Digital Commons Network^™

Ion Suppression Correction And Normalization For Non-Targeted Metabolomics, Iqbal Mahmud, Bo Wei, Lucas Veillon, Lin Tan, Sara Martinez, Bao Tran, Alexander Raskind, Felice De Jong, Yiwei Liu, Jibin Ding, Yun Xiong, Wai-Kin Chan, Rehan Akbani, John N Weinstein, Chris Beecher, Philip L Lorenzi

Faculty, Staff and Student Publications

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and sensitivity. Here we report a method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) library plus companion algorithms to: 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We evaluate the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reversed-phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range …

Estrogen Receptor-Α Ablation Reverses Muscle Fibrosis And Inguinal Hernias, Tanvi Potluri, Tianming You, Ping Yin, John Coon, Jonah J Stulberg, Yang Dai, David J Escobar, Richard L Lieber, Hong Zhao, Serdar E Bulun

Faculty, Staff and Student Publications

Fibrosis of the lower abdominal muscle (LAM) contributes to muscle weakening and inguinal hernia formation, an ailment that affects a noteworthy 50% of men by age 75 and necessitates surgical correction as the singular therapy. Despite its prevalence, the mechanisms driving LAM fibrosis and hernia development remain poorly understood. Using a humanized mouse model that replicates the elevated skeletal muscle tissue estrogen concentrations seen in aging men, we identified estrogen receptor-α (ESR1) as a key driver of LAM fibroblast proliferation, extracellular matrix deposition, and hernia formation. Fibroblast-specific ESR1 ablation effectively prevented muscle fibrosis and herniation, while pharmacological ESR1 inhibition with …

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial., Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson

Heart and Vascular Articles

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Sleep-Wake Variation In Body Temperature Regulates Tau Secretion And Correlates With Csf And Plasma Tau, Geoffrey Canet, Brendan P. Lucey, Et Al.

2020-Current year OA Pubs

Sleep disturbance is bidirectionally associated with an increased risk of Alzheimer's disease and other tauopathies. While the sleep-wake cycle regulates interstitial and cerebrospinal fluid (CSF) tau levels, the underlying mechanisms remain unknown. Understanding these mechanisms is crucial, given the evidence that tau pathology spreads through neuron-to-neuron transfer, involving the secretion and internalization of pathological tau forms. Here, we combined in vitro, in vivo, and clinical methods to reveal a pathway by which changes in body temperature (BT) over the sleep-wake cycle modulate extracellular tau levels. In mice, a higher BT during wakefulness and sleep deprivation increased CSF and plasma tau …

Retinoic Acid Antagonizes Estrogen Signaling To Maintain Adult Uterine Cell Fate, Yan Yin, Meade Haller, Lauren Goldinger, Shivani Bharadwaj, Emily So, Vivian Robles-Pinos, David Chen, Liang Ma

2020-Current year OA Pubs

Classical tissue recombination experiments demonstrate that cell-fate determination along the anterior-posterior axis of the Müllerian duct occurs prior to postnatal day 7 in mice. However, little is known about how these cell types are maintained in adults. In this study, we provide genetic evidence that a balance between antagonistic retinoic acid (RA) and estrogen signaling activity is required to maintain simple columnar cell fate in adult uterine epithelium. Transdifferentiation of simple columnar uterine epithelium into stratified cervicovaginal-like epithelium was observed in three related mouse genetic models, in which RA signaling was perturbed in the postnatal uterus. Single-cell RNA sequencing analysis …

Characterization Of The Vaginal Microbiome Of Postmenopausal Patients Receiving Chemoradiation For Locally Advanced Cervical Cancer, Brett A. Tortelli, Jessika Contreras, Stephanie Markovina, Li Ding, Kristine M. Wylie, Julie K. Schwarz

2020-Current year OA Pubs

The standard-of-care treatment of locally advanced cervical cancer includes pelvic radiation therapy with concurrent cisplatin-based chemotherapy and is associated with a 30%-50% failure rate. New prognostic and therapeutic targets are needed to improve clinical outcomes. The vaginal microbiome has been linked to the pathogenesis of cervical cancer, but little is known about the vaginal microbiome in locally advanced cervical cancer as it relates to chemoradiation. In this pilot study, we utilized 16S rRNA gene community profiling to characterize the vaginal microbiomes of 26 postmenopausal women with locally advanced cervical cancer receiving chemoradiation. Our analysis revealed diverse anaerobe-dominated communities whose taxonomic …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

Combined Clinical, Structural And Cellular Studies Discriminate Pathogenic And Benign Trpv4 Variants, Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A Mccray

Faculty, Staff and Students Publications

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 …

A Comprehensive Head-To-Head Comparison Of Key Plasma Phosphorylated Tau 217 Biomarker Tests, Noëlle Warmenhoven, Nicolas R Barthélemy, Suzanne E Schindler, Andrew J Aschenbrenner, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Laura Ibanez, Jigyasha Timsina, Carlos Cruchaga, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests. Samples from 998 individuals [mean (range) age 68.5 (20.0-92.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and …

Racial Differences In Ctdna Profiles, Targeted Therapy Use, And Outcomes In Metastatic Breast Cancer, Emily L Podany, Katherine Clifton, Shaili Tapiavala, Foluso O Ademuyiwa, Cynthia X Ma, Andrew A Davis, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment.

OBJECTIVES: To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included.

EXPOSURES: Targeted treatment …

Cardiovascular Disease In Adults With Osteogenesis Imperfecta: Clinical Characteristics, Care Recommendations, And Research Priorities Identified Using A Modified Delphi Technique, Lars Folkestad, Siddharth K Prakash, Sandesh C S Nagamani, Niels Holmark Andersen, Erin Carter, Jannie Dahl Hald, Riley J Johnson, Bente Langdahl, Eleanor M Perfetto, Cathleen Raggio, Stuart H Ralston, Robert A Sandhaus, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Student Publications

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the …

Arginine Metabolism Is A Biomarker Of Red Blood Cell And Human Aging., Julie A Reisz, Eric J Earley, Travis Nemkov, Alicia Key, Daniel Stephenson, Gregory R Keele, Monika Dzieciatkowska, Steven L Spitalnik, Eldad A Hod, Steven Kleinman, Nareg H Roubinian, Mark T Gladwin, Kirk C Hansen, Philip J Norris, Michael P Busch, James C Zimring, Gary Churchill, Grier P Page, Angelo D'Alessandro

Faculty Research 2025

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and …

Polyploid Superficial Uroepithelial Bladder Barrier Cells Express Features Of Cellular Senescence Across The Lifespan And Are Insensitive To Senolytics., Iman M Al-Naggar, Maria Antony, Dylan Baker, Lichao Wang, Lucas Da Cunha Godoy, Chia-Ling Kuo, Matthew O Fraser, Phillip P Smith, Ming Xu, George A Kuchel

Faculty Research 2025

Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging-related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal …

Subendocardial Ischemia: Does Cmd Really Exist?, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress. Second, rare patients indeed have ischemic signs or symptoms due solely to reduced flow attributable to …

The Wellness Connection February 2025, Roger Williams University School Of Law Office Of Student Life

Life of the Law School (1993- )

No abstract provided.

Respiratory Syncytial Virus Disease Burden And Nirsevimab Effectiveness In Young Children From 2023-2024, Heidi L Moline, Ariana P Toepfer, Ayzsa Tannis, Geoffrey A Weinberg, Mary A Staat, Natasha B Halasa, Julie A Boom, Eileen J Klein, John V Williams, Jennifer E Schuster, Leah Goldstein, Erin R Mckeever, Casey Kalman, Clinton Paden, Lydia Atherton, Megha Aggarwal, Pavitra Roychoudhury, Pedro A Piedra, Leila C Sahni, Laura S Stewart, Rangaraj Selvarangan, Marian G Michaels, Elizabeth P Schlaudecker, Peter G Szilagyi, Janet A Englund, Benjamin R Clopper, Natalie J Thornburg, Gordana Derado, Meredith L Mcmorrow, Fatimah S Dawood, New Vaccine Surveillance Network Collaborators

Faculty, Staff and Students Publications

Importance: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness.

Objective: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Characterizing Prodrome (Premonitory Phase) In Migraine: Results From The Prodrome Trial Screening Period, Todd Schwedt, Richard Lipton, Peter Goadsby, Chia-Chun Chiang, Brad Klein, Cory Hussar, Chengcheng Liu, Sung Yun Yu, Michelle Finnegan, Joel Trugman

College of Nursing Faculty Papers & Presentations

BACKGROUND AND OBJECTIVE: Limited data are available describing the frequency, severity, and consistency of prodromal symptoms followed by headache. This analysis of the PRODROME trial screening period characterized prodromal symptoms in people with migraine, including the most common symptoms and their severity, and the frequency and consistency with which prodromal symptoms were followed by headache.

METHODS: PRODROME was a multicenter, randomized, double-blind, placebo-controlled, crossover trial conducted in the United States that enrolled adults with 2-8 migraine attacks per month who stated they could identify prodromal symptoms that were reliably followed by a headache. The trial included a 60-day screening period …

Plasma Proteomic Characterization Of Motoric Cognitive Risk And Mild Cognitive Impairment, Gabriela T Gomez, Sanish Sathyan, Jingsha Chen, Myriam Fornage, Pascal Schlosser, Zhongsheng Peng, Jenifer Cordon, Priya Palta, Kevin J Sullivan, Adrienne Tin, B Gwen Windham, Rebecca F Gottesman, Nir Barzilai, Sofiya Milman, Joe Verghese, Josef Coresh, Keenan A Walker

Faculty, Staff and Student Publications

INTRODUCTION: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

METHODS: Participants were classified as MCR using a memory questionnaire and 4-meter walk. We measured 4877 plasma proteins collected during late-life and midlife. Multivariable logistic regression related each protein to late-life MCR/MCI. MCR-associated proteins were replicated internally at midlife and in an external cohort.

RESULTS: Proteome-wide analysis (n = 4076) identified 25 MCR-associated proteins. Eight of these proteins remained associated with late-life MCR …

Status Of Abortion Curriculum In Genetic Counseling: Survey Of Graduate Programs And Recent Graduates In The United States, Gina Sanchez, S Shahrukh Hashmi, Erica Bednar, Sarah Horvath, Bhavik Kumar, Katelynn Sagaser, Claire N Singletary, Aarti Ramdaney

Faculty, Staff and Student Publications

Genetic counselors (GCs) are trained to help individuals navigate the medical and psychological implications of genetic test results, familial conditions, and ultrasound anomalies. Therefore, familiarity with reproductive options, including abortion, is vital. However, previous studies have found gaps in GCs' knowledge regarding abortion care and there are currently no recommendations regarding abortion curriculum. This study aimed to assess the state of abortion curriculum in genetic counseling graduate programs in the United States and to examine and compare the satisfaction levels of program representatives and recent graduates. Program representatives and recent graduates were invited to complete an anonymous survey evaluating the …

Human Hypofunctional Ncf1 Variants Promote Pulmonary Fibrosis In The Bleomycin-Induced Mouse Model And Patients With Systemic Sclerosis Via Expansion Of Spphuman Hypofunctional Ncf1 Variants Promote Pulmonary Fibrosis In The Bleomycin-Induced Mouse Model And Systemic Sclerosis Patients Via Expansion Of Spp1+ Monocytes-Derived Macrophages, Xinran Yuan, Xiaodong Qin, Kenji Takemoto, Jian Zhao, Matthew Sanderson, Xue Xu, Yu Zhang, Kristi L Helke, Bethany Jacobs Wolf, Joel M Guthridge, Judith A James, Xiaodong Zhou, Shervin Assassi, Carol Feghali-Bostwick, Dandan Wang, Lingyun Sun, Betty P Tsao

Faculty, Staff and Student Publications

Objective: We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc).

Methods: Association of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight.

Results: The NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated …

Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla

Faculty, Staff and Student Publications

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with …

Obesity Predisposes Anthracycline-Treated Survivors Of Childhood And Adolescent Cancers To Subclinical Cardiac Dysfunction, Ian A George, Brianna Souder, Amy Berkman, David H Noyd, M Jay Campbell, Piers C A Barker, Michael Roth, Michelle A T Hildebrandt, Kevin C Oeffinger, Andrew W Mccrary, Andrew P Landstrom

Faculty, Staff and Student Publications

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …

Best Practices For Delivering Neoadjuvant Therapy In Pancreatic Ductal Adenocarcinoma, Jordan M Cloyd, Angela Sarna, Matthew J Arango, Susan E Bates, Manoop S Bhutani, Mark Bloomston, Vincent Chung, Efrat Dotan, Cristina R Ferrone, Patricia F Gambino, Ajit H Goenka, Karyn A Goodman, William A Hall, Jin He, Melissa E Hogg, Shiva Jayaraman, Avinash Kambadakone, Matthew H G Katz, Alok A Khorana, Andrew H Ko, Eugene J Koay, David A Kooby, Somashekar G Krishna, Liliana K Larsson, Richard T Lee, Anirban Maitra, Nader N Massarweh, Sameh Mikhail, Mahvish Muzaffar, Eileen M O'Reilly, Manisha Palta, Maria Q B Petzel, Philip A Philip, Marsha Reyngold, Daniel Santa Mina, Davendra P S Sohal, Tilak K Sundaresan, Susan Tsai, Kea L Turner, Timothy J Vreeland, Steve Walston, M Kay Washington, Terence M Williams, Jennifer Y Wo, Rebecca A Snyder

Faculty, Staff and Student Publications

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Design, setting, and participants: This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Daxibotulinumtoxina For Injection For The Treatment Of Upper Limb Spasticity In Adults After Stroke Or Traumatic Brain Injury, Atul T Patel, Michael C Munin, Ziyad Ayyoub, Gerard E Francisco, Rashid Kazerooni, Todd M Gross

Faculty, Staff and Student Publications

Background: Intramuscular injection of botulinum toxin type A is a first-line pharmacotherapy for adults with upper limb spasticity (ULS). However, reemergence of symptoms within 12 weeks of treatment is common and longer-lasting treatments are needed.

Objective: To evaluate the efficacy and safety of three doses of DaxibotulinumtoxinA for Injection (DAXI) for treatment of ULS in adults with stroke or traumatic brain injury.

Intervention: Intramuscular injections of placebo (N = 24), DAXI 250 U (N = 22), DAXI 375 U (N = 19), or DAXI 500 U (N = 18) to the suprahypertonic muscle (SMG) and other muscle groups.

Design: Randomized, …

Comparing One Stage, Chromogenic Assay Results And Discrepancies With Bleeding Phenotype And Genetic Variants In Females With Hemophilia A, Lakshmi Srivaths, Joanna Larson, Sepideh Saroukhani, Mohammed Said, Deborah Brown, Nidra Rodriguez, Neethu Menon, Miguel Escobar

Faculty, Staff and Student Publications

Background: Increasing evidence in females with hemophilia A has shown significant bleeding symptoms. Accurate factor (F) VIII activity (FVIII:C) measurement is essential to assign correct diagnosis and severity. Assay discrepancies reported in male patients with hemophilia A are not well studied in females.

Objectives: Our research sought to assess the association of FVIII:C levels by one-stage versus chromogenic assays and the assay discrepancy with bleeding phenotype and genetic mutation in females with hemophilia A.

Methods: Data from 64 females with hemophilia A from our center were reviewed with center's institutional review board approval. Descriptive statistics, chi-squared, Fisher's exact, and Bland-Altman …

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …