Diseases Commons^™

Downregulated Klf2 In Polycythemia Vera And Essential Thrombocythemia Induces Prothrombotic Gene Expression, Jihyun Song, Soo Jin Kim, Jahnavi Gollamudi, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thromboses are major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) diseases associated with JAK2V617F mutation. However, the molecular mechanism(s) of increased thrombosis in PV and ET remain unknown. Kruppel-like factor 2 (KLF2) is a transcription factor that regulates expression of genes associated with inflammation and thrombosis; the absence of KLF2 in neutrophils causes thrombosis by inducing tissue factor. We studied the role of KLF2 in regulating prothrombotic gene expression in PV and ET. Neutrophils and platelets KLF2 expression in PV and ET was lower than the controls. Furthermore, in patients with thromboses, KLF2 transcripts …

Varied Performance Of Picture Description Task As A Screening Tool Across Mci Subtypes, Joan A. Mefford, Zilong Zhao, Leah Heilier, Man Xu, Guifeng Zhou, Rachel Mace, Kelly L. Sloane, Shannon M. Sheppard, Shenly Glenn

Communication Sciences and Disorders Faculty Articles and Research

A picture description task is a component of Miro Health’s platform for self-administration of neurobehavioral assessments. Picture description has been used as a screening tool for identification of individuals with Alzheimer’s disease and mild cognitive impairment (MCI), but currently requires in-person administration and scoring by someone with access to and familiarity with a scoring rubric. The Miro Health implementation allows broader use of this assessment through self-administration and automated processing, analysis, and scoring to deliver clinically useful quantifications of the users’ speech production, vocal characteristics, and language. Picture description responses were collected from 62 healthy controls (HC), and 33 participants …

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert

School of Medicine Faculty Publications

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …

Structure-Based Regulatory Role For The 5'Utr Of Rcnmv Rna2, Jennifer S H Im, Jasmine R Sheppard, K Andrew White

Faculty, Staff and Student Publications

Red clover necrotic mosaic virus (RCNMV) is a segmented positive-strand RNA virus consisting of RNA1 and RNA2. Previous studies demonstrated that efficient translation of RCNMV RNA2 requires de novo synthesis of RNA2 during infections, suggesting that RNA2 replication is required for its translation. We explored a potential mechanism underlying the regulation of replication-associated translation of RNA2 by examining RNA elements in its 5' untranslated region (5'UTR). Structural analysis of the 5'UTR suggested that it can form two mutually exclusive configurations: a more thermodynamically stable conformation, termed the 5'-basal stem structure (5'BS), in which 5'-terminal sequences are base paired, and an …

Towards A Biomarker For Acute Arterial Thrombosis Using Complete Blood Count And White Blood Cell Differential Parameters In Mice, Hee Jeong Jang, Dawid Schellingerhout, Jiwon Kim, Jinyong Chung, Dong-Eog Kim

Faculty, Staff and Student Publications

There is no blood biomarker diagnostic of arterial thrombosis. We investigated if arterial thrombosis per se was associated with alterations in complete blood count (CBC) and white blood cell (WBC) differential count in mice. Twelve-week-old C57Bl/6 mice were used for FeCl3-mediated carotid thrombosis (n = 72), sham-operation (n = 79), or non-operation (n = 26). Monocyte count (/µL) at 30-min after thrombosis (median 160 [interquartile range 140-280]) was ~ 1.3-fold higher than at 30-min after sham-operation (120 [77.5-170]), and twofold higher than in non-operated mice (80 [47.5-92.5]). At day-1 and -4 post-thrombosis, compared with 30-min, monocyte count decreased by about …

Interactions Of Snps In Folate Metabolism Related Genes On Prostate Cancer Aggressiveness In European Americans And African Americans, Hui Yi Lin, Susan E. Steck, Indrani Sarkar, Elizabeth T.H. Fontham, Alan Diekman, Lora J. Rogers, Calvin T. Ratliff, Jeannette T. Bensen, James L. Mohler, L. Joseph Su

School of Public Health Faculty Publications

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP …

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …

Pragmatic, Prospective Comparative Effectiveness Trial Of Carbon Ion Therapy, Surgery, And Proton Therapy For The Management Of Pelvic Sarcomas (Soft Tissue/Bone) Involving The Bone: The Prosper Study Rationale And Design, Bradford S Hoppe, Ivy A Petersen, Benjamin K Wilke, Todd A Dewees, Reiko Imai, Eugen B Hug, Maria Rosaria Fiore, Jürgen Debus, Piero Fossati, Shigeru Yamada, Ester Orlandi, Qing Zhang, Cihang Bao, Katharina Seidensaal, Byron C May, Anna C Harrell, Matthew T Houdek, Laura A Vallow, Peter S Rose, Michael G Haddock, Jonathan B Ashman, Krista A Goulding, Steven Attia, Sunil Krishnan, Anita Mahajan, Robert L Foote, Nadia N Laack, Sameer R Keole, Chris J Beltran, Eric M Welch, Mohammed Karim, Safia K Ahmed

Faculty, Staff and Student Publications

Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic …

Multifaceted Role For P53 In Pancreatic Cancer Suppression, Stephano S Mello, Brittany M Flowers, Pawel K Mazur, James J Lee, Fabian Müller, Sarah K Denny, Sofia Ferreira, Kathryn Hanson, Seung K Kim, William J Greenleaf, Laura D Wood, Laura D Attardi

Faculty, Staff and Student Publications

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC. However, the cellular basis for p53 action during PDAC development has not been explored in detail. Here, we leverage a hyperactive p53 variant-p5353,54-which we previously showed is a more robust PDAC suppressor than …

A Comprehensive And Integrative Approach To Mecp2 Disease Transcriptomics, Alexander J Trostle, Lucian Li, Seon-Young Kim, Jiasheng Wang, Rami Al-Ouran, Hari Krishna Yalamanchili, Zhandong Liu, Ying-Wooi Wan

Faculty, Staff and Students Publications

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2's molecular role. Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonstrate a methodology to analyze all modern public data. We obtained relevant raw public transcriptomic data from GEO and ENA, then homogeneously processed it (QC, alignment to reference, differential expression analysis). We present a web portal to interactively access the mouse data, and we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found functionally distinct, consistently up- and …

Clinically Adjudicated Reference Standards For Evaluation Of Infectious Diseases Diagnostics, Robin Patel, Ephraim L Tsalik, Scott Evans, Vance G Fowler, Sarah B Doernberg, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Lack of a gold standard can present a challenge for evaluation of diagnostic test accuracy of some infectious diseases tests, particularly when the test's accuracy potentially exceeds that of its predecessors. This approach may measure agreement with an imperfect reference, rather than correctness, because the right answer is unknown. Solutions consist of multitest comparators, including those that involve a test under evaluation if multiple new tests are being evaluated together, using latent class modeling, and clinically adjudicated reference standards. Clinically adjudicated reference standards may be considered as comparator methods when no predefined test or composite of tests is sufficiently accurate; …

The Ipdgc/Gp2 Hackathon - An Open Science Event For Training In Data Science, Genomics, And Collaboration Using Parkinson's Disease Data, Hampton L Leonard, Ruqaya Murtadha, Alejandro Martinez-Carrasco, Alina Jama, Amica Corda Müller-Nedebock, Ana-Luisa Gil-Martinez, Anastasia Illarionova, Anni Moore, Bernabe I Bustos, Bharati Jadhav, Brook Huxford, Catherine Storm, Clodagh Towns, Dan Vitale, Devina Chetty, Eric Yu, Francis P Grenn, Gabriela Salazar, Geoffrey Rateau, Hirotaka Iwaki, Inas Elsayed, Isabelle Francesca Foote, Zuné Jansen Van Rensburg, Jonggeol Jeff Kim, Jie Yuan, Julie Lake, Kajsa Brolin, Konstantin Senkevich, Lesley Wu, Manuela M X Tan, María Teresa Periñán, Mary B Makarious, Michael Ta, Nikita Simone Pillay, Oswaldo Lorenzo Betancor, Paula R Reyes-Pérez, Pilar Alvarez Jerez, Prabhjyot Saini, Rami Al-Ouran, Ramiya Sivakumar, Raquel Real, Regina H Reynolds, Ruifneg Hu, Shameemah Abrahams, Shilpa C Rao, Tarek Antar, Thiago Peixoto Leal, Vassilena Iankova, William J Scotton, Yeajin Song, Andrew Singleton, Mike A Nalls, Sumit Dey, Sara Bandres-Ciga, Cornelis Blauwendraat, Alastair J Noyce, The International Parkinson Disease Genomics Consortium (Ipdgc) And The Global Parkinson’S Genetics Program (Gp2)

Faculty, Staff and Students Publications

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of …

Results Of Duet: A Web-Based Weight Loss Randomized Controlled Feasibility Trial Among Cancer Survivors And Their Chosen Partners, Wendy Demark-Wahnefried, Robert A Oster, Tracy E Crane, Laura Q Rogers, W Walker Cole, Harleen Kaur, David Farrell, Kelsey B Parrish, Hoda J Badr, Kathleen Y Wolin, Dori W Pekmezi

Faculty, Staff and Students Publications

Simple Summary

Effective and scalable diet, exercise, and weight management interventions are needed for primary cancer prevention in the general public, as well as for cancer control and tertiary prevention among the growing population of cancer survivors. A 6-month online intervention, entitled “Daughters, dUdes, mothErs, and others Together” (DUET), was designed to promote weight loss, a healthful diet, and increased physical activity among cancer survivors and their chosen partners. Fifty-six cancer survivor-partner dyads (n = 112 participants in total) were recruited into a randomized controlled trial that compared DUET to a waitlist control. The trial surpassed all feasibility endpoints …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Taking A Load Off: User Perceptions Of Smart Offloading Walkers For Diabetic Foot Ulcers Using The Technology Acceptance Model, M G Finco, Gozde Cay, Myeounggon Lee, Jason Garcia, Elia Salazar, Tze-Woei Tan, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

People with diabetic foot ulcers (DFUs) are commonly prescribed offloading walkers, but inadequate adherence to prescribed use can be a barrier to ulcer healing. This study examined user perspectives of offloading walkers to provide insight on ways to help promote adherence. Participants were randomized to wear: (1) irremovable, (2) removable, or (3) smart removable walkers (smart boot) that provided feedback on adherence and daily walking. Participants completed a 15-item questionnaire based on the Technology Acceptance Model (TAM). Spearman correlations assessed associations between TAM ratings with participant characteristics. Chi-squared tests compared TAM ratings between ethnicities, as well as 12-month retrospective fall …

Association Of Qaca/B And Smr Carriage With Staphylococcus Aureus Survival Following Exposure To Antiseptics In An Ex Vivo Venous Catheter Disinfection Model, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Many health care centers have reported an association between Staphylococcus aureus isolates bearing efflux pump genes and an elevated MIC/minimal bactericidal concentration (MBC) to chlorhexidine gluconate (CHG) and other antiseptics. The significance of these organisms is uncertain, given that their MIC/MBC is typically far lower than the CHG concentration in most commercial preparations. We sought to evaluate the relationship between carriage of the efflux pump genes qacA/B and smr in S. aureus and the efficacy of CHG-based antisepsis in a venous catheter disinfection model. S. aureus isolates with and without smr and/or qacA/B were utilized. The CHG MICs were determined. …

Macrophage-Derived Mlkl In Alcohol-Associated Liver Disease: Regulation Of Phagocytosis, Xiaoqin Wu, Xiude Fan, Megan R Mcmullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z Day, Josiah E Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S Allende, Arthur J Mccullough, Jon M Jacobs, Daniel M Rotroff, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury.

APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced …

Mew Network Self-Management Program Characteristics And Lessons Learned Through The Re-Aim Framework, Cam Escoffery, Archna Patel, Jerik Leung, Molly Anderson, Robin Mcgee, Martha Sajatovic, Erica K Johnson, Barbara Jobst, Elaine T Kiriakopoulos, Ross Shegog, Robert Fraser, Rakale C Quarells

Faculty, Staff and Student Publications

RATIONALE: The promotion of evidence-based self-management support for people living with chronic conditions such as epilepsy is a public health priority. Epilepsy self-management encompasses three general areas: (1) treatment management, (2) seizure management, and (3) lifestyle management. Interventions focusing on self-management have increased quality of life and adherence to treatment. This study assesses and synthesizes the Managing Epilepsy Well Network (MEWN) program implementation experiences using the RE-AIM framework. This research informs the quality and rigor of MEWN program dissemination and implementation efforts to assess whether these programs are being implemented and their scalability.

METHODS: The study data were derived from …

Global Epidemiology And Clinical Outcomes Of Carbapenem-Resistant Pseudomonas Aeruginosa And Associated Carbapenemases (Pop): A Prospective Cohort Study, Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake M Hanson, Eric Cober, Erica Herc, Thamer Alenazi, Keith S Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha S Kanj, Zhengyin Liu, Jose M Oñate, Robert A Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra L Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian M Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin E Stryjewski, Jose M Munita, David L Paterson, Scott Evans, Carol Hill, Keri Baum, Robert A Bonomo, Barry N Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, Yohei Doi, David Van Duin, Michael J Satlin

Faculty, Staff and Student Publications

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.

Methods: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day …

Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth And Metabolic Reprogramming Leading To Chemoresistance, Sumeet Solanki, Katherine Sanchez, Varun Ponnusamy, Vasudha Kota, Hannah N Bell, Chun-Seok Cho, Allison H Kowalsky, Michael Green, Jun Hee Lee, Yatrik M Shah

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear.

METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic …

Immunocompromised Host Pneumonia: Definitions And Diagnostic Criteria: An Official American Thoracic Society Workshop Report, Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Jason W Chien, Catia Cilloniz, Keira Cohen, Nathan Dean, Charles S Dela Cruz, Robert P Dickson, Alexander L Greninger, Chadi A Hage, Tobias M Hohl, Steven M Holland, Barbara E Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos I Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L Winthrop, Richard G Wunderink, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …

Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation, Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed …

Deep Learning-Based Pathology Image Analysis Predicts Cancer Progression Risk In Patients With Oral Leukoplakia, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Roberta Rayra Martins-Chaves, Ricardo Santiago Gomez, Nadarajah Vigneswaran, Arunangshu Sarkar, William N William, Vassiliki Papadimitrakopoulou, Michelle Williams, Diana Bell, Doreen Palsgrove, Justin Bishop, John V Heymach, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Scott M Lippman, Curtis Rg Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models.

METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could …

Longitudinal Changes In Fibrosis Markers Are Associated With Risk Of Cirrhosis And Hepatocellular Carcinoma In Non-Alcoholic Fatty Liver Disease, George Cholankeril, Jennifer R Kramer, Jinna Chu, Xian Yu, Maya Balakrishnan, Liang Li, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD.

METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced …

Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa

Faculty, Staff and Students Publications

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed.

MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics …

Bacteremia Due To Non-Staphylococcus Aureus Gram-Positive Cocci And Risk Of Cardiovascular Implantable Electronic Device Infection, Supavit Chesdachai, Larry M Baddour, M Rizwan Sohail, Bharath Raj Palraj, Malini Madhavan, Hussam Tabaja, Madiha Fida, Brian D Lahr, Daniel C Desimone

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular implantable electronic device (CIED) infection carries significant morbidity and mortality with bacteremia being a possible marker of device infection. A clinical profile of non-Staphylococcus aureus gram-positive cocci (non-SA GPC) bacteremia in patients with CIED has been limited.

OBJECTIVE: To examine characteristics of patients with CIED who developed non-SA GPC bacteremia and risk of CIED infection.

METHODS: We reviewed all patients with CIED who developed non-SA GPC bacteremia at the Mayo Clinic between 2012 and 2019. The 2019 European Heart Rhythm Association Consensus Document was used to define CIED infection.

RESULTS: A total of 160 patients with CIED …

Association Of Long-Term Change In N-Terminal Pro-B-Type Natriuretic Peptide With Incident Heart Failure And Death, Xiaoming Jia, Mahmoud Al Rifai, Ron Hoogeveen, Justin B Echouffo-Tcheugui, Amil M Shah, Chiadi E Ndumele, Salim S Virani, Biykem Bozkurt, Elizabeth Selvin, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

IMPORTANCE: Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events.

OBJECTIVE: To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death.

DESIGN, SETTING, AND PARTICIPANTS: Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and …

Turmeric-Associated Liver Injury: A Rare Case Of Drug-Induced Liver Injury, David N Smith, Prisca Pungwe, Lauren L Comer, Teminioluwa A Ajayi, Milena G Suarez

Faculty, Staff and Students Publications

Turmeric is popularly used as a naturopathic supplement associated with myriad benefits and has long been generally regarded as safe. However, increasing reports of turmeric-associated liver injury have emerged over recent years. This case presents a female patient without significant past medical history who presents with signs and symptoms of acute hepatitis after consuming a turmeric-containing tea. Her case adds to a growing body of evidence that dosage safety, manufacturing, and pharmacologic delivery practices for turmeric supplements should be investigated.

Driving Impairment In Movement Disorders, Karim Makhoul, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Driving may be adversely affected by any movement disorder, but has been mostly studied in Parkinson's disease (PD). Few studies have addressed driving impairment in patients with Huntington's disease (HD); driving in other movement disorders such as dystonia, blepharospasm and Tourette syndrome (TS) has not been adequately evaluated.

OBJECTIVES: The aim of this review is to summarize the findings of driving impairment in movement disorders and evaluate the usefulness of clinical tools in guiding clinicians whether to refer patients for driving assessment.

METHODS: A review of literature was performed on PubMed and articles on driving and movement disorders were …