Medicine and Health Sciences Commons^™

Whole Genome Sequencing Based Analysis Of Inflammation Biomarkers In The Trans-Omics For Precision Medicine (Topmed) Consortium, Min-Zhi Jiang, Sheila M Gaynor, Xihao Li, Eric Van Buren, Adrienne Stilp, Erin Buth, Fei Fei Wang, Regina Manansala, Stephanie M Gogarten, Zilin Li, Linda M Polfus, Shabnam Salimi, Joshua C Bis, Nathan Pankratz, Lisa R Yanek, Peter Durda, Russell P Tracy, Stephen S Rich, Jerome I Rotter, Braxton D Mitchell, Joshua P Lewis, Bruce M Psaty, Katherine A Pratte, Edwin K Silverman, Robert C Kaplan, Christy Avery, Kari E North, Rasika A Mathias, Nauder Faraday, Honghuang Lin, Biqi Wang, April P Carson, Arnita F Norwood, Richard A Gibbs, Charles Kooperberg, Jessica Lundin, Ulrike Peters, Josée Dupuis, Lifang Hou, Myriam Fornage, Emelia J Benjamin, Alexander P Reiner, Russell P Bowler, Xihong Lin, Paul L Auer, Laura M Raffield, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Inflammation Working Group

Faculty, Staff and Student Publications

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant …

Diagnostic Utility Of Dna Methylation Analysis In Genetically Unsolved Pediatric Epilepsies And Chd2 Episignature Refinement, Christy W Laflamme, Cassandra Rastin, Soham Sengupta, Helen E Pennington, Sophie J Russ-Hall, Amy L Schneider, Emily S Bonkowski, Edith P Almanza Fuerte, Talia J Allan, Miranda Perez-Galey Zalusky, Joy Goffena, Sophia B Gibson, Denis M Nyaga, Nico Lieffering, Malavika Hebbar, Emily V Walker, Daniel Darnell, Scott R Olsen, Pandurang Kolekar, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Haley Mcconkey, Jennifer Kerkhof, Michael A Levy, Raissa Relator, Dorit Lev, Tally Lerman-Sagie, Kristen L Park, Marielle Alders, Gerarda Cappuccio, Nicolas Chatron, Leigh Demain, David Genevieve, Gaetan Lesca, Tony Roscioli, Damien Sanlaville, Matthew L Tedder, Sachin Gupta, Elizabeth A Jones, Monika Weisz-Hubshman, Shamika Ketkar, Hongzheng Dai, Kim C Worley, Jill A Rosenfeld, Hsiao-Tuan Chao, Undiagnosed Diseases Network, Geoffrey Neale, Gemma L Carvill, University Of Washington Center For Rare Disease Research, Zhaoming Wang, Samuel F Berkovic, Lynette G Sadleir, Danny E Miller, Ingrid E Scheffer, Bekim Sadikovic, Heather C Mefford

Faculty, Staff and Students Publications

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also …

Epigenetic Associations With Neonatal Age In Infants Born Very Preterm, Particularly Among Genes Involved In Neurodevelopment., Kenyaita M. Hodge, Amber A. Burt, Marie Camerota, Brian S. Carter, Jennifer Check, Karen N. Conneely, Jennifer Helderman, Julie A. Hofheimer, Anke Hüls, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Sheri A. Dellagrotta, Lynne M. Dansereau, T Michael O'Shea, Carmen J. Marsit, Barry M. Lester, Todd M. Everson

Manuscripts, Articles, Book Chapters and Other Papers

The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.

Benefits And Challenges Of Geographic Information Systems (Gis) For Data-Driven Outreach In Black Communities Experiencing Overdose Disparities: Results Of A Stakeholder Focus Group, Devin E Banks, Maria Paschke, Rashmi Ghonasgi, Vetta L Sanders Thompson

2020-Current year OA Pubs

BACKGROUND: Black individuals in the U.S. face increasing racial disparities in drug overdose related to social determinants of health, including place-based features. Mobile outreach efforts work to mitigate social determinants by servicing geographic areas with low drug treatment and overdose prevention access but are often limited by convenience-based targets. Geographic information systems (GIS) are often used to characterize and visualize the overdose crisis and could be translated to community to guide mobile outreach services. The current study examines the initial acceptability and appropriateness of GIS to facilitate data-driven outreach for reducing overdose inequities facing Black individuals.

METHODS: We convened a …

Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh

Faculty, Staff and Student Publications

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire.

METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group.

RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by …

Brca1 Secondary Splice-Site Mutations Drive Exon-Skipping And Parp Inhibitor Resistance, Ksenija Nesic, John J Krais, Et Al.

2020-Current year OA Pubs

PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame. BRCA1 splice isoforms △11 and △11q can contribute to PARPi resistance by splicing out the mutation-containing exon, producing truncated, partially functional proteins. However, the clinical impacts and underlying drivers of BRCA1 exon skipping are not fully understood.We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift …

Adjuvant External Beam Radiotherapy Combined With Brachytherapy For Intermediate-Risk Cervical Cancer, Nuria Agusti, David Viveros-Carreño, Alexander Melamed, Rene Pareja, Alexa Kanbergs, Chi-Fang Wu, Roni Nitecki, Lauren Colbert, Jose Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer.

Methods: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 …

Women In Stem Becoming Independent: Our Shared Motivation And Enthusiasm Are Our Driving Force, Liudmila Andreeva, Lidia Bosurgi, Shu Zhen Chong, Coco Chu, Yejing Ge, Esther Hoste, Kellie A Jurado, Jette Lengefeld, Archita Mishra, Stefanie Wculek, Arabella Young

Faculty, Staff and Student Publications

This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.

Phase Ii Study Of Vemurafenib In Children And Young Adults With Tumors Harboring Braf V600 Mutations: Nci-Cog Pediatric Match Trial (Apec1621) Arm G, Marie V Nelson, Aerang Kim, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent D Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Nilsa C Ramirez, Alok Jaju, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Center for Medical Ethics and Health Policy Staff Publications

Background: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations.

Methods: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib.

Results: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to …

Maturation Of Germinal Center B Cells After Influenza Virus Vaccination In Humans, Katherine M Mcintire, Wooseob Kim, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Jackson S Turner, Ali H. Ellebedy, Et Al.

2020-Current year OA Pubs

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity …

Tumour-Intrinsic Endomembrane Trafficking By Arf6 Shapes An Immunosuppressive Microenvironment That Drives Melanomagenesis And Response To Checkpoint Blockade Therapy, Yinshen Wee, Junhua Wang, Emily C Wilson, Coulson P Rich, Aaron Rogers, Zongzhong Tong, Evelyn Degroot, Y N Vashisht Gopal, Michael A Davies, H Atakan Ekiz, Joshua K H Tay, Chris Stubben, Kenneth M Boucher, Juan M Oviedo, Keke C Fairfax, Matthew A Williams, Sheri L Holmen, Roger K Wolff, Allie H Grossmann

Faculty, Staff and Student Publications

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with …

Characterization Of Turbo, A Tlr Ligand-Based Adjuvant For Glycoconjugate Vaccines, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Many bacterial polysaccharide vaccines, including the typhoid Vi polysaccharide (ViPS) and tetravalent meningococcal polysaccharide conjugate (MCV4) vaccines, do not incorporate adjuvants and are not highly immunogenic, particularly in infants. I found that endotoxin, a TLR4 ligand in ViPS, contributes to the immunogenicity of typhoid vaccines. Because endotoxin is pyrogenic, and its levels are highly variable in vaccines, I developed monophosphoryl lipid A, a nontoxic TLR4 ligand-based adjuvant named Turbo. Admixing Turbo with ViPS and MCV4 vaccines improved their immunogenicity across all ages and eliminated booster requirement. To understand the characteristics of this adjuvanticity, I compared Turbo with alum. Unlike alum, …

Dihydrothiazolo Ring-Fused 2-Pyridone Antimicrobial Compounds Streptococcus Pyogenes Skin And Soft Tissue Infection, Zongsen Zou, Pardeep Singh, Jerome S Pinkner, Chloe L P Obernuefemann, Wei Xu, Taylor M Nye, Karen W Dodson, Fredrik Almqvist, Scott J Hultgren, Michael G Caparon

2020-Current year OA Pubs

We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that has antimicrobial activities against a broad spectrum of Gram-positive pathogens. Here, we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by

Population-Level Trends In Self-Reported Healthcare Utilization Among Older Adults In Mexico With And Without Cognitive Impairment, José Eduardo Cabrero Castro, Rebeca Wong, Rafael Samper Ternent, Brian Downer

Faculty, Staff and Student Publications

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico.

METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and …

Brca1-Mediated Dual Regulation Of Ferroptosis Exposes A Vulnerability To Gpx4 And Parp Co-Inhibition In Brca1-Deficient Cancers, Guang Lei, Chao Mao, Amber D Horbath, Yuelong Yan, Shirong Cai, Jun Yao, Yan Jiang, Mingchuang Sun, Xiaoguang Liu, Jun Cheng, Zhihao Xu, Hyemin Lee, Qidong Li, Zhengze Lu, Li Zhuang, Mei-Kuang Chen, Anagha Alapati, Timothy A Yap, Mien-Chie Hung, Mingjian James You, Helen Piwnica-Worms, Boyi Gan

Faculty, Staff and Student Publications

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i …

Rosiglitazone And Trametinib Exhibit Potent Anti-Tumor Activity In A Mouse Model Of Muscle Invasive Bladder Cancer, Sakina A Plumber, Tiffany Tate, Hikmat Al-Ahmadie, Xiao Chen, Woonyoung Choi, Merve Basar, Chao Lu, Aaron Viny, Ekatherina Batourina, Jiaqi Li, Kristjan Gretarsson, Besmira Alija, Andrei Molotkov, Gregory Wiessner, Byron Hing Lung Lee, James Mckiernan, David J Mcconkey, Colin Dinney, Bogdan Czerniak, Cathy Lee Mendelsohn

Faculty, Staff and Student Publications

Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

Gastrocnemius Electrical Stimulation Increases Ankle Dorsiflexion Strength In Patients With Post-Acute Sequelae Of Sars-Cov-2 (Pasc): A Double-Blind Randomized Controlled Trial, Myeounggon Lee, Alejandro Zulbaran-Rojas, Miguel Bargas-Ochoa, Bernardo Martinez-Leal, Rasha Bara, Areli Flores-Camargo, M G Finco, Ram Kinker Mishra, Jaewon Beom, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

Post-Acute sequelae of SARS-CoV-2 (PASC) is a multisystem disorder causing persistent musculoskeletal deconditioning and reduced lower extremity strength. Electrical stimulation (E-Stim) to the gastrocnemius muscle can enhance strength outcomes by increasing the frequency of muscle fiber activation. We investigated its effect on individuals with PASC. Participants were randomized into intervention (IG) or control (CG) groups. The IG self-administered daily one-hour E-Stim to both their gastrocnemius muscles using a functional device over 4-week, while the CG used a sham device. Primary outcomes were ankle dorsiflexion strength assessed via dynamometry during maximum voluntary contractions, and gastrocnemius voluntary activation (GVA) via surface electromyography. …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E. Quiring, Raeann M. Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H. Parikh, Benjamin A. Fink, Thomas Mueller, Gordon Brown

Jefferson Health - New Jersey Papers

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

Utilizing The 4ms Framework To Create A Structure And Process To Support Voluntary Health Assessments In Affordable Housing, Elyse Perweiler, Jennifer Degennaro, Sherry Pomerantz, Marilyn Mock, Margaret Avallone, Aaron Truchil, Stephen Singer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: A growing number of older adults live in senior affordable housing, many with limited support systems and representing underserved or disadvantaged populations. Staff in these buildings are in a unique position to identify and address the healthcare and biopsychosocial needs of their residents and link them to services and supports.

METHODS: Staff in four affordable housing sites received training on the 4Ms approach to caring for older adults and conducting resident health assessments. They learned to collect comprehensive health information using a 4Ms Resident Health Risk Assessment (4Ms-RHRA) and results are entered into a customized electronic database. Embedded flags …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E Quiring, Raeann M Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H Parikh, Benjamin A Fink, Thomas Mueller, Gordon Brown

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

Best Quality Vs. Sex Selection - An Analysis Of Embryo Selection Preferences For Patients Undergoing Preimplantation Genetic Testing For Aneuploidy Over A 10-Year Period, Pavan Gill, Christine Whitehead, Marie Werner, Emre Seli

Jefferson Health - New Jersey Papers

PURPOSE: Investigate patient preferences in embryo selection for transfer regarding quality versus sex in IVF/ICSI cycles with PGT-A and assess associated clinical implications.

METHODS: Retrospective cohort study at a university fertility practice from January 2012 to December 2021. Included were patients undergoing single frozen euploid transfers with at least one embryo of each sex available. Primary outcomes were preference for embryo selection (quality vs. sex) and sex preference (male vs. female). Trends over 10 years were evaluated and clinical outcomes, including clinical pregnancy rate (CPR), sustained implantation rate (SIR), and live birth rate (LBR), were compared.

RESULTS: A total of …

High-Grade Liver Injuries With Contrast Extravasation Managed Initially With Interventional Radiology Versus Observation: A Secondary Analysis Of A Wta Multicenter Study, Negaar Aryan, Areg Grigorian, Erika Tay-Lasso, Michael Cripps, Heather Carmichael, Robert Mcintyre, Shane Urban, Catherine Velopulos, Clay Cothren Burlew, Shana Ballow, Rachel C. Dirks, Aimee Lariccia, Michael S. Farrell, Deborah M. Stein, Michael S. Truitt, Heather M. Grossman Verner, Caleb J. Mentzer, T. J. Mack, Chad G. Ball, Kaushik Mukherjee, Georgi Mladenov, Daniel J. Haase, Hossam Abdou, Thomas J. Schroeppel, Jennifer Rodriquez, Miklosh Bala, Natasha Keric, Morgan Crigger, Navpreet K. Dhillon, Eric J. Ley, Tanya Egodage, John Williamson, Tatiana Cp Cardenas, Vadine Eugene, Kumash Patel, Kristen Costello, Stephanie Bonne, Fatima S. Elgammal, Warren Dorlac, Claire Pederson, Nicole L. Werner, James M. Haan, Kelly Lightwine, Gregory Semon, Kristen Spoor, Laura A. Harmon, Jason M. Samuels, M. C. Spalding, Jeffry Nahmias

Department of Surgery Faculty Publications

Background: High-grade liver injuries with extravasation (HGLI + Extrav) are associated with morbidity/mortality. For low-grade injuries, an observation (OBS) first-strategy is beneficial over initial angiography (IR), however, it is unclear if OBS is safe for HGLI + Extrav. Therefore, we evaluated the management of HGLI + Extrav patients, hypothesizing IR patients will have decreased rates of operation and mortality. Methods: HGLI + Extrav patients managed with initial OBS or IR were included. The primary outcome was need for operation. Secondary outcomes included liver-related complications (LRCs) and mortality. Results: From 59 patients, 23 (39.0%) were managed with OBS and 36 (61.0%) …

Safety And Feasibility Of Third-Party Cytotoxic T Lymphocytes For High-Risk Patients With Covid-19, Dolores Grosso, John L. Wagner, Allyson O'Connor, Kaitlyn Keck, Yanping Huang, Zi-Xuan Wang, Hilary Mehler, Benjamin Leiby, Phyllis Flomenberg, Usama Gergis, Neda Nikbakht, Michael Morris, Julie Karp, Alexis R. Peedin, Neal Flomenberg

COVID-19 Papers, Posters, and Presentations

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received …

In-Hospital Risk Factors For Reintervention And Amputation In Brachial Arterial Trauma, Aast Proovit Study Group, Justin M. Robbins, Corinna Crayton, Isaac Koloditch, Casey Walk, Limayre Gramajo, Samantha Shugar, Peter Ekeh, Joseph Dubose, Yee Wong, Cathline Layba

Department of Surgery Faculty Publications

Introduction: Brachial artery trauma is a rare but potentially devastating injury. There is little data regarding risk factors for reintervention and amputation prevention in this population, as well as anticoagulant (AC) and antiplatelet (AP) regimens and outcomes after discharge in trauma patients with vascular injuries requiring repair. This study aims to identify in-hospital risk factors for reintervention and amputation and stratify outcomes of follow-up by discharge AC or AP regimen. Methods: The AAST Prospective Observational Vascular Injury Trial database was queried for all patients who underwent traumatic brachial arterial repair from 2013 to 2022. Patients were evaluated by need for …

Plasma Galectin-9 Relates To Cognitive Performance And Inflammation Among Adolescents With Vertically Acquired Hiv, Preeti Moar, Soe Mar, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored.

DESIGN: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n  = 15), ART-naive ( n  = 15), and adolescents without HIV (AWOH; n  = 10)] and Myanmar [AWH on ART ( n  = 54) and AWOH ( n  = 22)] were studied. …

Dual-Energy Lattice-Tip Ablation System For Persistent Atrial Fibrillation: A Randomized Trial., Elad Anter, Moussa Mansour, Devi G Nair, Dinesh Sharma, Tyler L Taigen, Petr Neuzil, Erich L Kiehl, Josef Kautzner, Jose Osorio, Stavros Mountantonakis, Andrea Natale, John D Hummel, Anish K Amin, Usman R Siddiqui, Doron Harlev, Paul Hultz, Shufeng Liu, Birce Onal, Khaldoun G Tarakji, Vivek Y Reddy

Heart and Vascular Articles

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year …

De-Escalation Of Disease-Modifying Therapy For People With Multiple Sclerosis Due To Safety Considerations: Characterizing 1-Year Outcomes In 25 People Who Switched From Ocrelizumab To Diroximel Fumarate., Mark Gudesblatt, Barbara Bumstead, Marijean Buhse, Myassar Zarif, Sarah A Morrow, Jacqueline A Nicholas, Laura M Hancock, Jeffrey Wilken, Joanna Weller, Nicole Scott, Anne Gocke, James B Lewin, Olivia Kaczmarek, Jason P Mendoza, Daniel Golan

Neuroscience Articles

INTRODUCTION: Switching disease-modifying therapy (DMT) may be considered for relapsing-remitting multiple sclerosis (RRMS) if a patient's current therapy is no longer optimal. This was particularly important during the recent COVID-19 pandemic because of considerations around immune deficiency and impaired vaccine response associated with B cell-depleting DMTs. This real-world, single-center study aimed to evaluate change or decline in functional ability and overall disease stability in people with RRMS who were switched from B cell-depleting ocrelizumab (OCRE) to diroximel fumarate (DRF) because of safety concern related to the COVID-19 pandemic.

METHODS: Adults with RRMS were included if they had been clinically stable …

Risk Factors For Malalignment After Intramedullary Nail Treatment Of Distal Tibia Fractures With Associated Fibula Fractures., Yash P Chaudhry, Jose M Gutierrez-Naranjo, Micheal Raad, Diane Ghanem, Luis M Salazar, Jason T Goodrum, Kitchai Luksameearunothai, Boris A Zelle, Erik A Hasenboehler

Orthopedic Surgery Resident Research

PURPOSE: Malalignment of distal tibia fractures can lead to malunion/nonunion or alter the limb mechanical axis which may cause arthritis. Proposed methods to decrease malalignment include fibular fixation or multiplanar interlocking screws, however these remain controversial. This study aimed to identify factors associated with malalignment in distal tibial fractures with associated fibular shaft fractures.

METHODS: A retrospective review was performed of distal tibia fractures with associated fibular shaft fractures treated with intramedullary nailing at two level one trauma centers between 2015 and 2019. Cases involving malalignment (> 5° of deviation from anatomic axis on either coronal/sagittal axis) on final follow-up …

Buprenorphine Prescribing Characteristics Following Relaxation Of X-Waiver Training Requirements., Paul J. Christine, Rouba A. Chahine, Simeon D. Kimmel, Nicole Mack, Christian Douglas, Thomas J. Stopka, Katherine Calver, Laura C. Fanucchi, Svetla Slavova, Michelle R. Lofwall, Daniel J. Feaster, Michael Lyons, Jerel M. Ezell, Marc R. Larochelle

Center on Drug and Alcohol Research Faculty Publications

IMPORTANCE: Local-level data are needed to understand whether the relaxation of X-waiver training requirements for prescribing buprenorphine in April 2021 translated to increased buprenorphine treatment.

OBJECTIVE: To assess whether relaxation of X-waiver training requirements was associated with changes in the number of clinicians waivered to and who prescribe buprenorphine for opioid use disorder and the number of patients receiving treatment.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study uses an interrupted time series analysis of 2020-2022 data from the HEALing Communities Study (HCS), a cluster-randomized, wait-list-controlled trial. Urban and rural communities in 4 states (Kentucky, Massachusetts, New York, and Ohio) …