Chemicals and Drugs Commons^™

Prenatal Cannabis Exposure Is Associated With Occipitotemporal Brain Surface Area In Neonates, Alexander J. Dufford, Sun Hyung Kim, Martin Styner, Xinyi Shen, Erika Iisa, Marilyn A. Huestis, Peter Fried, Christine Conageski, Jocelyn E. Phipers, Cristina Sempio, Jost Klawitter, Pilyoung Kim, Tessa L. Crume

Institute of Emerging Health Professions Faculty Papers

IMPORTANCE: Prenatal cannabis use has been associated with neurodevelopmental consequences for the offspring beginning in childhood; however, it is unclear if neonatal brain structural morphometry is impacted shortly after birth.

OBJECTIVE: We examined differences in regional surface morphometry among neonates exposed to chronic in utero cannabis compared to unexposed neonates.

DESIGN: The Moms Helping Moms study is a prospective pre-birth cohort selected based on chronic prenatal cannabis use and an unexposed control group. Exclusion criteria included alcohol, tobacco, or other substance use. Participants included in this analysis included 18 mother-neonate pairs with prenatal cannabis exposure and 21 unexposed pairs. Chronic …

Timing Of Isotretinoin Exposure And Early Postoperative Complications After Anterior Cruciate Ligament Reconstruction, Areeb Ahmad, Ronald J. Shamus, Kassem Ghayyad, Daryl C. Osbahr, Adam J. Money, Michael G. Ciccotti, George J. Richard

Rothman Institute Papers

INTRODUCTION: Isotretinoin (ITN) is widely prescribed for severe acne in adolescents and young adults, a population where anterior cruciate ligament reconstruction (ACLR) is commonly performed. Long-standing concerns about impaired wound healing have prompted many surgeons to delay procedures, despite limited orthopaedic-specific evidence. This retrospective case series evaluates early postoperative clinical complications in patients with documented ITN exposure undergoing ACLR.

METHODS: We retrospectively reviewed primary ACLR cases from 2015 to 2025 at a multisite orthopaedic practice with documented ITN exposure within 12 months of surgery and at least 3 months of follow-up. ITN exposure was categorized as perioperative (≤10 days), recent …

An Observational Study Of The Effect Of Concomitant Levetiracetam On Apixaban Concentrations In A Hospital Cohort, Chazmyn Riley, Kevin Lam, Cristina Micale, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the lack of evidence of a mechanism-based drug interaction, some professional organizations have advised caution coadministering apixaban and levetiracetam. Eligible patients taking apixaban with or without levetiracetam for any indication for at least 72 h were screened from the electronic medical records. Plasma samples from 77 patients were retrieved from salvaged clinical blood collections. Apixaban minimum and maximum concentrations (Cmin and Cmax) were compared using descriptive statistics in R. While the median Cmin and Cmax appear to be marginally elevated, there were no apparent differences relative to apixaban alone. These findings suggest no apparent interaction of levetiracetam and support …

Intravenous Versus Oral Tranexamic Acid In Shoulder Arthroplasty, Tarishi Parmar, Akin Adio, Mohammad Daher, Adam Khan, John Horneff, Joseph A. Abboud

Rothman Institute Papers

PURPOSE: Tranexamic acid (TXA) is used in shoulder arthroplasty to reduce blood loss. While intravenous (IV) TXA is standard, oral TXA offers advantages in cost and administration. This study compares 90-day complications and postoperative laboratory values between IV and oral TXA in total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study using TriNetX identified adults undergoing primary TSA (2005-2025) receiving TXA on the day of surgery, stratified by route (IV vs. oral). One-to-one propensity score matching was performed. Ninety-day outcomes included transfusion, thromboembolic events, cardiac and renal complications, neurologic events, infection, wound dehiscence, readmissions, emergency department visits, opioid utilization, and …

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 …

Dabrafenib-Induced Cutaneous Eruptions In A Patient With Langerhans Cell Histiocytosis, Jaanvi Mehta, Julianna Tolotta, Eleanor Matthews, Daniel Joffe, Safiyyah Bhatti, Lauren Banner, Jenna Mandel, Molly Wallace, Timothy G. Webster, Jason B. Lee, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Langerhans cell histiocytosis (LCH) is a rare malignancy marked by clonal proliferation of Langerhans cells, with BRAF V600E mutations identified in over 50% of the cases. BRAF inhibitors (BRAFi), such as dabrafenib, have shown efficacy in treating BRAF V600E-mutant LCH. However, BRAFi therapy is associated with cutaneous adverse effects, including the development of new melanocytic nevi, verrucae, and keratinocyte carcinoma (KC). This case report describes a 78-year-old woman with BRAF V600E-mutant LCH who developed multiple dermatologic side effects following dabrafenib salvage therapy. Seven weeks into treatment, the patient presented with eruptive palmoplantar nevi, verrucae, and a basal cell carcinoma (BCC). …

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 …

Biophysical Insights Into A Cryptic Ligand Site In The Hydrophobic Core Of Human Pcna, Alexis N. Dispensa, Sharon N, Greenwood, Jason Yang, Daniel E. Logatto, James Fusco, E. Railey White, Roderic G. Eckenhoff, Zhiwei Liu, Brian P. Weiser

Department of Anesthesiology Faculty Papers

Proteins contain small pockets that form due to imperfections in residue packing or the rotational and conformational movement of amino acids. In this work, we used the fluorescent probe 1-aminoanthracene (AMA) to detect a small ligand pocket in the hydrophobic core of human proliferating cell nuclear antigen (PCNA), which is a critical protein for DNA replication and repair. Fluorescence measurements of AMA reported that the core of PCNA had a dielectric constant (ε) of 4, which was very apolar and similar to cyclohexane (ε = 2). Protein mutagenesis, photoaffinity labeling, and molecular dynamics simulations localized the binding site for AMA …

Tranexamic Acid In High-Risk Shoulder Arthroplasty Patients: Safety Across Thromboembolic, Cardiac, Renal, And Neurologic Risk Profiles, Tarishi Parmar, Akin Adio, Asim Handy, Mohammad Daher, Alec Kellish, Adam Khan, Joseph A. Abboud

Rothman Institute Papers

INTRODUCTION: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements in shoulder arthroplasty. However, concerns regarding thromboembolic, neurologic, cardiac, and renal complications have limited its use in medically high-risk patients. This study evaluated temporal trends and the safety of TXA in high-risk patients undergoing total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study was conducted using TriNetX, identifying patients who underwent shoulder arthroplasty (2012-2025). Patients were stratified by preexisting high-risk conditions, including prior thromboembolism, renal failure, atrial fibrillation, seizure disorders, and visual disturbances. Within each subgroup, patients receiving TXA were propensity score-matched to those who did not. Perioperative TXA …

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, …

Symmetrical Drug-Related Intertriginous And Flexural Exanthema Associated With Tirzepatide, William Goodman, Karan Pandher, Mahaa Ayub

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

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 …

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 …

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 …

Mutations Altering The Dna Binding Domains Of The Human Rad52 Protein Exert Distinct Effects On Homologous Recombination Repair In Saccharomyces Cerevisiae, Glenn M. Manthey, Elise W. Wolf, Jason Xu, M. Cristina Negritto, Renee A. Bouley, Ruben C. Petreaca, Adam M. Bailis

College of Health Professions Faculty Papers

RAD52 is a conserved member of the homologous recombination repair (HRR) apparatus from yeast to humans. Mutating conserved amino acids in the internal and external DNA binding domains of the human RAD52 protein (HsRAD52) has discrete effects in vitro. Previous studies have shown that HsRAD52 supports multiple mechanisms of HRR in budding yeast, suggesting the utility of this model system for exploring the correspondence between losses of HsRAD52 function in vitro and their impact in vivo. We report that disrupting the internal and external DNA binding domains of HsRAD52 produced distinct effects on the repair of genomic DNA double-strand breaks …

Controlled Antibiotic Release From Emulsion-Loaded Alginate And Fibrin Hydrogels Using Ultrasound, Ziba Ghareh Nazi Fam, Asia Winslow, Mario Fabiilli, Sam Varghese, Brian Oeffinger, Flemming Forsberg, Noreen Hickok, Lauren Delaney

Department of Radiology Faculty Papers

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and …

Cancer Vaccine Targeting Mutated Gnaq-Expressing Uveal Melanoma, Vitali Alexeev, Mizue Terai, Sergei Koshkin, Olga Igoucheva, Takami Sato

Department of Medical Oncology Faculty Papers

Background/Objectives: Uveal melanoma (UM) is the most common intraocular malignancy in adults. Although brachytherapy of the primary tumor provides an approximate 80% five-year survival, with time, nearly half of patients experience predominant liver metastases. It was proposed that malignant cells migrate early and stay dormant as they adapt to the liver microenvironment. We propose that cancer vaccine-mediated activation of UM-targeted immunity in primary UM patients could prevent progression of metastatic disease from dormant cells or malignant seeds. Thus, this study explored DNA vaccination as a measure to educate the immune system to recognize the most common UM-associated Q209L tumor driver …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Optimal Murine Cd4+ T Cell Priming By Mrna-Lipid Nanoparticle Vaccines Requires Endogenous Antigen Processing, Julia E. Rood, Suh Kyung Yoon, Mary K. Heard, Stephen D. Carro, Emma J. Hedgepeth, Mary E. O'Mara, Michael J. Hogan, Nhu Le, Hiromi Muramatsu, Kieu Lam, Petra Schreiner, Coral Kasden, Hansell H. Stedman, Ryan A. Langlois, James Heyes, Norbert Pardi, Laurence C. Eisenlohr

College of Life Sciences Faculty Papers

Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4+ T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine specific CD4+ T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results …

Selective Deletion Of Slc2a1 From The Rpe Reveals That Rods But Not Cones Depend On Glucose Transport Across The Outer Blood-Retinal Barrier, Lauren L. Daniele, John Y.S. Han, Minzhong Yu, Ravi A. Sangani, Craig D. Beight, Cyrus Rostami, Philip D. Kiser, Neal S. Peachy, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. …

Disease Burden Of Asthma Patients Utilizing Short-Acting Beta-2 Agonist-Only Inhalers As Rescue In The United States, Njira Lugogo, Rena C. Moon, Yen Chung, Joy David, Omar Motawakel, Ning A. Rosenthal, Neil Skolnik

Department of Family & Community Medicine Faculty Papers

Purpose: We aimed to describe the disease burden of asthma and examine relationships between short-acting beta-2 agonist (SABA) use and asthma exacerbations. Patients and Methods: This retrospective cohort study used geographically diverse Premier Healthcare Database (PHD) and linked insurance claims (10/01/2021-09/30/2022) for US patients aged ≥18 years with a SABA-only prescription and a history of asthma exacerbation within 12 months before index date (the earliest SABA prescription date). Three asthma control groups were defined based on SABA usage: well controlled-low (0–1 prescriptions), not well controlled-medium (2–3 prescriptions), very poorly controlled-high (≥4 prescriptions). Four asthma severity groups were defined using asthma …

Defining Rna Oligonucleotides That Reverse Deleterious Phase Transitions Of Rna-Binding Proteins With Prion-Like Domains., Lin Guo, Jacob Mann, Jocelyn Mauna, Katie Copley, Hejia Wang, Jack Rubien, Cristian Bergmann, Jenny Carey, Jessica Merjane, Marilyn Ngo, Jiazhen Xu, Hana Odeh, Jiabei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin Kim, Anastasia Murthy, Tapas Paul, Bede Portz, Amanda Gleixner, Zamia Diaz, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric Huang, Alessandra Chesi, Nicolas Fawzi, Sua Myong, Christopher Donnelly, James Shorter

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs that prevent FUS fibrillization by promoting liquid phases and distinct short RNAs that prevent and reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. We define a short RNA that dissolves cytoplasmic FUS aggregates, restores nuclear FUS, and mitigates FUS toxicity in optogenetic models and ALS …

A Phase 1, First-In-Human, Dose Escalation Study Of Jnj-80038114, A Psmaxcd3 Bispecific Antibody, In Participants With Metastatic Castration-Resistant Prostate Cancer, Andrew Hudson, Anuradha Jayaram, Benjamin Garmezy, Nicholas Zorko, Kevin Zarrabi, Ligi Mathews, Brent Rupnow, Mengjie Li, Debopriya Ghosh, Karen Urtishak, Peter Francis, Sherry Wang, Edward Attiyeh, Johann De Bono

Department of Medical Oncology Faculty Papers

PURPOSE: Prostate-specific membrane antigen (PSMA) has been identified as a therapeutic target for metastatic castration-resistant prostate cancer (mCRPC). The recent success of radioligands targeting PSMA spurred development of new PSMA-targeting agents including immunotherapy. JNJ-80038114 is a bispecific antibody that binds PSMA on tumor cells and CD3 on T cells to induce anti-tumor activity.

METHODS: This was a phase 1, open-label, multicenter study of JNJ-80038114 in participants with mCRPC and ≥ 1 prior systemic therapy. JNJ-80038114 was administered subcutaneously every 3 weeks (Q3W), starting at 0.1 mg. The primary endpoint was safety. Secondary endpoints included pharmacokinetics (PK), immunogenicity, and prostate-specific antigen …

Safety And Tolerability Of Single And Multiple Daily Oral Doses Of Dried Kratom Leaf Powder In A Randomized Trial In Healthy Volunteers, Marilyn A. Huestis, John Bothmer, Thomas Hudzik, Jack E. Henningfield, Sibyl Swift

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Kratom use is rising, increasing the need for safety and tolerability studies of high-quality and well-characterized kratom products in humans. Kratom's risk-benefit ratio, recommended dose, treatment-emergent adverse events (TEAEs), abuse potential, and withdrawal require evaluation. Thus, the safety and tolerability of 4 escalating single and 15 daily dried kratom leaf powder doses in human volunteers were evaluated over 47 days in the largest controlled kratom-administration study to date.

METHODS: A randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of MitraLeaf kratom powder after single doses (SD), during 15 daily doses (multiple doses; MD), and a 23-day follow-up was conducted in 116 …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

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 …

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

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 …