Health Services Research Commons^™

Safety Of Carotid Endarterectomy In The Elderly And Octogenarian Population: A Nationwide Study Including 80,000 Patients, Victor Gabriel El-Hajj, Joanna Roy, Basel Musmar, Wi Jin Kim, Michael Rizzuto, Nathaniel Ellens, Rabab Alshahrani, Victor Staartjes, Adrian Elmi-Terander, Ramachandra Tummala, Stavropoula Tjoumakaris, Michael Gooch, Robert Rosenwasswer, Ziad Khabbaz, Pascal Jabbour

Department of Neurosurgery Faculty Papers

INTRODUCTION: Carotid endarterectomy (CEA) is an established procedure for stroke prevention in patients with carotid artery stenosis. While CEA is considered safe in younger patients, perioperative risks in octogenarians remain debated, with current guidelines classifying the procedure as "high-risk" in this patient population. This study aimed to evaluate short-term outcomes of CEA across age groups and to assess whether comorbidity burden better predicts outcomes than chronological age.

METHODS: The ACS-NSQIP database (2013-2020), was used to identify patients eligible for inclusion. The cohort was stratified based on age <  60, 60-80, and > 80 years. Propensity score matching and multivariable logistic regression were used to compare …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Music Therapy Versus Cognitive Behavioral Therapy Via Telehealth For Anxiety In Survivors Of Cancer: A Randomized Clinical Trial, Kevin T. Liou, Joke Bradt, M. Beatriz Currier, Raymond Baser, Katherine Panageas, Jodi Macleod, Desiree Walker, Susan Q. Li, Ana Maria Lopez, Kelly Mcconnell, Jun J. Mao

Department of Medical Oncology Faculty Papers

PURPOSE: Anxiety is prevalent, disruptive, and undertreated among survivors of cancer. Cognitive behavioral therapy (CBT) is the first-line treatment, but not all individuals have access, respond to treatment, or prefer this option because of stigma. Music therapy is effective for short-term anxiety reduction, but it is unknown whether it is noninferior to first-line CBT for long-term anxiety reduction.

METHODS: This comparative effectiveness trial randomly assigned English- or Spanish-speaking survivors of cancer to seven weekly telehealth sessions of music therapy or CBT. The coprimary end points were changes in the Hospital Anxiety and Depression Scale (HADS) anxiety score at weeks 8 …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Engaging Ukrainian Tf-Cbt Therapists In A Practice Skills Course To Support Their Wellbeing, Elisabeth Pollio, Esther Deblinger, Beth Cooper, Maike Garbade, Julie P Harrison, Elisa Pfeiffer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Burnout and secondary traumatic stress (STS) are common among therapists working with trauma-exposed clients, which can negatively impact them professionally and personally. The shared trauma of war exposure may put therapists at greater risk. To help support their wellbeing, an eight-session course was offered to Ukrainian therapists following training in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). This course involves therapists personally utilizing the PRACTICE skills taught to clients in TF-CBT for professional and personal benefit.

Objective: The objective was to gather preliminary evidence on the potential impact of implementing the course with Ukrainian therapists providing TF-CBT during a period of …

The Microstructure Of Metastatic Bone Lesions Suggests Tumor Mediated Alterations In Bone Mineralization, Hanwen Fan, Zhan Xu, Carla Berrospe Rodriguez, Noah Dover, Andrei Demkov, Morgan Lilly, Guillermo Aguilar, Larry J Suva, Xiang H-F Zhang, Yuxiao Zhou

Faculty, Staff and Students Publications

Breast, prostate and lung cancer cells frequently metastasize to bone, leading to disruption of the bone microstructure. This study utilized mechanical testing coupled with micro-CT imaging, digital volume correlation (DVC), and atomic force microscopy (AFM) nanomechanical testing to examine the mechanical property variations in mouse long bones (tibia) with metastatic lung cancer cell involvement, spanning from the whole-bone scale to the microstructural level. In addition, we also investigated how metastatic invasion alters the morphology of hydroxyapatite nanocrystals in bone at the nanometer scale. The biochemical composition within metastatic lesions was assessed using Raman spectroscopy and correlated with AFM mechanical testing …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Maitreyee Mohanty, Claudia Leiras, Haiyan Sun, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

Use Of An Expert Panel For Symptomatic Patients With Grade I Degenerative Lumbar Spondylolisthesis: A Randomized Clinical Trial, Zoher Ghogawala, Tasneem Rizvi, Zhibang Lin, Adam Kanter, Praveen Mummaneni, Erica Bisson, Todd Albert, Daniel Resnick, Michael Wang, Steven Glassman, David Polly, Mohamad Bydon, Subu Magge, Luis Tumialan, Michael Fehlings, Michael Steinmetz, Robert Whitmore, Vedantam Rajshekhar, James Harrop, Roger Härtl, Elnasri Ahmed, Dom Coric, Paul Mccormick, Richard Assaker, Abdul Msaddi, Langston Holly, Yoshiharu Kawaguchi, Asdrubal Falavigna, Fred Barker, Edward Benzel

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The appropriate utilization of lumbar fusion when performing laminectomy for lumbar spondylolisthesis is uncertain. The objective was to determine whether the use of a surgical expert review panel recommending fusion might improve patient selection, possibly reducing surgical failures.

METHODS: Randomized clinical trial of patients with symptomatic degenerative lumbar stenosis with spondylolisthesis enrolled from 14 North American hospitals was conducted with patients randomized to receive an expert panel review of their case or not. Spinal expert review consisted of 10 to 15 surgeons' review of patient images and clinical data with voting on the appropriateness of fusion. Primary …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Using Video Ethnography And Stimulated Recall Interviews To Describe The Diagnostic Process In The Emergency Department, Milisa Manojlovich, Caitlin Cassady, Sarah J Parker, Ellie Davis, Charlotte Ahr, David Ryamukuru, Anna Wang, Kalyan Pasupathy, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.

Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Centrally Inserted Central Catheter Placement Using A Novel, Handheld, Image-Guided, Robotic Device: Results Of Initial Feasibility Trial In Patients, James P Herlihy, William E Cohn, Adrian Ebner

Faculty, Staff and Students Publications

Background: Central venous access devices (CVADs) are an essential and widely used tool for the treatment of the critically ill, patients undergoing major surgery, and for many patients requiring hemodialysis. Automation of centrally inserted central catheters (CICCs) could potentially make CVAD placement safer, more effective, and more accessible. A new device that uses ultrasound image-guided, robotic needle placement, in addition to traditional Seldinger technique, to place a CICC is described.

Objective: The device was used in a small, first-in-human, trial for placing non-tunneled hemodialysis catheters (NTHDCs), in order to determine feasibility of clinical use.

Methods: Consecutive patients requiring a NTHDC, …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Examining The Relationship Between Dysphagia, Eating-Related Symptoms, And Diet Quality Among Oropharyngeal Cancer Patients During Critical Stages Of Cancer Survivorship: The U-Dine Study, Beatrice Manduchi, Vlad C Sandulache, Ji Yun Tark, Shreela Sharma, Ruosha Li, Emily Roller, Andrew Bevelhimer, Katherine A Hutcheson, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

Background: Diet quality is a modifiable factor impacting treatment outcomes in oropharyngeal cancer (OPC), yet the effect of dysphagia and self-reported eating-related symptoms remains unclear. This study examined their associations with diet quality in OPC patients.

Methods: A cross-sectional analysis was conducted with two parallel cohorts from MD Anderson Cancer Center and Michael E. DeBakey Veterans Affairs Medical Center as part of the Uncovering the Long-Term Impact of OPC and Dysphagia on Dietary Quality and Nutrition Among Cancer Survivors (U-DINE) Study. Participants at varying survivorship stages (prediagnosis, 3-6 and 18+ months posttreatment) were assessed for dysphagia (DIGEST scale) and six …

Observational Activation Of Anterior Cingulate Cortical Neurons Coordinates Hippocampal Replay In Social Learning, Xiang Mou, Daoyun Ji

Faculty, Staff and Students Publications

Social learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are reactivated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Upper Gastrointestinal Symptoms And Gulf War Illness In A Clinical Cohort Of Us Veterans: A Retrospective, Cross-Sectional Study, Abdelrahman Yousef, Sarah T Ahmed, Theresa H Nguyen Wenker, Alice B S Nono-Djotsa, Stephen H Boyle, Elizabeth J Gifford, Deeksha Malhotra, Helena Chandler, Sandhya Bandi, Drew A Helmer

Faculty, Staff and Students Publications

Objective: Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care.

Methods: This cross-sectional study analysed GWVs referred to a Veterans Health Administration clinical War-Related Illness and Injury Study Center (2008-2020). Symptoms, demographics, military service and clinical history were obtained from self-reported intake packets. GWI was defined by the Centers for Disease Control and Prevention criteria requiring moderate-to-severe symptoms …

Elephant Endotheliotropic Herpesvirus 2 Infection In 5 African Elephants (Loxodonta Africana) At Multiple North American Zoological Institutions, Taylor J Willis, Anne Burgdorf-Moisuk, Maren Connolly, Jan Raines, Cameron Ratliff, Zoltan S Gyimesi, Erica Lipanovich, Genevive A Dumonceaux, Kathryn L Perrin, Lauren L Howard, Matthew E Kinney, Kirk Suedmeyer, Erin Latimer, Tiffany L Kim, Jessica R Watts, Jie Tan, Paul Ling

Faculty, Staff and Students Publications

Objective: To acknowledge that elephant endotheliotropic herpesvirus (EEHV) is a well-recognized major threat to Asian elephants (Elephas maximus) and can cause acute and often fatal hemorrhagic disease (HD). Historically, EEHV-HD has been less frequently identified in African elephants (Loxodonta africana). This case series describes 5 recent cases of EEHV2 infection in African elephants within managed care at 5 North American institutions.

Animals: 5 African elephants (L africana).

Clinical presentation: The cases involved 4-, 7-, and 10-year-old males that died despite receiving aggressive medical therapy and 4- and 14-year-old females that survived. Clinical signs included lethargy, decreased appetite, lameness, changes in …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

Outcomes Of Brexucabtagene Autoleucel In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia With Cns Involvement, Ibrahim N Muhsen, Gregory W Roloff, Rawan Faramand, Tamer Othman, Yannis Valtis, Noam E Kopmar, Simone E Dekker, Matthew Connor, Santiago Mercadal, Timothy E O'Connor, Kaitlyn C Dykes, Mohamed Ahmed, Nikeshan Jeyakumar, Amy Zhang, Katharine Miller, Katherine C Sutherland, Caitlin Guzowski, Vishal K Gupta, Navneet Majhail, Minoo Battiwalla, Melhem M Solh, Shahbaz A Malik, John Mathews, Caspian H Oliai, Paul Shaughnessy, Luke Mountjoy, Catherine J Lee, Aaron C Logan, Stephanie B Tsai, Jessica T Leonard, Marc Schwartz, Joshua P Sasine, Muthu Kumaran, Noelle Frey, Jae H Park, Divya Koura, Ryan D Cassaday, Bijal D Shah, Ibrahim Aldoss, Lori S Muffly, Laquisa C Hill

Faculty, Staff and Students Publications

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 …

Placental Polycyclic Aromatic Hydrocarbon (Pah) Levels Are Associated With Spontaneous Preterm Birth, Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D Shope, Joseph Hagan, Kjersti M Aagaard, Bhagavatula Moorthy, Melissa A Suter

Faculty, Staff and Students Publications

While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from …

Targeting Sting To Disrupt Macrophage-Mediated Adhesion In Encapsulating Peritoneal Sclerosis, Juan Sun, Yuxiang Sun, Dandan Guo, Huolin Ye, Qiang Huang, Hu Zhou, Canming Li, Mei Liao, Yujia You, Hongli Shang, Pan Zhou, Dongxuan Wu, Janusz Witowski, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced …