Digital Commons Network^™

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R. Rao, Barbara C. Jobst, Jerzy P. Szaflarski, John D. Rolston, Lesley C. Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C. Dugan, David E. Burdette, Angela Y. Peters, Atif Sheikh, Kevin F. Haas, Dileep R. Nair, Lilit Mnatsakanyan, Imran H. Quraishi, Meriem K. Bensalem-Owen, Michael J. Doherty, Babak Razavi, Tiffany L. Fisher, Christopher T. Skidmore, Pradeep N. Modur, Tawnya M. Constantino, Vicenta Salanova, Andrew J. Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W. Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E. Maciver, Sanjay E. Patra, Edward F. Chang, Jon T. Willie, Ryder Gwinn, Travis Stoub, John M. Stern, Tami Crabtree, Cairn G. Seale, Sharon C. Mcfadden, Jacob F. Norman, Lise Johnson, Martha J. Morrell

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Is2c2: A Cointelligent Platform For Mechanistic Discovery Of Disease Cellular Crosstalk, Jianting Sheng, Ju Young Ahn, Li Yang, Zhihao Wan, Shaohua Qi, Xiaohui Yu, Zhan Xu, Yuliang Cao, Matthew Vasquez, Amna Irfan, Yuanyuan Zhu, Hong Zhao, Zheng Yin, Ying Zhu, Yunfeng Ding, Alireza Faridar, Lin Wang, Fengshuo Liu, Hongxia Wang, Zhigang Ji, Dongxue Mao, Michael Chan, Daniel Kermany, Wenjuan Dong, Doo Yeon Kim, Xiang H-F Zhang, Stephen T C Wong

Faculty, Staff and Students Publications

Large language models (LLMs) have demonstrated impressive capabilities in summarization, reasoning, and content generation, yet their inability to directly interpret large-scale omics data has limited their utility in data-driven hypothesis generation-particularly in mechanism discovery that demands the integration and interpretation of multimodal datasets, heterogeneous models, and deep domain expertise. Conversely, traditional computational algorithms excel at quantitative analysis of omics data but often rely heavily on labor-intensive, expert-driven interpretation to extract biologically meaningful insights. Here, we introduce (cointelligent single-cell spatial cell‒cell communication: iS2C2), a novel cointelligent platform that synergizes mathematically rigorous computational algorithms with the contextual reasoning capabilities of LLMs to …

Risk Of Late Recurrence Of Colorectal And Breast Cancer Among Older Long-Term Cancer Survivors., Faiza Yasin, Sarah J. Westvold, Jessica B. Long, Terry Hyslop, Michael Cecchini, Ira Leeds, Andrea Silber, Shi-Yi Wang, Lisa Spees, Rebecca Forman, Tendai Kwaramba, Melissa Taylor, Cary P. Gross, Michaela A. Dinan

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: A growing population of older adult cancer survivors faces competing cancer and noncancer health risks. There are limited real-world data on recurrence patterns beyond 5 years post-treatment.

METHODS: This was a SEER-Medicare retrospective cohort study of patients aged ≥66 with stage I-III breast, colon, or rectal cancer who received definitive surgery and survived ≥5 years from diagnosis without recurrence or second primary malignancy. Late recurrence (5-10 years postdiagnosis) was identified using a validated algorithm to detect treated recurrence in Medicare claims. Demographic and clinical characteristics collected at cancer diagnosis were assessed as predictors of late treated recurrence using restricted …

Prevalence Of Adverse Events Following T-Cell Redirecting Therapies In Patients With Metastatic Castration-Resistant Prostate Cancer: A Pooled Analysis, Abhiraj Saxena, Marc Yorker, Nicholas Zorko, Vivek Narayan, Bilal Siddiqui, Biren Saraiya, William Tester, Patrick Mille, Amy Shaver, Nikita Nikita, Grace Lu-Yao, W. Kevin Kelly, Kevin K. Zarrabi

Department of Medical Oncology Faculty Papers

BACKGROUND: T-cell redirecting therapies, including T-cell engagers (TCEs) and Chimeric Antigen Receptor T-cell (CAR-T), are under investigation in metastatic castration-resistant prostate cancer (mCRPC). Despite their promising therapeutic potential, these therapies remain in early stages of development due to treatment-related adverse events (TRAEs). This study aims to quantify the frequency and severity of adverse events in clinical trials with a pooled analysis.

MATERIALS AND METHODS: A systematic search of PubMed, CINHAL, Scopus, and Ovid was conducted to identify clinical trials evaluating TCEs or CAR-T in patients with mCRPC. Types and frequencies of TRAEs were collected and analyzed using a random-effects model. …

Social Prescribing For Refugee Populations: A Rapid Realist Review Of International Evidence, Victoria Touzel, Doreen Reifegerste, Luisa Bartz, Anna-Lena Esser, Kerryn Husk

Peninsula Medical School

BackgroundSocial prescribing offers potential for addressing social determinants of health and supporting health equity among disadvantaged groups. However, evidence for refugee populations remains limited, despite this group facing profound social and systemic barriers. This rapid realist review synthesizes social prescribing and comparable social-capital based intervention evidence to address this gap.MethodsWe conducted a RAMESES-compliant rapid realist review supported by an expert advisory board. Searches across six databases (2014–2024) were supplemented by grey literature and citation chasing strategies. Eligible studies included refugee, asylum-seekers and forcibly displaced populations engaged in either formal social prescribing or comparably operationalized social-capital interventions. Synthesis developed Context-Mechanism-Outcome configurations …

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Sarah Linnstaedt, Thomas Neylan, Lauren Mckibben, Liz Marie Albertorio-Sáez, Ying Zhao, Stacey House, Francesca Beaudoin, Xinming An, Jennifer Stevens, Gari Clifford, Tanja Jovanovic, Laura Germine, Scott Rauch, John Haran, Alan Storrow, Paul Musey, Phyllis Hendry, Sophia Sheikh, Brittany Punches, Robert Swor, Jose Pascual, Mark Seamon, Elizabeth M Datner, Claire Pearson, David Peak, Roland Merchant, Robert Domeier, Niels Rathlev, Brian O'Neil, Paulina Sergot, Leon Sanchez, Steven Bruce, Steven Harte, Ronald Kessler, Karestan Koenen, Kerry Ressler, Samuel Mclean, Aoife O'Donovan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

Nudging Implementation Of Low Tidal Volume Ventilation: A Stepped Wedge, Cluster Randomized Trial, Meeta Prasad Kerlin, Michael O. Harhay, Fan Li, Dylan S. Small, Yingying Lu, Wei Wang, Barry D. Fuchs, Mark E. Mikkelsen, Teresa Tran, Aerielle Belk, Jasmine A. Silvestri, Tamar Klaiman, Stefania Scott, Elizabeth Levy, Michael W. Sjoding, Rachel Kohn, Karsten J. Roberts, Rinad S. Beidas, Scott D. Halpern

College of Health Professions Faculty Papers

BACKGROUND: "Nudges" embedded in the electronic health record (EHR) facilitate desired decisions while preserving autonomy and may provide a scalable strategy to overcome the common implementation barrier of lack of knowledge about a best practice. We sought to test whether EHR-based nudges targeting two intensive care unit (ICU) clinician groups would safely increase evidence-based use of low tidal volume ventilation.

METHODS: We performed a stepped-wedge, cluster randomized, hybrid type 3 effectiveness-implementation trial in 12 ICUs from February 2021 to May 2023 to test three nudges targeting clinicians responsible for order entry and respiratory therapists responsible for operationalizing orders and documentation. …

Systemic Α₂-Agonist Use And Lower Hazard Of Glaucoma Compared With Β-Blockers: A Cohort Study, Ibrahim Abboud, Amin Z. Khudari, Abdelaziz Abdelaal, Amr Almobayed, Subhi J. Al'aref, Jonathan S. Myers, Richard K. Lee, Abdelrahman M. Elhusseiny

Wills Eye Hospital Papers

OBJECTIVE: Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

METHODS AND ANALYSIS: We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) …

Machine Learning-Based Prediction Of Proximal Junctional Pathology After Adult Spinal Deformity Surgery: A Systematic Review And Diagnostic Test Accuracy Meta-Analysis, Shaan Patel, Shiva A. Nischal, Yi Hein Chai, Kush M. Kale, Kevin Hines, Joshua Pelta-Heller, Jack Jallo, James S. Harrop, Srinivas K. Prasad

Department of Neurosurgery Faculty Papers

BACKGROUND: Proximal junctional kyphosis (PJK) and failure (PJF) remain challenging and incompletely predictable adverse event following adult spinal deformity (ASD) surgery. Machine learning (ML) models have been proposed to improve risk stratification, but performance varies and clinical applicability remains uncertain. A systematic review and diagnostic test accuracy meta-analysis was performed to synthesize the predictive performance of ML-based models for proximal junctional pathology after ASD surgery.

METHODS: PubMed, Embase, and CENTRAL were searched from inception to February 2026. Studies developing or validating ML models predicting PJK or PJF following ASD surgery were included. Diagnostic performance was synthesized using random-effects models, pooling …

Pharmacogenomic-Guided Prescribing And Polypharmacy Across Age Groups In Obsessive-Compulsive Disorder: A Retrospective Study, Sheldon R Garrison, Matthew W Boyer, Anthony W Zoghbi, Rachel A Schwartz, Nicolette Weisensel, Martin E Franklin, Madeline M Hartig, Maharaj Singh, Sreya Vadapalli

Faculty, Staff and Students Publications

Background: This study evaluated medication utilization in children, adolescents, and adults with obsessive-compulsive disorder (OCD), a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors. Although first-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), the heterogeneous biological underpinnings contribute to suboptimal outcomes, with 40-60% of individuals not responding to SSRIs. This complex phenotype often leads to psychotropic polypharmacy, which may be mitigated by incorporating combinatorial pharmacogenomic (PGx) testing into protocol-based care to identify potential gene-drug interactions.

Methods: A retrospective review was conducted of individuals with OCD aged 8 to 65 years who received either …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

Cd8+ T Cell Differentiation Into Nk-Like Effector Cells Drives Transplant Rejection, Dawei Zou, Stephanie G Yi, Yulin Dai, Luan Truong, Lillian W Gaber, Richard J Knight, Xiang Xiao, Rafik M Ghobrial, Xian C Li, Zhongming Zhao, Wenhao Chen, A Osama Gaber

Faculty, Staff and Student Publications

T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8+ T cell subset exhibiting killer cell lectin-like receptor (KLR)+ NK-like features. Mechanistic studies in mice showed that the KLR+ subset emerged de novo post-transplantation and dominated the CD8+ T cell infiltrate in rejecting allografts. These NK-like CD8+ T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the …

Characterizing Core Outcomes Of Responsible Stewardship For Human Genomic Data In The Cloud, Vasiliki Rahimzadeh, Bronwyn Walsh, Heidi L Rehm, Mildred Cho, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

We present findings from a scoping review of the genomic data sharing literature used to inform a core outcomes set for responsible data stewardship in the cloud. Genomic and related health data stemming from government funded research have undergone mass migration to the cloud where they can be more securely stored, accessed, and analyzed within shared computing environments. While this migration reflects a shift in privacy and security infrastructure for cloud-based repositories as oversight becomes more globalized, it also necessitates new data stewardship responsibilities to align authorized data access with ethical data use. Responsible data stewardship refers to the ethical …

Large-Scale Genetic Characterization Of Parkinson’S Disease In The African And African Admixed Populations, Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Kathryn Step, Emily Waldo, Mathew J Koretsky, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Suleyman Can Akerman, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Christiane Alvarez, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francesca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Purine Metabolic Adaptation Protects The Endothelium From Disturbed Flow-Induced Dna Damage And Atherosclerosis, Qian Ma, Yongfeng Cai, Zhidan Zhang, Dingwei Zhao, Yuan Zhao, Peishan Xu, Tammy Lu, Wendy Zhang, Qiuhua Yang, Yaqi Zhou, Varadarajan Sudhahar, Tohru Fukai, Hanjoong Jo, Yiming Xu, Yuqing Huo

Faculty, Staff and Students Publications

Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions develop preferentially at arterial regions exposed to disturbed flow (d-flow), which induces genomic stress, endothelial injury, and barrier dysfunction. Hemodynamic forces are known to reprogram endothelial metabolism, but the role of de novo purine synthesis (DNPS), which supplies nucleotides for genome maintenance and whose terminal steps are catalyzed by the bifunctional enzyme ATIC, remains undefined in atherosclerosis. By integrating bulk and single-cell multiomics with in vitro flow systems and in vivo models, we show that d-flow upregulates DNPS and ATIC …

Apathy, Effort-Based Decisions And Brain Integrity In Alzheimer’S And Parkinson’S Diseases, Lee-Anne Morris, Hideo Suzuki, Seonjoo Lee, Zekai Jin, Bryan B Chen, Ana Marin, Edward D Huey, Yunglin Gazes, Sarah R Heilbronner, Campbell J Le Heron, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy, or loss of motivation, is a prominent syndrome accompanying both Alzheimer's and Parkinson's diseases, in addition to other disorders. One approach to understanding motivational loss is to examine the processes underlying goal-directed behaviour. Weighing up rewarding outcomes against the effort costs required to obtain them (effort-based decision-making) is a core computation when deciding to act for outcomes. Although a growing body of evidence points to disruption of this computation in people with apathy, which underlying decision parameters drive this disruption, their neural associations and whether these would generalize or differ across brain disorders have not been examined. People with …

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

Faculty, Staff and Student Publications

Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Tractor Workflow: A Scalable Nextflow Framework For Local Ancestry-Aware Genome-Wide Association Studies, Nirav N Shah, Taotao Tan, Jessica Honorato-Mauer, Yi-Sian Lin, Adam X Maihofer, Clement C Zai, Pgc-Ptsd Ancestry Working Group, Marcos Santoro, Caroline M Nievergelt, Elizabeth G Atkinson

Faculty, Staff and Students Publications

Motivation: The routine exclusion of admixed individuals from traditional genome-wide association studies (GWAS) due to concerns about spurious associations has limited multi-ancestry genetic discovery. Tractor addresses this issue by incorporating local ancestry into association testing, enabling the identification of ancestry-enriched signals and generating ancestry-specific summary statistics. However, adoption has been constrained by the complexity of prerequisite steps, including phasing and local ancestry inference, which require substantial bioinformatics expertise and introduce key analytical decision points.

Results: We developed a scalable, automated Nextflow workflow that integrates phasing, local ancestry inference, and Tractor association testing into a reproducible end-to-end pipeline. To demonstrate its …

Metabolic Dysfunction And Metabolic Management In Episodic Migraine, Delora E. Denney, Michael J. Marmura

Department of Jefferson Headache Center Papers and Presentations

PURPOSE OF REVIEW: Evidence suggests a significant link between migraine and metabolic syndrome,, especially in those with chronic or refractory migraine. Weight loss and exercise may effectively prevent migraine. Here, we review the evidence behind exercise and weight loss as migraine treatments.

RECENT FINDINGS: While metabolic syndrome and pain have long had a known association, only recently have strong studies demonstrated a higher risk of developing metabolic syndrome in people with migraine. Additionally, other sequelae of metabolic syndrome, obesity, hypertension, hypercoagulability, and diabetes also interplay with migraine. New medications like GLP-1 agonists may be a potential treatment for migraine as …

Experiences Of Discrimination, Paternal Support, And Hypertensive Disorders Of Pregnancy (Hdp) In The Miehr Study, Houston, Texas, Tahereh Alinia, Elaine Symanski, Juan Manuel Alvarez, Kristina Walker Whitworth

Faculty, Staff and Students Publications

Background: Discrimination is a psychosocial stressor that, through activation of stress-response pathways, may influence risk of adverse perinatal health outcomes. However, few studies have evaluated the association between discrimination and hypertensive disorders of pregnancy (HDP), and none have explored effect modification by race or paternal support, which may buffer the adverse effects of discrimination.

Methods: We included 1,847 non-Hispanic Black and White participants from the Maternal and Infant Environmental Health Riskscape (MIEHR) study. Krieger's validated Experiences of Discrimination (EOD) scale was used to assess occurrence (yes/no) and frequency (once, 2-3, ≥ 4 times) of discrimination in nine situations. We created …

Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock, Kelly E Sanders, Marissa D Pokharel, Baron K Osborn, Yao-Wei Wang, Charles E Wade, Lucy Z Kornblith, Mitchell J Cohen, Jessica C Cardenas

Faculty, Staff and Student Publications

Background: Hemorrhagic shock (HS) following traumatic injury is hallmarked by innate immune activation, hypercoagulability, and thromboinflammatory complications. To date, the direct link between HS, injury severity, and endothelial cell (EC) contributions to thromboinflammation remains poorly understood. The goals of this study were to determine the impact of injury severity and HS on endothelial-mediated thromboinflammation and examine whether these changes increase the propensity for thrombosis.

Methods: Plasma from 89 male trauma patients, stratified by HS and injury severity, and 10 healthy subjects were assessed for inflammatory mediators by BioPlex. Human lung microvascular endothelial cells were exposed to patient plasma for 4 …

Clinical And Demographic Characteristics Of Hospitalized Patients With Xylazine-Related Wounds, Elizabeth Novick, Nikhil Seval, Dagan Coppock, Mollie Tucker, Daniel Taupin, John Zurlo, Carolyn Kramer

Department of Medicine Faculty Papers

OBJECTIVES: Little is known about the demographic and clinical features of patients with xylazine-related wounds. We sought to characterize hospitalized patients with substance use disorder (SUD) and xylazine-related wounds seen for infectious diseases consultation.

METHODS: We retrospectively reviewed the medical records of 193 patients diagnosed with SUD at 3 Philadelphia hospitals between October 2023 and January 2024. Patients were identified as either being diagnosed with (n=73) or without (n=120) xylazine-related wounds. We compared the demographic and clinical features between the 2 groups.

RESULTS: Patients diagnosed with wounds were younger ( P < 0.001), more likely to be White or Hispanic and less likely to be Black/AA ( P < 0.001), more likely to have tested positive for fentanyl ( P < 0.001), amphetamines ( P < 0.001), and cocaine ( P 0.001), more likely to acknowledge injection ( P < 0.001), and more likely to leave the hospital by patient-directed discharge (PDD) ( P < 0.001). Most patients had multiple wounds (75%), and more than half (53%) had at least one wound greater than 10 cm at its widest dimension. Although most patients diagnosed with wounds received antibiotics, many did not have symptoms or signs of infection.

CONCLUSIONS: Xylazine-related wounds are highly associated with illicitly manufactured …

Leading With Hope: A Clinical Communication Campaign To Promote Partner Hiv Testing In Assisted Partner Notification And Antenatal Care Programs In Uganda., Emily A. Hurley, Violet Gwokyala, Linda Kisaakye Nabitaka, Jolly Beyeza Kashesya, Mercylynn Agasha, Florence Namaganda, Nikolaus Schuetz, J Nalubega Ross, Joseph K B Matovu, Rhoda Wanyenze, Glenn Wagner, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

Among heterosexual couples in sub-Saharan Africa, fears of relationship dissolution and inability to bear healthy children following an HIV-positive result remain barriers to HIV testing. Recently expanded availability of pre-exposure prophylaxis (PrEP) affords a critical opportunity to promote HIV testing with reassuring communication that highlights use for relationship preservation and healthy childbearing. We aimed to develop a theoretically-grounded communication intervention to promote partner HIV testing within assisted partner notification (APN) and antenatal care (ANC) programs in Uganda. Through an 18-month iterative co-creation process, we developed the HOPE Clinical Communication Campaign (HOPE-CCC) in collaboration with a project advisory board (PAB) of …

Exploring The Alignment Between Medical School Outcomes With Residency Competencies: A Modified Delphi Study, Sally A. Santen, Luan Lawson, Jose A. Negrete Manriquez, Marjorie Westerveld, Laurah Turner, Anita Wilson, Phd, Yoon Soo Park, Eric S. Holmboe, Michael S. Ryan, Medical School Outcomes Milestone Study Group

JeffMD Academic Affairs

PURPOSE: Facilitation of competency-based medical education adoption would benefit from alignment between medical school (undergraduate medical education [UME]) and residency (graduate medical education [GME]) assessments. This study explores the strength of an a priori alignment of medical school assessments with residency competency domains to guide programmatic assessment and research.

METHOD: In fall 2023, the authors (US faculty with UME and GME expertise) used a 2-phase Delphi consensus approach (9 participants in phase 1 and 16 in phase 2) to independently map medical school assessments to the Accreditation Council for Graduate Medical Education competency domains (0, no association; 1, some or …

Domain-Specific Concussion Knowledge And Reporting In United States Major League Rugby Players, Julie Stamm, Katherine Hunzinger, Owen Sheehy, Christine Baugh

Department of Exercise Science Faculty Papers

Previous research indicates high concussion knowledge is not associated with better concussion reporting, with research examining the relationship between reporting and global concussion knowledge. Concussion knowledge has not yet been investigated in United States Major League Rugby (MLR) players. This study evaluated domain-specific concussion knowledge, concussion history, and reporting behaviors among active MLR players. In a cross-sectional design, 207 MLR athletes (age 26.6 ± 3.4 years) completed a survey assessing concussion history, knowledge, and nondisclosure reasons. While in the MLR, 24% reported an undisclosed concussion, with nondisclosure reasons related to a lack of concussion knowledge, a desire to continue playing, …

Eptinezumab In Treatment-Resistant Chronic Migraine: Four-Year Real-World Effectiveness And Treatment Persistence, Wan-Jen Hsieh, Kelly Nicol, Chai Ching Ng, Tsung-Wei Hou, Phillip Phan, Scott W. Keith, Brittany Heckel, Michael J. Marmura, Hsiangkuo Yuan

Department of Neurology Faculty Papers

AimTo evaluate 48-month real-world outcomes of eptinezumab users in chronic migraine (CM), including longitudinal effectiveness, treatment persistence, reasons for discontinuation, and post-discontinuation anti-calcitonin gene-related peptide (CGRP) treatment patterns.MethodsWe conducted a retrospective cohort study of 112 CM subjects initiating eptinezumab at a tertiary headache center between 2019 and 2021. Monthly headache days (MHD), migraine disability assessment (MIDAS), and average pain intensity (API) were extracted at baseline and every 6 months for up to 48 months using a predefined outcome form at each visit. Longitudinal changes were analyzed using generalized estimating equations (GEE) with an unstructured correlation matrix, adjusting for age, sex, …

Population Pharmacokinetics And Dosing Simulations Of Pentobarbital In The Pediatric Population, Victoria Etges Helfer, Lorena Medina-Aymerich, William J. Muller, Marisa Meyer, Amira Al-Uzri, Russell Mcculloh, Chi D. Hornik, Stephen J. Balevic, Rachel G. Greenberg, Daniel K. Benjamin, Sarah G. Anderson, Daniel Gonzalez

Department of Pediatrics Faculty Papers

Pentobarbital is a barbiturate with sedative and anticonvulsant properties, occasionally used in pediatric patients for preoperative sedation, deep sedation during mechanical ventilation, and seizure control. Despite its long-standing clinical use, age-appropriate dosing remains challenging due to variability across studies and limited pediatric pharmacokinetic (PK) data. This study (NCT01431326) aimed to characterize the population pharmacokinetics of pentobarbital in pediatric patients (birth to 21 years) and evaluate dosing strategies using model-based simulations. A two-compartment population PK model, allometrically scaled to total body weight, adequately described pentobarbital plasma concentrations, with no additional covariates identified as significant. Simulations were conducted across four age groups: …

Diacylglycerol Kinase Eta As A Novel Target In Nras Mutant Melanoma, Haley P. Wilson, Casey D. Stefanski, Signe Caksa, Glenn L. Mersky, Scott D. Varney, Jelan I. Haj, Dan A. Erkes, Timothy J. Purwin, Vivian Chua, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

NRAS mutations occur in 10%-30% of cutaneous melanomas and are associated with high tumor mutational burden. Mutant NRAS signaling drives aberrant cell growth and proliferation, in part, through activation of the RAF-MEK-ERK1/2 kinase pathway; however, targeted therapies to this pathway have limited effectiveness in patients with NRAS mutant melanoma. The role of other targetable signaling pathways in NRAS mutant melanoma is poorly characterized. Here, we demonstrated that one isoform of diacylglycerol kinase, diacylglycerol kinase eta (DGKη), a lipid signaling regulator, was highly expressed in NRAS mutant melanoma patient samples. Knockdown of DGKH in NRAS mutant melanoma cell lines resulted in …

Screening For Hypertension And Diabetes In Laundromats In The Largest Hispanic-Majority City In The U.S, Nicholas A Mccann, Vanessa Schick, Jack Tsai

Faculty, Staff and Student Publications

Purpose: This study aimed to assess the prevalence of hypertension and diabetes among laundromat users in San Antonio, Texas, and explore laundromats as a novel setting for health interventions regarding these 2 conditions.

Design: This descriptive, cross-sectional study involved demographic, blood pressure and HbA1c screenings to assess the health status of laundromat users.

Setting: The study took place in 7 laundromats in low-income areas of San Antonio.

Subjects: A total of 150 adults aged 18 and older who regularly used the laundromats and spoke either English or Spanish were eligible to participate.

>Measures: Hypertension was defined as a systolic BP …