Medicine and Health Sciences Commons^™

Patient Safety And Artificial Intelligence In Clinical Care, Raj M Ratwani, David W Bates, David C Classen

Faculty, Staff and Students Publications

No abstract provided.

Chronic Respiratory Symptoms Following Deployment-Related Occupational And Environmental Exposures Among Us Veterans, Eric Garshick, Carrie A Redlich, Anna Korpak, Andrew K Timmons, Nicholas L Smith, Karen Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Kuschner, Octavian Ioachimescu, Michael Jerrett, Phillipe R Montgrain, Susan P Proctor, Emily S Wan, Christine H Wendt, Cherry Wongtrakool, Paul D Blanc

Faculty, Staff and Students Publications

Objectives: Characterise inhalational exposures during deployment to Afghanistan and Southwest Asia and associations with postdeployment respiratory symptoms.

Methods: Participants (n=1960) in this cross-sectional study of US Veterans (Veterans Affairs Cooperative Study 'Service and Health Among Deployed Veterans') completed an interviewer-administered questionnaire regarding 32 deployment exposures, grouped a priori into six categories: burn pit smoke; other combustion sources; engine exhaust; mechanical and desert dusts; toxicants; and military job-related vapours gas, dusts or fumes (VGDF). Responses were scored ordinally (0, 1, 2) according to exposure frequency. Factor analysis supported item reduction and category consolidation yielding 28 exposure items in 5 categories. Generalised …

Targeting Alk Averts Ribonuclease 1-Induced Immunosuppression And Enhances Antitumor Immunity In Hepatocellular Carcinoma, Chunxiao Liu, Chenhao Zhou, Weiya Xia, Yifan Zhou, Yufan Qiu, Jialei Weng, Qiang Zhou, Wanyong Chen, Ying-Nai Wang, Heng-Huan Lee, Shao-Chun Wang, Ming Kuang, Dihua Yu, Ning Ren, Mien-Chie Hung

Faculty, Staff and Student Publications

Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a …

Targeting Prostate Tumor Low-Molecular Weight Tyrosine Phosphatase For Oxidation-Sensitizing Therapy, Stephanie M Stanford, Tiffany P Nguyen, Joseph Chang, Zixuan Zhao, G Lavender Hackman, Eugenio Santelli, Colton M Sanders, Madhusudhanarao Katiki, Eleonora Dondossola, Brooke L Brauer, Michael A Diaz, Yuan Zhan, Sterling H Ramsey, Philip A Watson, Banumathi Sankaran, Claudia Paindelli, Vanessa Parietti, Antonios G Mikos, Alessia Lodi, Aditya Bagrodia, Andrew Elliott, Rana R Mckay, Ramachandran Murali, Stefano Tiziani, Arminja N Kettenbach, Nunzio Bottini

Faculty, Staff and Student Publications

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Kinase-Impaired Btk Mutations Are Susceptible To Clinical-Stage Btk And Ikzf1/3 Degrader Nx-2127, Skye Montoya, Jessie Bourcier, Mark Noviski, Hao Lu, Meghan C Thompson, Alexandra Chirino, Jacob Jahn, Anya K Sondhi, Stefan Gajewski, Ying Siow May Tan, Stephanie Yung, Aleksandra Urban, Eric Wang, Cuijuan Han, Xiaoli Mi, Won Jun Kim, Quinlan Sievers, Paul Auger, Hugo Bousquet, Nivetha Brathaban, Brandon Bravo, Melissa Gessner, Cristiana Guiducci, James N Iuliano, Tim Kane, Ratul Mukerji, Panga Jaipal Reddy, Janine Powers, Mateo Sanchez Garcia De Los Rios, Jordan Ye, Carla Barrientos Risso, Daniel Tsai, Gabriel Pardo, Ryan Q Notti, Alejandro Pardo, Maurizio Affer, Vindhya Nawaratne, Tulasigeri M Totiger, Camila Pena-Velasquez, Joanna M Rhodes, Andrew D Zelenetz, Alvaro Alencar, Lindsey E Roeker, Sanjoy Mehta, Ralph Garippa, Adam Linley, Rajesh Kumar Soni, Sigrid S Skånland, Robert J Brown, Anthony R Mato, Gwenn M Hansen, Omar Abdel-Wahab, Justin Taylor

Faculty, Staff and Student Publications

INTRODUCTION:

Bruton’s tyrosine kinase (BTK) is a nonreceptor kinase in the B cell receptor (BCR) signaling cascade critical for B cell survival. As such, chronic lymphocytic leukemia (CLL) and other B cell cancers are sensitive to inhibition of BTK. Covalent and noncovalent inhibitors of BTK have revolutionized the treatment of these cancers. Therefore, understanding mechanisms by which acquired mutation in BTK confer drug resistance and developing new therapies to overcome resistance are critically important.

RATIONALE:

We recently discovered BTK mutations that confer resistance across covalent and noncovalent BTK inhibitors. In this study, we found that a group of these mutants …

Evaluation Of Ar, Ar-V7, And P160 Family As Biomarkers For Prostate Cancer: Insights Into The Clinical Significance And Disease Progression, Ruan Pimenta, Feres Camargo Malulf, Poliana Romão, Giovana Vilas Boas Caetano, Karina Serafim Da Silva, Vitoria Ghazarian, Gabriel A Dos Santos, Vanessa Guimarães, Iran Amorim Silva, Juliana Alves De Camargo, Saulo Recuero, Bárbara V Lima Aguiar Melão, Alberto Azoubel Antunes, Miguel Srougi, William Nahas, Katia R M Leite, Sabrina T Reis

Faculty, Staff and Student Publications

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression.

METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints.

RESULTS: The AR-V7 diagnostic performance for any …

Tumor-Specific Polycistronic Mirna Delivered By Engineered Exosomes For The Treatment Of Glioblastoma, Malcolm F Mcdonald, Anwar Hossain, Eric N Momin, Irtiza Hasan, Sanjay Singh, Satoshi Adachi, Joy Gumin, Daniel Ledbetter, Jing Yang, Lihong Long, Marc Daou, Sricharan Gopakumar, Lynette M Phillips, Brittany Parker Kerrigan, Frederick F Lang

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) has poor prognosis due to ineffective agents and poor delivery methods. MicroRNAs (miRs) have been explored as novel therapeutics for GBM, but the optimal miRs and the ideal delivery strategy remain unresolved. In this study, we sought to identify the most effective pan-subtype anti-GBM miRs and to develop an improved delivery system for these miRs.

Methods: We conducted an unbiased screen of over 600 miRs against 7 glioma stem cell (GSC) lines representing all GBM subtypes to identify a set of pan-subtype-specific anti-GBM miRs and then used available TCGA GBM patient outcomes and miR expression data to …

Acceptability Of Personalized Lung Cancer Screening Program Among Primary Care Providers, Paul J Resong, Jiangong Niu, Gabrielle F Duhon, Lewis E Foxhall, Sanjay Shete, Robert J Volk, Iakovos Toumazis

Faculty, Staff and Student Publications

Current lung cancer screening (LCS) guidelines rely on age and smoking history. Despite its benefit, only 5%-15% of eligible patients receive LCS. Personalized screening strategies select individuals based on their lung cancer risk and may increase LCS's effectiveness. We assess current LCS practices and the acceptability of personalized LCS among primary care providers (PCP) in Texas. We surveyed 32,983 Texas-based PCPs on an existing network (Protocol 2019-1257; PI: Dr. Shete) and 300 attendees of the 2022 Texas Academy of Family Physicians (TAFP) conference. We analyzed the responses by subgroups of interest. Using nonparametric bootstrap, we derived an enriched dataset to …

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Phenotypic Features Determining Visual Acuity In Albinism And The Role Of Amblyogenic Factors., Frank A Proudlock, Rebecca J Mclean, Viral Sheth, Sarim Ather, Irene Gottlob

Cooper Medical School of Rowan University Departmental Research

Albinism is a spectrum disorder causing foveal hypoplasia, nystagmus, and hypopigmentation of the iris and fundus along with other visual deficits, which can all impact vision. Albinism is also associated with amblyogenic factors which could affect monocular visual acuity. The foveal appearance in albinism can range from mild foveal hypoplasia to that which is indistinguishable from the peripheral retina. The appearance can be quickly and easily graded using the Leicester Grading System in the clinic. However, interquartile ranges of 0.3 logMAR for the grades associated with albinism limit the accuracy of the grading system in predicting vision. Here, we discuss …

Visual Field Deficits In Albinism In Comparison To Idiopathic Infantile Nystagmus., Viral Sheth, Rebecca J Mclean, Zhanhan Tu, Sarim Ather, Irene Gottlob, Frank A Proudlock

Cooper Medical School of Rowan University Departmental Research

PURPOSE: This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA.

METHODS: VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region.

RESULTS: Mean detection thresholds were significantly lower than normative …

Utilizing Primary Human Airway Mucociliary Tissue Cultures To Model Ramifications Of Chronic E-Cigarette Usage., Vincent J Manna, Shannon Dwyer, Vanessa Pizutelli, Salvatore J Caradonna

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Electronic cigarettes are battery powered devices that use a vape-liquid to produce a vapor that is inhaled. A consequence of the rise in e-cigarette usage was the 2019 emergence of a vaping-induced respiratory disease denoted as 'e-cigarette or vaping use-associated lung injury' (EVALI). One of the suspected causes of EVALI is Vitamin E Acetate (VEA), which was found to be a diluent in certain illicit vape-pens, whereas nicotine is commonly diluted in equal parts propylene glycol and vegetable glycerin (PG:VG). The prevalent use of e-cigarettes and the emergence of a novel illness has made understanding how e-cigarette vapors affect our …

Veterans Health Administration Enrollees’ Choice Of Care Setting Relates To The Expansion Of Care Options: Evidence From Screening Colonoscopies Before And After The Mission Act, Chase S Eck, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To estimate whether those enrolled in the Veterans Health Administration (VHA) were less likely to use VHA-delivered colorectal cancer screening colonoscopies after the MISSION Act.

Data sources and study setting: Secondary data were collected on VHA-enrolled Veterans from FY2017-FY2021.

Study design: This retrospective cross-sectional study measured the volume and share of screening colonoscopies that were VHA-delivered over time and by drive time eligibility-defined as living more than 60 min away from the nearest VHA specialty-care clinic. We used a multivariable logistic regression to adjust for patient and facility factors.

Data extraction: Data were extracted for VHA enrollees (n = …

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Biallelic Creld1 Variants Cause A Multisystem Syndrome, Including Neurodevelopmental Phenotypes, Cardiac Dysrhythmias, And Frequent Infections, Lauren Jeffries, Emily K Mis, Kirsty Mcwalter, Sandra Donkervoort, Nina N Brodsky, Jean-Marie Carpier, Weizhen Ji, Cristian Ionita, Bhaskar Roy, Jon S Morrow, Armine Darbinyan, Krishna Iyer, Ritu B Aul, Siddharth Banka, Katherine R Chao, Laura Cobbold, Stacey Cohen, Helena M Custodio, Margaret Drummond-Borg, Frances Elmslie, Erika Finanger, Bryan E Hainline, Ingo Helbig, Stacy Hewson, Ying Hu, Adam Jackson, Dragana Josifova, Monica Konstantino, Meganne E Leach, Bryan Mak, David Mccormick, Elisabeth Mcgee, Stanley Nelson, Joanne Nguyen, Kimberly Nugent, Lucy Ortega, Howard P Goodkin, Elizabeth Roeder, Sani Roy, Katie Sapp, Dimah Saade, Sanjay M Sisodiya, Karen Stals, Shelley Towner, William Wilson, Deciphering Developmental Disorders, Genomics England Research Consortium, Undiagnosed Disease Network, Mustafa K Khokha, Carsten G Bönnemann, Carrie L Lucas, Saquib A Lakhani

Faculty, Staff and Students Publications

PURPOSE: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

METHODS: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

RESULTS: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense …

Proximity Extension Assay Proteomics And Renal Single Cell Transcriptomics Uncover Novel Urinary Biomarkers For Active Lupus Nephritis, Yaxi Li, Chenling Tang, Kamala Vanarsa, Nga Thai, Jessica Castillo, Gabrielle Alexis Braza Lea, Kyung Hyun Lee, Soojin Kim, Claudia Pedroza, Tianfu Wu, Ramesh Saxena, Chi Chiu Mok, Chandra Mohan

Faculty, Staff and Student Publications

Objective: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE).

Methods: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers.

Results: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously …

Unanswered Questions Following Reports Of Secondary Malignancies After Car-T Cell Therapy, Bruce L Levine, Marcelo C Pasquini, John E Connolly, David L Porter, Michael P Gustafson, Jaap J Boelens, Edwin M Horwitz, Stephan A Grupp, Marcela V Maus, Frederick L Locke, Fabio Ciceri, Annalisa Ruggeri, John Snowden, Helen E Heslop, Crystal L Mackall, Carl H June, Anna M Sureda, Miguel-Angel Perales

Faculty, Staff and Students Publications

Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Endothelial Cells Adopt A Pro-Reparative Immune Responsive Signature During Cardiac Injury, Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

Faculty, Staff and Students Publications

Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors …

Improving Veteran Engagement With Virtual Care Technologies: A Veterans Health Administration State Of The Art Conference Research Agenda, Taona P Haderlein, Jenice Guzman-Clark, Navid S Dardashti, Nicholas Mcmahon, Elizabeth L Duran, Jolie N Haun, Stephanie A Robinson, Amanda C Blok, Sarah L Cutrona, Jan A Lindsay, Christina M Armstrong, Kim M Nazi, Stephanie L Shimada, Nancy R Wilck, Erin Reilly, Eric Kuhn, Timothy P Hogan

Faculty, Staff and Students Publications

Although the availability of virtual care technologies in the Veterans Health Administration (VHA) continues to expand, ensuring engagement with these technologies among Veterans remains a challenge. VHA Health Services Research & Development convened a Virtual Care State of The Art (SOTA) conference in May 2022 to create a research agenda for improving virtual care access, engagement, and outcomes. This article reports findings from the Virtual Care SOTA engagement workgroup, which comprised fourteen VHA subject matter experts representing VHA clinical care, research, administration, and operations. Workgroup members reviewed current evidence on factors and strategies that may affect Veteran engagement with virtual …

Development And Validation Of A Risk Model For Hospital-Acquired Venous Thrombosis: The Medical Inpatients Thrombosis And Hemostasis Study, Neil A Zakai, Katherine Wilkinson, Andrew D Sparks, Ryan T Packer, Insu Koh, Nicholas S Roetker, Allen B Repp, Ryan Thomas, Chris E Holmes, Mary Cushman, Timothy B Plante, Hanny Al-Samkari, Allyson M Pishko, William A Wood, Camila Masias, Radhika Gangaraju, Ang Li, David Garcia, Kerri L Wiggins, Jordan K Schaefer, Craig Hooper, Nicholas L Smith, Leslie A Mcclure

Faculty, Staff and Students Publications

Background: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients.

Objectives: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission.

Methods: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged < 18 years, and admitted for < 1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM.

Results: The development cohort included …

Herpes Zoster And Risk Of Incident Parkinson's Disease In Us Veterans: A Matched Cohort Study, Louis Tunnicliffe, Rimona S Weil, Judith Breuer, Maria C Rodriguez-Barradas, Liam Smeeth, Christopher T Rentsch, Charlotte Warren-Gash

Faculty, Staff and Students Publications

Background: Although some systemic infections are associated with Parkinson's disease (PD), the relationship between herpes zoster (HZ) and PD is unclear.

Objective: The objective is to investigate whether HZ is associated with incident PD risk in a matched cohort study using data from the US Department of Veterans Affairs.

Methods: We compared the risk of PD between individuals with incident HZ matched to up to five individuals without a history of HZ using Cox proportional hazards regression. In sensitivity analyses, we excluded early outcomes.

Results: Among 198,099 individuals with HZ and 976,660 matched individuals without HZ (median age 67.0 years …

Stabilizing The Proteomes Of Acute Myeloid Leukemia Cells: Implications For Cancer Proteomics, Robert W Sprung, Qiang Zhang, Michael H Kramer, Matthew C Christopher, Petra Erdmann-Gilmore, Yiling Mi, James P Malone, Timothy J Ley, R Reid Townsend

2020-Current year OA Pubs

Previous work has shown that inhibition of abundant myeloid azurophil granule-associated serine proteases (ELANE [neutrophil elastase], PRTN3 [protease 3], and CTSG [Cathepsin G]) is required to stabilize some proteins in myeloid cells. We therefore hypothesized that effective inhibition of these proteases may be necessary for quantitative proteomic analysis of samples containing myeloid cells. To test this hypothesis, we thawed viably preserved acute myeloid leukemia cells from cryovials in the presence or the absence of diisopropyl fluorophosphate (DFP), a cell-permeable and irreversible serine protease inhibitor. Global proteomic analysis was performed, using label-free and isobaric peptide-labeling quantitation. The presence of DFP resulted …

"We Need A Little Strength As Well": Examining The Social Context Of Informal Caregivers For Black Women With Breast Cancer, Tess Thompson, Jacquelyn Coats, Merriah Croston, Robert O Motley Jr, Vetta Sanders Thompson, Aimee S James, Lashaune P Johnson

2020-Current year OA Pubs

BACKGROUND: Informal caregivers (e.g., partners, other family members, friends) often provide social support to Black women with breast cancer, and caregivers find both benefits and challenges in their caregiving role.

METHODS: In this qualitative study, twenty-four caregivers for Black women with breast cancer participated in focus groups and interviews. Participants responded to a brief close-ended questionnaire as well as semi-structured questions about their experiences as cancer caregivers. Demographic information was collected, and relationship satisfaction was measured by the Relationship Assessment Scale-General scale (RAS-G). Focus groups and interviews were recorded, transcribed verbatim, and coded by two independent coders. Using an iterative, …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Influences Of Specialty Identity When Implementing A New Emergency Department In Denmark: A Qualitative Study, Jeanette Wassar Kirk, Mette Bendtz Lindstroem, Nina Thórný Stefánsdóttir, Ove Andersen, Byron J Powell, Per Nilsen, Tine Tjørnhøj-Thomsen

2020-Current year OA Pubs

BACKGROUND: The Danish Health Authority recommended the implementation of new types of emergency departments. Organizational changes in the hospital sector challenged the role, identity, and autonomy of medical specialists. They tend to identify with their specialty, which can challenge successful implementation of change. However, investigations on specialty identity are rare in implementation science, and how the co-existence of different specialty identities influences the implementation of new emergency departments needs to be explored for the development of tailored implementation strategies. The aim of this study was to examine how medical specialty identity influences collaboration between physicians when implementing a new emergency …

A Deep Learning Approach To Remove Contrast From Contrast-Enhanced Ct For Proton Dose Calculation, Xu Wang, Yao Hao, Ye Duan, Deshan Yang

2020-Current year OA Pubs

PURPOSE: Non-Contrast Enhanced CT (NCECT) is normally required for proton dose calculation while Contrast Enhanced CT (CECT) is often scanned for tumor and organ delineation. Possible tissue motion between these two CTs raises dosimetry uncertainties, especially for moving tumors in the thorax and abdomen. Here we report a deep-learning approach to generate NCECT directly from CECT. This method could be useful to avoid the NCECT scan, reduce CT simulation time and imaging dose, and decrease the uncertainties caused by tissue motion between otherwise two different CT scans.

METHODS: A deep network was developed to convert CECT to NCECT. The network …

Racial Differences In Treatment And Survival Among Older Patients With Multiple Myeloma, Rong Wang, Natalia Neparidze, Xiaomei Ma, Graham A Colditz, Su-Hsin Chang, Shi-Yi Wang

2020-Current year OA Pubs

BACKGROUND: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients are well-established, it is unclear whether they have persisted after the introduction of novel agents.

METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between …