Medical Specialties Commons^™

Performance Of A Sars-Cov-2 Rt-Pcr Assay With Non-Traditional Specimen Types, Subathra Marimuthu, Holly Aliesky, Heather Ness, Daniya Sheikh, Sathya Rashmit, Dawn Balcom, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used …

Disruption Of The Atxn1-Cic Complex Reveals The Role Of Additional Nuclear Atxn1 Interactors In Spinocerebellar Ataxia Type 1, Stephanie L Coffin, Mark A Durham, Larissa Nitschke, Eder Xhako, Amanda M Brown, Jean-Pierre Revelli, Esmeralda Villavicencio Gonzalez, Tao Lin, Hillary P Handler, Yanwan Dai, Alexander J Trostle, Ying-Wooi Wan, Zhandong Liu, Roy V Sillitoe, Harry T Orr, Huda Y Zoghbi

Faculty, Staff and Students Publications

Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative disease in that it is caused by a mutation in a broadly expressed protein, ATXN1; however, only select populations of cells degenerate. The interaction of polyglutamine-expanded ATXN1 with the transcriptional repressor CIC drives cerebellar Purkinje cell pathogenesis; however, the importance of this interaction in other vulnerable cells remains unknown. Here, we mutated the 154Q knockin allele of Atxn1154Q/2Q mice to prevent the ATXN1-CIC interaction globally. This normalized genome-wide CIC binding; however, it only partially corrected transcriptional and behavioral phenotypes, suggesting the involvement of additional factors in disease pathogenesis. Using unbiased …

Mortality And Major Adverse Cardiovascular Events In Hospitalized Patients With Atrial Fibrillation With Covid-19, Lucas Wang, Lawrence Hoang, Kristopher Aten, Mujahed Abualfoul, Victor Canela, Sri Prathivada, Michael Vu, Yi Zhao, Manavjot Sidhu

Faculty, Staff and Student Publications

COVID-19 results in increased incidence of cardiac arrhythmias, including atrial fibrillation (AF). However, little is known about the combined effect of AF and COVID-19 on patient outcomes. This study aimed to determine if AF, specifically new-onset AF (NOAF), is associated with increased risk of mortality and major adverse cardiovascular events (MACEs) in hospitalized patients with COVID-19. This multicenter retrospective analysis identified 2,732 patients with COVID-19 admitted between March and December 2020. Data points were manually reviewed in the patients' electronic health records. Multivariate logistic regression was used to assess if AF was associated with death or MACE. Patients with AF …

Itch And Janus Kinase Inhibitors, Yujin Han, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Faculty, Staff and Student Publications

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for …

Hemoglobinopathy Is Associated With Total Hip Arthroplasty Indication Even Beyond Sickle Cell Anemia, Maxwell J. Rakutt, Daniel N. Bracey, Anna Cohen-Rosenblum, Peter K. Sculco, Franco M. Sabatini, Cale A. Jacobs, Stephen T. Duncan, David C. Landy

School of Medicine Faculty Publications

Background: The extent to which hemoglobinopathies other than sickle anemia (HbSS) are associated with hip osteonecrosis is unknown. Sickle cell trait (HbS), hemoglobin SC (HbSC), and sickle/β-thalassemia (HbSβTh) may also predispose to osteonecrosis of the femoral head (ONFH). We sought to compare the distributions of indications for a total hip arthroplasty (THA) in patients with and without specific hemoglobinopathies. Methods: PearlDiver, an administrative claims database, was used to identify 384,401 patients aged 18 years or older undergoing a THA not for fracture from 2010 to 2020, with patients grouped by diagnosis code (HbSS N = 210, HbSC N = 196, …

Single-Cell Sequencing Of Ascites Fluid Illustrates Heterogeneity And Therapy-Induced Evolution During Gastric Cancer Peritoneal Metastasis, Xuan-Zhang Huang, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Jing-Xu Sun, Yong-Xi Song, Hong-Jie Ni, Shi-Yu Ye, Shi Bai, Teng-Hui Li, Xin-Yu Wang, Jing-Yuan Lu, Jin-Jia Yang, Xun Sun, Jason C Mills, Zhi-Feng Miao, Zhen-Ning Wang

Faculty, Staff and Students Publications

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a …

Optimizing Dna Extraction From Pediatric Stool For Diagnosis Of Tuberculosis And Use In Next-Generation Sequencing Applications, Tara E Ness, Lennard Meiwes, Alexander Kay, Rojelio Mejia, Christoph Lange, Maha Farhat, Anna Mandalakas, Andrew Dinardo

Faculty, Staff and Students Publications

The WHO has endorsed the use of stool samples for diagnosis of tuberculosis (TB) in children, and targeted next-generation sequencing (tNGS) of stool has been shown to support diagnosis and provide information about drug susceptibility (DS). Optimizing extraction of DNA from stool for sequencing is critical to ensure high diagnostic sensitivity and accurate DS information. Human stool samples were spiked with various concentrations of Mycobacterium bovis bacillus Calmette-Guérin (BCG), and DNA was extracted from the samples using four different DNA extraction kits. Each sample was subjected to quantitative PCR for identifying Mycobacterium tuberculosis complex bacteria and underwent further analysis to …

What? Now A Respiratory Syncytial Virus Epidemic, Aya Allam, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Endovascular Vs Medical Management For Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis Of Clear And Rescue-Japan, James E Siegler, Muhammad M Qureshi, Raul G Nogueira, Kanta Tanaka, Simon Nagel, Patrik Michel, Nicholas Vigilante, Marc Ribo, Hiroshi Yamagami, Shinichi Yoshimura, Mohamad Abdalkader, Diogo C Haussen, Mahmoud H Mohammaden, Stefania Nannoni, Markus A Möhlenbruch, Hilde Henon, Sunil A Sheth, Santiago Ortega-Gutierrez, Marta Olive-Gadea, Francois Caparros, Fatih Seker, Syed Zaidi, Alicia C Castonguay, Kazutaka Uchida, Nobuyuki Sakai, Ajit S Puri, Mudassir Farooqui, Kazunori Toyoda, Sergio Salazar-Marioni, Masataka Takeuchi, Behzad Farzin, Hesham E Masoud, Anna Luisa Kuhn, Ameena Rana, Masafumi Morimoto, Masunari Shibata, Tadashi Nonaka, Piers Klein, Anvitha Sathya, Nicole L Kiley, Charlotte Cordonnier, Davide Strambo, Jelle Demeestere, Peter A Ringleb, Daniel Roy, Osama O Zaidat, Tudor G Jovin, Johannes Kaesmacher, Urs Fischer, Jean Raymond, Thanh N Nguyen

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO.

METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from …

Response Assessment In Pediatric Craniopharyngioma: Recommendations From The Response Assessment In Pediatric Neuro-Oncology (Rapno) Working Group, Lindsey M Hoffman, Camilo Jaimes, Kshitij Mankad, David M Mirsky, Benita Tamrazi, Christopher L Tinkle, Cassie Kline, Aparna Ramasubramanian, Fatema Malbari, Ross Mangum, Holly Lindsay, Vincent Horne, David J Daniels, Sameer Keole, David R Grosshans, Tina Young Poussaint, Roger Packer, Sergio Cavalheiro, Brigitte Bison, Todd C Hankinson, Hermann L Müller, Ute Bartels, Katherine E Warren, Murali Chintagumpala

Faculty, Staff and Student Publications

BACKGROUND: Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized.

METHODS: The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively.

RESULTS: Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor …

Survival Improvement For Patients With Metastatic Colorectal Cancer Over Twenty Years, Fadl A Zeineddine, Mohammad A Zeineddine, Abdelrahman Yousef, Yue Gu, Saikat Chowdhury, Arvind Dasari, Ryan W Huey, Benny Johnson, Bryan Kee, Michael S Lee, Maria Pia Morelli, Van K Morris, Michael J Overman, Christine Parseghian, Kanwal Raghav, Jason Willis, Robert A Wolff, Yoshikuni Kawaguchi, Jean-Nicolas Vauthey, Ryan Sun, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed …

N-Of-1 Trials Vs Usual Care In Children With Hypertension: A Pilot Randomized Clinical Trial, Joyce P Samuel, Cynthia S Bell, Joshua A Samuels, Celin Rajan, Adrienne K Walton, Charles Green, Jon E Tyson

Faculty, Staff and Student Publications

BACKGROUND: Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care.

METHODS: A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10-22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary …

Adapting International Clinical Trials During Covid-19 And Beyond, Kamala Thriemer, Kamala Thriemer, Mohammad Shafiul Alam, Bipin Adhikari, Rupam Tripura, Mohammad Sharif Hossain, Michael Christian, Najia Bano Ghanchi, Hellen Mnjala, Muhammad Asim

Department of Pathology and Laboratory Medicine

Background: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration.
The new working model: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for …

Transfusing Convalescent Plasma As Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial, Shmuel Shoham, Evan M Bloch, Arturo Casadevall, Daniel Hanley, Bryan Lau, Kelly Gebo, Edward Cachay, Seble G Kassaye, James H Paxton, Jonathan Gerber, Adam C Levine, Arash Naeim, Judith Currier, Bela Patel, Elizabeth S Allen, Shweta Anjan, Lawrence Appel, Sheriza Baksh, Paul W Blair, Anthony Bowen, Patrick Broderick, Christopher A Caputo, Valerie Cluzet, Marie Elena Cordisco, Daniel Cruser, Stephan Ehrhardt, Donald Forthal, Yuriko Fukuta, Amy L Gawad, Thomas Gniadek, Jean Hammel, Moises A Huaman, Douglas A Jabs, Anne Jedlicka, Nicky Karlen, Sabra Klein, Oliver Laeyendecker, Karen Lane, Nichol Mcbee, Barry Meisenberg, Christian Merlo, Giselle Mosnaim, Han-Sol Park, Andrew Pekosz, Joann Petrini, William Rausch, David M Shade, Janna R Shapiro, J Robinson Singleton, Catherine Sutcliffe, David L Thomas, Anusha Yarava, Martin Zand, Jonathan M Zenilman, Aaron A R Tobian, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was …

Hepatocytes Demarcated By Ephb2 Contribute To The Progression Of Nonalcoholic Steatohepatitis, Yang Xiao, Kirill Batmanov, Wenxiang Hu, Kun Zhu, Alexander Y Tom, Dongyin Guan, Chunjie Jiang, Lan Cheng, Sam J Mccright, Eric C Yang, Matthew R Lanza, Yifan Liu, David A Hill, Mitchell A Lazar

Faculty, Staff and Students Publications

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor …

Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Testing And Detection During Peripartum Hospitalizations Among A Multicenter Cohort Of Pregnant Persons: March 2020-February 2021, Miranda J Delahoy, Flor Munoz, De-Kun Li, Carmen Sofia Arriola, Nanette Lee Bond, Michael Daugherty, Jeannette Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Stephanie A Irving, Mary Juergens, Venkatesh Kancharla, Mara Greenberg, Roxana Odouli, Gabriella Newes-Adeyi, Erin G Nicholson, Lawrence Reichle, Momodou Sanyang, Margaret Snead, Fatimah S Dawood, Allison L Naleway

Faculty, Staff and Students Publications

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden.

METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing …

Improving Traditional Registrational Trial End Points: Development And Application Of A Desirability Of Outcome Ranking End Point For Complicated Urinary Tract Infection Clinical Trials, Jessica Howard-Anderson, Toshimitsu Hamasaki, Weixiao Dai, Deborah Collyar, Daniel Rubin, Sumathi Nambiar, Tori Kinamon, Carol Hill, Steven P Gelone, David Mariano, Takamichi Baba, Thomas L Holland, Sarah B Doernberg, Henry F Chambers, Vance G Fowler, Scott R Evans, Helen W Boucher

Faculty, Staff and Student Publications

BACKGROUND: Traditional end points used in registrational randomized, controlled trials (RCTs) often do not allow for complete interpretation of the full range of potential clinical outcomes. Desirability of outcome ranking (DOOR) is an approach to the design and analysis of clinical trials that incorporates benefits and risks of novel treatment strategies and provides a global assessment of patient experience.

METHODS: Through a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience, we developed a DOOR end point for infectious disease syndromes and demonstrated how this could be applied to 3 registrational drug trials (ZEUS, …

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Antibiotic Indications And Appropriateness In The Pediatric Intensive Care Unit: A 10-Center Point Prevalence Study, Kathleen Chiotos, Jennifer Blumenthal, Juri Boguniewicz, Debra L Palazzi, Erika L Stalets, Jessica H Rubens, Pranita D Tamma, Stephanie S Cabler, Jason Newland, Hillary Crandall, Emily Berkman, Robert P Kavanagh, Hannah R Stinson, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking.

METHODS: We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric.

RESULTS: Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic …

Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A Gimnich, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Background

Computational fluid dynamics has shown good agreement with contrast‐enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast‐enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD).

Methods and Results

The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast‐enhanced magnetic resonance imaging and ankle‐brachial index testing at rest and after 6‐minute treadmill walking. We have determined associations of microvascular model parameters including the transfer …

Hmgb1/Gpc3 Dual Targeting Vaccine Induces Dendritic Cells-Mediated Cd8+T Cell Immune Response And Elicits Potential Therapeutic Effect In Hepatocellular Carcinoma, Xiaoqing Shi, Jiage Ding, Yanyan Zheng, Jiawei Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Hepatocellular carcinoma (HCC) is a fatal malignant tumor, but effective clinical interventions are limited. PLGA/PEI-mediated DNA vaccine encoding the dual targets of high-mobility group box 1 (HMGB1) or GPC3 was developed for HCC treatment. Compared with PLGA/PEI-GPC3 immunization, PLGA/PEI-HMGB1/GPC3 co-immunization significantly inhibited the subcutaneous tumor growth, while increasing the infiltration of CD8

Muc1 Expressions And Its Prognostic Values In Us Gastric Cancer Patients, Young-Il Kim, Robert Luke Pecha, Tara Keihanian, Michael Mercado, S Valeria Pena-Munoz, Kailash Lang, George Van Buren, Sadhna Dhingra, Mohamed O Othman

Faculty, Staff and Students Publications

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and …

Genome-Wide Screening Reveals The Genetic Basis Of Mammalian Embryonic Eye Development, Justine M Chee, Louise Lanoue, Dave Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, H-J Genie Chin, Mary E Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Fabio Mammano, Lauryl M J Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin Mckerlie, K C Kent Lloyd, Henrik Westerberg, Ala Moshiri

Faculty, Staff and Students Publications

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways …

Immunogenetic Determinants Of Susceptibility To Head And Neck Cancer In The Million Veteran Program Cohort, Yanhong Liu, Jennifer R Kramer, Vlad C Sandulache, Robert Yu, Guojun Li, Liang Chen, Zenab I Yusuf, Yunling Shi, Saiju Pyarajan, Spyros Tsavachidis, Li Jiao, Michelle L Mierzwa, Elizabeth Chiao, Yvonne M Mowery, Andrew Shuman, Sanjay Shete, Andrew G Sikora, Donna L White

Faculty, Staff and Student Publications

Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and …

A Dlg1-Arhgap31-Cdc42 Axis Is Essential For The Intestinal Stem Cell Response To Fluctuating Niche Wnt Signaling, David Castillo-Azofeifa, Tomas Wald, Efren A Reyes, Aaron Gallagher, Julia Schanin, Stephanie Vlachos, Nathalie Lamarche-Vane, Carolyn Bomidi, Sarah Blutt, Mary K Estes, Todd Nystul, Ophir D Klein

Faculty, Staff and Students Publications

A central factor in the maintenance of tissue integrity is the response of stem cells to variations in the levels of niche signals. In the gut, intestinal stem cells (ISCs) depend on Wnt ligands for self-renewal and proliferation. Transient increases in Wnt signaling promote regeneration after injury or in inflammatory bowel diseases, whereas constitutive activation of this pathway leads to colorectal cancer. Here, we report that Discs large 1 (Dlg1), although dispensable for polarity and cellular turnover during intestinal homeostasis, is required for ISC survival in the context of increased Wnt signaling. RNA sequencing (RNA-seq) and genetic mouse models demonstrated …

Association Between P2y12 Inhibitor Reloading And In-Hospital Outcomes For Patients With Non-St-Segment Elevation Acute Coronary Syndrome Already On Chronic P2y12 Receptor Inhibitors Therapy In China: Findings From The Ccc-Acs (Improving Care For Cardiovascular Disease In China-Acute Coronary Syndrome) Project, Yintang Wang, Yu Geng, Ou Zhang, Qin Xu, Yajun Xue, Boda Zhou, Ping Zhang

Faculty, Staff and Student Publications

BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined.

METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted.

RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk …

Supporting Cardiac Perfusion By Preboa With Reduced Visceral Ischemia Despite Extended Occlusion, Paige Deville, John Hunt, Alan B. Marr, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alison Smith

School of Medicine Faculty Publications

No abstract provided.

Spontaneous Large Volume Hemothorax Managed With A Small-Bore Chest Tube, Moiz Salahuddin, Samia Ayub

Department of Medicine

A 67-year-old male with metastatic lung cancer presented with acute shortness of breath and increasing oxygen requirements. He had a decreasing hemoglobin for which he required red blood cell transfusions. His chest x-ray showed near complete white-out of the left lung. Bedside ultrasound (Handheld Sonostar C4PL) showed a large pleural effusion with swirling echogenic material suggestive of plankton sign. The pleural effusion was aspirated and showed frank blood, after which a small-bore chest tube (SBCT) was inserted. A total of 3200ml of blood was drained with the SBCT. There was complete clearance of the pleural space, and no further blood …

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …