Medicine and Health Sciences Commons^™

Comprehensive Molecular Profiling Of Multiple Myeloma Identifies Refined Copy Number And Expression Subtypes, Sheri Skerget, Ravi Vij, Et Al.

2020-Current year OA Pubs

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are …

A Novel Antigen Biomarker For Detection Of High-Level Of Loa Loa Microfilaremia, Sarah E Greene, Yuefang Huang, Kerstin Fischer, Bruce A. Rosa, John Martin, Makedonka Mitreva, Devyn Yates, Samuel Wanji, Joseph Kamgno, Philip J. Budge, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region.

METHODS AND FINDINGS: We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development …

Pulmonary Cellular Toxicity In Alpha-1 Antitrypsin Deficiency, Kristine M Abo, Carly Merritt, Maria C Basil, Susan M Lin, Edward Cantu, Michael P Morley, Pushpinder Bawa, Marissa Gallagher, Derek E Byers, Edward E Morrisey, Andrew A Wilson

2020-Current year OA Pubs

No abstract provided.

Loss Of Periostin Function Impairs Ligament Fibroblast Activity And Facilitates Ros-Mediated Cellular Senescence, Muhammad Farooq Rai, Xin Duan, Mingming Yan, Robert H Brophy, Lei Cai

2020-Current year OA Pubs

Anterior cruciate ligament (ACL) injuries pose a significant challenge due to their limited healing potential, often resulting in premature arthritis. The factors and mechanisms contributing to this inadequate healing process remain elusive. During the acute phase of injury, ACL tissues express elevated periostin levels that decline over time. The functional significance of periostin in ligament biology remains understudied. In this study, we investigated the functional and mechanistic implications of periostin deficiency in ACL biology, utilizing ligament fibroblasts derived from patients and a murine model of ACL rupture. Our investigations unveiled that periostin knockdown compromised fibroblast growth characteristics, hindered the egress …

The Placement Of A Single-Incision Mini-Sling For The Treatment Of Complete Intrinsic Sphincter Deficiency In An Adolescent Female: A Case Report, Norman Bebla, Dylan Gallegos

HCA Healthcare Journal of Medicine

Introduction

Intrinsic sphincter deficiency (ISD) is associated with a patient history of urethral injury or childbirth. Suburethral sling placement for ISD has been found to be beneficial in patients with this diagnosis. ISD in the pediatric population is rare and surgical management may prove difficult. ISD requires intensive counseling on available treatment options for this unique population.

Case Presentation

This report is on the use of the single-incision mini-sling for complete ISD in an adolescent patient. The patient was a 15-year-old nulligravid female who was found to have idiopathic complete intrinsic deficiency based on a multi-channel urodynamic study. Despite conservative …

Comprehensive Analysis Of Substernal Lead Removal: Experience From Ev Icd Pilot, Pivotal, And Continued Access Studies., Venkata Sagi, Francis Murgatroyd, Lucas V A Boersma, Jaimie Manlucu, Bradley P Knight, Christophe Leclercq, Anish Amin, Ulrika Maria Birgersdotter-Green, Joseph Yat Sun Chan, Henri Roukoz, Mauro Biffi, Haris Haqqani, Russell Denman, Christopher Wiggenhorn, Thomas R Holmes, Thomas Lulic, Paul Friedman, Ian Crozier

Heart and Vascular Articles

AIMS: The extravascular implantable cardioverter-defibrillator (EV ICD) has been shown to be safe and effective for patients at risk of sudden cardiac death, but little is known about EV ICD lead removal in humans. This analysis aimed to characterize the EV ICD lead removal experience thus far.

METHODS AND RESULTS: This was a retrospective analysis of lead removals from the EV ICD Pilot, Pivotal, and Continued Access Studies. Patients with a successful EV ICD implant who underwent lead removal were included. The main objective was lead removal success. Ancillary objectives included characterizing technique used, procedure complications, and reimplantation status. An …

Brief Report: Incidence And Outcomes Of Pediatric Tracheal Intubation-Associated Cardiac Arrests In The Icu-Resus Clinical Trial, Akira Nishisaki, Stuart H Friess, Arushi Manga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Tracheal intubation (TI)-associated cardiac arrest (TI-CA) occurs in 1.7% of pediatric ICU TIs. Our objective was to evaluate resuscitation characteristics and outcomes between cardiac arrest patients with and without TI-CA.

METHODS: Secondary analysis of cardiac arrest patients in both ICU-RESUS trial and ancillary CPR-NOVA study. The primary exposure was TI-CA, defined as cardiac arrest occurred during TI procedure or within 20 min after endotracheal tube placement. The primary outcome was survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged).

RESULTS: Among 315 children with cardiac arrests, 48 (15.2%) met criteria for TI-CA. …

Identification Of A0 Minimum Ablative Margins For Colorectal Liver Metastases: Multicentre, Retrospective Study Using Deformable Ct Registration And Artificial Intelligence-Based Autosegmentation, Iwan Paolucci, Jessica Albuquerque Marques Silva, Yuan-Mao Lin, Gregor Laimer, Valentina Cignini, Francesca Menchini, Marcio Meira, Alexander Shieh, Caleb O'Connor, Kyle A Jones, Carlo Gazzera, Paolo Fonio, Kristy K Brock, Marco Calandri, Marcos Menezes, Reto Bale, Bruno C Odisio

Faculty, Staff and Student Publications

Background: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting.

Methods: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Brief Report: Incidence And Outcomes Of Pediatric Tracheal Intubation-Associated Cardiac Arrests In The Icu-Resus Clinical Trial, Akira Nishisaki, Ron Reeder, Elizabeth Laverriere Mcgovern, Tageldin Ahmed, Michael Bell, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph Carcillo, Todd Carpenter, Wesley Diddle, Myke Federman, Ericka Fink, Deborah Franzon, Aisha Frazier, Stuart Friess, Kathryn Graham, Mark Hall, David Hehir, Christopher M Horvat, Leanna Huard, Tensing Maa, Arushi Manga, Patrick Mcquillen, Kathleen Meert, Ryan Morgan, Peter Mourani, Vinay Nadkarni, Maryam Naim, Daniel Notterman, Chella Palmer, Anil Sapru, Carleen Schneiter, Matthew Sharron, Neeraj Srivastava, Shirley Viteri, David Wessel, Heather Wolfe, Andrew Yates, Athena Zuppa, Robert Sutton, Robert Berg

Department of Pediatrics Faculty Papers

BACKGROUND: Tracheal intubation (TI)-associated cardiac arrest (TI-CA) occurs in 1.7% of pediatric ICU TIs. Our objective was to evaluate resuscitation characteristics and outcomes between cardiac arrest patients with and without TI-CA.

METHODS: Secondary analysis of cardiac arrest patients in both ICU-RESUS trial and ancillary CPR-NOVA study. The primary exposure was TI-CA, defined as cardiac arrest occurred during TI procedure or within 20 min after endotracheal tube placement. The primary outcome was survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged).

RESULTS: Among 315 children with cardiac arrests, 48 (15.2%) met criteria for TI-CA. …

Persistent Mri Findings Unique To Blast And Repetitive Mild Tbi: Analysis Of The Cenc/Limbic Cohort Injury Characteristics, David F Tate, Benjamin S C Wade, Carmen S Velez, Erin D Bigler, Nicholas D Davenport, Emily L Dennis, Carrie Esopenko, Sidney R Hinds, Jacob Kean, Eamonn Kennedy, Kimbra Kenney, Andrew R Mayer, Mary R Newsome, Carissa L Philippi, Mary J Pugh, Randall S Scheibel, Brian A Taylor, Maya Troyanskaya, John K Werner, Gerald E York, William Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

Introduction: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements.

Material and methods: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium …

Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan

Faculty, Staff and Students Publications

Introduction: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood.

Materials and methods: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function.

Results: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age …

Cognitive Effects Of Simulated Galactic Cosmic Radiation Are Mediated By Apoe Status, Sex, And Environment In App Knock-In Mice, Laura Wieg, Jason C Ciola, Caroline C Wasén, Fidelia Gaba, Brianna R Colletti, Maren K Schroeder, Robert G Hinshaw, Millicent N Ekwudo, David M Holtzman, Takashi Saito, Hiroki Sasaguri, Takaomi C Saido, Laura M Cox, Cynthia A Lemere

2020-Current year OA Pubs

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer's disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APP

Detection Of Distant Relatedness In Biobanks To Identify Undiagnosed Cases Of Mendelian Disease As Applied To Long Qt Syndrome, Megan C Lancaster, Hung-Hsin Chen, M Benjamin Shoemaker, Matthew R Fleming, Teresa L Strickland, James T Baker, Grahame F Evans, Hannah G Polikowsky, David C Samuels, Chad D Huff, Dan M Roden, Jennifer E Below

Faculty, Staff and Student Publications

Rare genetic diseases are typically studied in referral populations, resulting in underdiagnosis and biased assessment of penetrance and phenotype. To address this, we develop a generalizable method of genotype inference based on distant relatedness and deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population. We identify 9 LQT5 families referred to a single specialty clinic, each carrying p.Asp76Asn, the most common LQT5 variant. We uncover recent common ancestry and a single shared haplotype among probands. Application to a non-referral population of 69,819 BioVU biobank subjects identifies 22 additional subjects sharing this …

A Non-Parametric Approach To Predict The Recruitment For Randomized Clinical Trials: An Example In Elderly Inpatient Settings, Alejandro Villasante-Tezanos, Yong-Fang Kuo, Christopher Kurinec, Yisheng Li, Xiaoying Yu

Faculty, Staff and Student Publications

BACKGROUND: Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement.

METHODS: We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

Novel Framework Of Financial Hardship In Childhood Cancer: Incorporating Stakeholder Perspectives, Julie Ritter, Sara M Malone, Et Al.

2020-Current year OA Pubs

PURPOSE: Although financial hardship in childhood cancer contributes to poor outcomes, no standardized tool to assess its impact exists. Existing methods are heterogeneous and designed using high-income country (HIC), adult perspectives. This project aimed to construct a stakeholder-informed conceptual framework of financial hardship in childhood cancer with global relevancy.

METHODS: Group concept mapping, a participatory mixed-methods approach, was used. Participants were parents or caregivers of a child with cancer, childhood cancer survivors, and clinical or nonclinical support personnel, fluent in English, Spanish, or Portuguese. A representative panel established a comprehensive list of relevant items. Participants individually sorted these items into …

Contrast Enhanced Ultrasound Of Liver Lesions In Patients Treated For Childhood Malignancies., Ayatullah Mostafa, Zachary Abramson, Mina Ghbrial, Som Biswas, Sherwin S. Chan, Himani Darji, Jessica Gartrell, Seth E. Karol, Yimei Li, Daniel A. Mulrooney, Tushar Patni, Tarek M. Zaghloul, M Beth Mccarville

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients treated for cancer have a higher incidence of focal liver lesions than the general population and there is often concern for a malignant etiology. This can result in patient, caregiver and physician anxiety and is managed by a "wait and watch" approach, or immediate additional imaging, or biopsy, depending on the degree of clinical concern. Because it is a low-cost, easily accessible, radiation and sedation free modality, we investigated the value of contrast enhanced ultrasound (CEUS) to accurately distinguish benign from malignant liver lesions in patients treated for childhood malignancies.

METHODS: We performed an IRB approved retrospective study …

Milvexian Vs Apixaban For Stroke Prevention In Atrial Fibrillation: The Librexia Atrial Fibrillation Trial Rationale And Design, Sneha S Jain, Kenneth W Mahaffey, Karen S Pieper, Wataru Shimizu, Tatjana Potpara, Christian T Ruff, Hooman Kamel, Basil S Lewis, Jan H Cornel, Peter R. Kowey, Jay Horrow, John Strony, Alexei N Plotnikov, Danshi Li, Stephen Weng, Julia Donahue, C Michael Gibson, P Gabriel Steg, Roxana Mehran, Jeffrey I Weitz, S Claiborne Johnston, Graeme J Hankey, Robert A Harrington, Carolyn S P Lam

Department of Medicine Faculty Papers

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.

METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …

Systematic Transcriptomic Analysis Of Childhood Medulloblastoma Identifies N6-Methyladenosine-Dependent Lncrna Signatures Associated With Molecular Subtype, Immune Cell Infiltration, And Prognosis, Kandarp Joshi, Menglang Yuan, Keisuke Katsushima, Olivier Saulnier, Animesh Ray, Ernest Amankwah, Stacie Stapleton, George Jallo, Michael D Taylor, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Medulloblastoma, the most common malignant pediatric brain tumor, is classified into four main molecular subgroups, but group 3 and group 4 tumors are difficult to subclassify and have a poor prognosis. Rapid point-of-care diagnostic and prognostic assays are needed to improve medulloblastoma risk stratification and management. N6-methyladenosine (m6A) is a common RNA modification and long non-coding RNAs (lncRNAs) play a central role in tumor progression, but their impact on gene expression and associated clinical outcomes in medulloblastoma are unknown. Here we analyzed 469 medulloblastoma tumor transcriptomes to identify lncRNAs co-expressed with m6A regulators. Using LASSO-Cox analysis, we identified a five-gene …

Donor Types And Outcomes Of Transplantation In Myelofibrosis: A Cibmtr Study, Tania Jain, Noel Estrada-Merly, M Queralt Salas, Soyoung Kim, Jakob Devos, Min Chen, Xi Fang, Rajat Kumar, Marcio Andrade-Campos, Hany Elmariah, Vaibhav Agrawal, Mahmoud Aljurf, Ulrike Bacher, Talha Badar, Sherif M Badawy, Karen Ballen, Amer Beitinjaneh, Vijaya Raj Bhatt, Christopher Bredeson, Zachariah Defilipp, Bhagirathbhai Dholaria, Nosha Farhadfar, Shatha Farhan, Arpita P Gandhi, Siddhartha Ganguly, Usama Gergis, Michael R Grunwald, Nada Hamad, Betty K Hamilton, Yoshihiro Inamoto, Madiha Iqbal, Omer Jamy, Mark Juckett, Mohamed A Kharfan-Dabaja, Maxwell M Krem, Deepesh P Lad, Jane Liesveld, Monzr M Al Malki, Adriana K Malone, Hemant S Murthy, Guillermo Ortí, Sagar S Patel, Attaphol Pawarode, Miguel-Angel Perales, Marjolein Van Der Poel, Olle Ringden, David A Rizzieri, Alicia Rovó, Bipin N Savani, Mary Lynn Savoie, Sachiko Seo, Melhem Solh, Celalettin Ustun, Leo F Verdonck, John R Wingard, Baldeep Wirk, Nelli Bejanyan, Richard J Jones, Taiga Nishihori, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, Vikas Gupta

Department of Medical Oncology Faculty Papers

We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched …

Multicenter, Phase 1 Study Of Etavopivat (Ft-4202) Treatment For Up To 12 Weeks In Patients With Sickle Cell Disease, Santosh L Saraf, Robert Hagar, Modupe Idowu, Ifeyinwa Osunkwo, Kimberly Cruz, Frans A Kuypers, R Clark Brown, James Geib, Maria Ribadeneira, Patricia Schroeder, Eric Wu, Sanjeev Forsyth, Patrick F Kelly, Theodosia A Kalfa, Marilyn J Telen

Faculty, Staff and Student Publications

Etavopivat is an investigational, once daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: 1 single-dose, 2 multiple ascending doses, and 1 open-label (OL). In the OL cohort, 15 patients (median age 33.0 years [range, 17-55]) received 400 mg etavopivat once daily for 12 weeks; 14 patients completed treatment. Consistent with the mechanism of PKR activation, increases in adenosine triphosphate and decreases in 2,3-diphosphoglycerate were observed and sustained over …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Raphael Mwangi, Loretta J Nastoupil, Patrick M Reagan, Umar Farooq, Jason T Romancik, Timothy J Mcdonnell, Shaun M Riska, Lzidore S Lossos, Brad S Kahl, Peter Martin, Thomas E Witzig, James R Cerhan, Christopher R Flowers, Grzegorz S Nowakowski, Matthew J Maurer

Faculty, Staff and Student Publications

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …

Evaluating The Impact Of Laboratory-Based Eligibility Criteria By Race/Ethnicity In First-Line Clinical Trials Of Dlbcl, Arushi Khurana, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, …

Single-Cell Analysis Of Chromatin And Expression Reveals Age- And Sex-Associated Alterations In The Human Heart, David F Read, Yiing Lin, Et Al.

2020-Current year OA Pubs

Sex differences and age-related changes in the human heart at the tissue, cell, and molecular level have been well-documented and many may be relevant for cardiovascular disease. However, how molecular programs within individual cell types vary across individuals by age and sex remains poorly characterized. To better understand this variation, we performed single-nucleus combinatorial indexing (sci) ATAC- and RNA-Seq in human heart samples from nine donors. We identify hundreds of differentially expressed genes by age and sex and find epigenetic signatures of variation in ATAC-Seq data in this discovery cohort. We then scale up our single-cell RNA-Seq analysis by combining …

Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris

Faculty, Staff and Students Publications

AIMS: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

METHODS AND RESULTS: We included patientsMFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman …

Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy In India: A Convergent Parallel Mixed Methods Study, Anubha Agarwal, Raji Devarajan, Salva Balbale, Aashima Chopra, Dorairaj Prabhakaran, Mark D Huffman, Lisa R Hirschhorn, Padinhare P Mohanan

2020-Current year OA Pubs

INTRODUCTION: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally.

METHODS: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated …

Utilization Of A Novel Scoring System In Predicting 30-Day Mortality In Acute Pulmonary Embolism, The Clot-5 Pilot Study, Alexandru Marginean, Punit Arora, Kevin Walsh, Elizabeth Bruno, Cathryn Sawalski, Riya Gupta, Frances Greathouse, Jacob Clarke, Quinn Mallery, Myoung Hyun Choi, Waddah Malas, Parth Shah, David Sutherland, Amudha Kumar, Igor Wroblewski, Ahmed Elkaryoni, Parth Desai, Yevgeniy Brailovsky, Amir Darki

Division of Cardiology Faculty Papers

OBJECTIVES: To construct a new scoring system utilizing biomarkers, vitals, and imaging data to predict 30-day mortality in acute pulmonary embolism (PE).

BACKGROUND: Acute PE, a well-known manifestation of venous thromboembolic disease, is responsible for over 100,000 deaths worldwide yearly. Contemporary management algorithms rely on a multidisciplinary approach to care via PE response teams (PERT) in the identification of low, intermediate, and high-risk patients. The PESI and sPESI scores have been used as cornerstones of the triage process in assigning risk of 30-day mortality for patients presenting with acute PE; however, the specificity of these scoring systems has often come …