Mariam Abdeen

Rowan-Virtua Research Day

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with obesity. GLP-1 receptor agonists, initially developed for glycemic control in diabetes, are now approved for weight loss in non-diabetic populations. Recent clinical trials suggest these agents may also offer direct cardiovascular benefits.

Objective: This literature review aims to evaluate the cardiovascular effects of GLP-1 receptor agonists, specifically semaglutide, liraglutide, and tirzepatide, in non-diabetic adults with overweight or obesity.

Methods: A systematic search was conducted in January 2025 using PubMed as the primary database, supplemented by Google Scholar and Embase. Clinical trials were selected based on …

Mechanistic Investigation Of Ring-Opening Polymerization Of Polycaprolactone Using Tin(Ii) Catalysts: Ligand Effects And Biomedical Applications, Eva-Larue M. Barber

Honors Scholar Theses

This research explores the mechanistic aspects of ring-opening polymerization (ROP) of ε-caprolactone (CL) to produce polycaprolactone (PCL), a biodegradable polymer widely used in biomedical applications. The study investigates how light exposure and catalyst concentration influence polymerization efficiency, using tin(II) 2-ethylhexanoate [Sn(Oct)₂] as the catalyst in a non-polar toluene solvent at 90 °C. Reactions were conducted under either ambient light or black light bulb (BLB) illumination, with monomer-to-catalyst ratios of 1:1 and 200:1.

Proton nuclear magnetic resonance (¹H NMR) spectroscopy was used to analyze conversion efficiency by tracking the disappearance of monomer signals and appearance of characteristic PCL peaks. Results revealed …

A New Paliperidone Palmitate Formulation: How Is It Different And Where Does It Fit In Our Array Of Choices For Long-Acting Formulations Of Risperidone And Paliperidone?, Justin Faden, Leslie Citrome

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Long-acting injectable (LAI) antipsychotics have been shown to enhance treatment adherence and outcomes in individuals with schizophrenia, schizoaffective disorder, and bipolar disorder. In recent years, the U.S. Food and Drug Administration (FDA) has approved several LAIs with differing amenities of care, such as mode of administration, duration of oral medication supplementation, dosing frequency, needle gauge and size, and injection volume, amongst others. Additionally, several LAIs are distinct formulations of risperidone and paliperidone, making it difficult to distinguish between formulations, and many providers are unfamiliar with these newer agents. In 2024, a once-monthly LAI formulation of paliperidone palmitate, manufactured by Luye …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Management Of Hip Fracture Patients On Direct Oral Anticoagulants: A Survey Of Orthopaedic Trauma Surgeons, Systematic Review, And Meta-Analysis, Clay Spitler, Robert Rutz, Nigel Blackwood, Meghan Wally, Joseph Johnson, Peter Krause, Jaimo Ahn, Zuhair Mohammed, Mark Mcclure, Rebecca Billings, Ziqing Yu, Matthew Yeager

School of Medicine Faculty Publications

OBJECTIVES: This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices. DATA SOURCES: A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications. STUDY SELECTION: Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an "if-reported" basis, …

Beyond Checkpoint Inhibitors: The Three Generations Of Immunotherapy, John Schaub, Shou-Ching Tang

School of Medicine Faculty Publications

Anti-tumor immunotherapy was rediscovered and rejuvenated in the last two decades with the discovery of CTLA-4, PD-1 and PD-L1 and the roles in inhibiting immune function and tumor evasion of anti-tumor immune response. Following the approval of the first checkpoint inhibitor ipilimumab against CTLA-4 in melanoma in 2011, there has been a rapid development of tumor immunotherapy. Furthermore, additional positive and negative molecules among the T-cell regulatory systems have been identified that that function to fine tune the stimulatory or inhibitory immune cells and modulate their functions (checkpoint modulators). Many strategies are being explored to target macrophages, NK-cells, cytotoxic T-cells, …

Residual Traditional Risk In Non-Traditional Atherosclerotic Diseases, Federico Biscetti, Giorgia Polito, Maria Margherita Rando, Maria Anna Nicolazzi, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

Multi-Modal Neo-Adjuvant Anti-Obesity Medications May Be More Effective Than Medically Supervised Weight Loss Or Glp-1 Therapy Alone In Preparing Bmi ≥ 70 Patients For Metabolic Surgery, Michael Kachmar, Florina Corpodean, Iryna Popiv, Kyle B. Lapenna, Denise M. Danos, Michael W. Cook, Brian A. Saunders, Jean J. Domercant, Vance L. Albaugh, Philip R. Schauer

School of Medicine Faculty Publications

Background/objectives: Optimizing patients with a body mass index (BMI) ≥ 70 kg/m² for metabolic surgery (MS) is challenging. However, pre-operative weight loss may be important for improving the safety of MS for these high-risk patients. Multi-modal anti-obesity medications (mmAOM) may enhance preoperative weight loss compared to non-pharmacologic medically supervised weight loss (NP-MSWL) or glucagon-like peptide-1 receptor agonist monotherapy (Mono-GLP-1) alone. Subjects/methods: This retrospective study analyzed 113 patients with BMI ≥ 70 kg/m² at a single metabolic disease treatment institute. Interventions/methods: Patients were categorized into NP-MSWL (n = 13), Mono-GLP-1 (n = 54), and mmAOM (n = 46) groups. The primary …

A Non-Toxic Analgesic Elicits Cell-Specific Genomic And Epigenomic Modulation By Targeting The Pag Brain Region, Hernan A. Bazan, Brian L. Giles, Surjyadipta Bhattacharjee, Scott Edwards, Nicolas G. Bazan

School of Medicine Faculty Publications

Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP's limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, from the periaqueductal gray (PAG) midbrain region, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund's adjuvant (CFA)-induced inflammatory pain …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight …

Takeout Or Delivery? Reoperation Rates In Lower Extremity Long Bone Osteomyelitis Treated With Debridement And Local Antibiotic Delivery Systems, Nolan M. Reinhart, Jackson P. Tate, Jacob S. Budin, Julianna E. Winter, Olivia C. Lee, William F. Sherman

School of Medicine Faculty Publications

BACKGROUND: Early diagnosis and treatment of osteomyelitis is essential to prevent potential complications including sepsis, extensive bone resection, amputation, and death. Despite current treatment strategies for management of osteomyelitis, recurrence rates reported in the literature are upwards of 25 %. Current evidence comparing the efficacy of differing surgical treatments of osteomyelitis is inconclusive. The purpose of this study is to compare rates of re-debridement and amputation in patients who receive either debridement alone or debridement with placement of local antibiotic delivery systems as initial treatment for lower extremity long bone osteomyelitis. METHODS: A retrospective cohort study was performed to investigate …

Beta-Blocker Use In Patients Undergoing Non-Cardiac Surgery: A Systematic Review And Meta-Analysis, Doménica Herrera Hernández, Bárbara Abreu, Tania S. Xiao, Andreina Rojas, Kevin López Romero, Valentina Contreras, Sol Villa Nogueyra, Zulma Sosa, Samantha M. Alvarez, Camila Sánchez Cruz, Ernesto Calderón Martinez

Department of Radiology Faculty Papers

BACKGROUND: The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery.

METHODS: A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; …