Digital Commons Network^™

A Toddler With New Seizures, Progressive White Matter Lesions, And Multifocal Microhemorrhages, Dana Tlais, Stephanie Fetzko, Nitya Gulati, Huy Brandon D Tran, Sarah Risen, Yi-Chen Lai

Faculty, Staff and Students Publications

A 16-month-old, previously healthy male is hospitalized for new onset seizures. Initial investigation is significant for enterovirus/rhinovirus respiratory infection, abnormal T2 signal predominantly in the white matter and scattered microhemorrhages on brain MRI, transaminitis, and thrombocytopenia. His symptoms initially improve on steroid therapy and he is discharged from the hospital. During the ensuing month with the tapering of the steroids, he develops new motor deficits for which he is rehospitalized. His laboratory investigation on readmission is unremarkable. However, there is significant progression of white matter lesions and microhemorrhages on repeat MRI. While in the hospital, he becomes febrile and has …

Role Of Bacteriophage Therapy For Resistant Infections In Transplant Recipients, Paul Nicholls, Saima Aslam

Faculty, Staff and Students Publications

Purpose of review: Multidrug-resistant organisms (MDROs) are prevalent in transplant recipients and associated with poor outcomes. We review recent cases of phage therapy used to treat recalcitrant infections in transplant recipients and explore the future role of such therapy in this setting.

Recent findings: Individual case reports and small case series suggest possible efficacy of phage therapy for the treatment of MDRO infections in pre and posttransplant patients. Importantly, there have been no serious safety concerns in the reported cases that we reviewed. There are no applicable randomized controlled trials (RCTs) to better guide phage therapy at this time.

Summary: …

A New Chapter In An Evolving Pandemic: Successful Pediatric Liver Transplantation With Sars-Cov-2+ Donors, Matthew Benjamin Goss, Daniel Hao Bin Leung, Stephanie Marie Pouch, Flor M Munoz, Elizabeth Andrea Moulton, Tyler Malcolm Mccann Lambing, Sarah Koohmaraie, Nicolas Fernando Moreno, Christine A O'Mahony, John A Goss, Nhu Thao Nguyen Galván

Faculty, Staff and Students Publications

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors.

METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform.

RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a …

Foxi3 Haploinsufficiency Contributes To Low T-Cell Receptor Excision Circles And T-Cell Lymphopenia, Rajarshi Ghosh, Marita Bosticardo, Sunita Singh, Morgan Similuk, Ottavia M Delmonte, Francesca Pala, Christine Peng, Colleen Jodarski, Michael D Keller, Ivan K Chinn, Andrew K Groves, Luigi D Notarangelo, Magdalena A Walkiewicz, Javier Chinen, Vanessa Bundy

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening can identify neonatal T-cell lymphopenia through detection of a low number of copies of T-cell receptor excision circles in dried blood spots collected at birth. After a positive screening result, further diagnostic testing is required to determine whether the subject has severe combined immunodeficiency or other causes of T-cell lymphopenia. Even after thorough evaluation, approximately 15% of children with a positive result of newborn screening for T-cell receptor excision circles remain genetically undiagnosed. Identifying the underlying genetic etiology is necessary to guide subsequent clinical management and family planning.

OBJECTIVE: We sought to elucidate the genetic basis of …

Histopathologic And Transcriptomic Phenotypes Of A Conditional Rankl Transgenic Mouse Thymus, Maria M Szwarc, Lan Hai, Vineet K Maurya, Kimal Rajapakshe, Dimuthu Perera, Michael M Ittmann, Qianxing Mo, Yong Lin, Matthew L Bettini, Cristian Coarfa, John P Lydon

Faculty, Staff and Students Publications

Although conventional knockout and transgenic mouse models have significantly advanced our understanding of Receptor Activator of NF-κB Ligand (RANKL) signaling in intra-thymic crosstalk that establishes self-tolerance and later stages of lymphopoiesis, the unique advantages of conditional mouse transgenesis have yet to be explored. A main advantage of conditional transgenesis is the ability to express a transgene in a spatiotemporal restricted manner, enabling the induction (or de-induction) of transgene expression during predetermined stages of embryogenesis or during defined postnatal developmental or physiological states, such as puberty, adulthood, and pregnancy. Here, we describe the K5: RANKL bigenic mouse, in which transgene derived …

The Us Department Of Veterans Affairs Science And Health Initiative To Combat Infectious And Emerging Life-Threatening Diseases (Va Shield): A Biorepository Addressing National Health Threats, John B Harley, Saiju Pyarajan, Elizabeth S Partan, Lauren Epstein, Jason A Wertheim, Abhinav Diwan, Christopher W Woods, Victoria Davey, Sharlene Blair, Dennis H Clark, Kenneth M Kaufman, Shagufta Khan, Iouri Chepelev, Alexander Devine, Perry Cameron, Monica F Mccann, Mary Cloud B Ammons, Devin D Bolz, Jane K Battles, Jeffrey L Curtis, Mark Holodniy, Vincent C Marconi, Charles D Searles, David O Beenhouwer, Sheldon T Brown, Jonathan P Moorman, Zhi Q Yao, Maria C Rodriguez-Barradas, Shyam Mohapatra, Osmara Y Molina De Rodriguez, Emerson B Padiernos, Eric R Mcindoo, Emily Price, Hailey M Burgoyne, Ian Robey, Dawn C Schwenke, Carey L Shive, Ronald M Przygodzki, Rachel B Ramoni, Holly K Krull, Robert A Bonomo

Faculty, Staff and Students Publications

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 …

Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …

Qualitative Analysis Of A Twitter-Disseminated Survey Reveals New Patient Perspectives On The Impact Of Urinary Tract Infection, Marissa Valentine-King, Lindsey Laytner, Casey Hines-Munson, Kiara Olmeda, Barbara Trautner, Sheryl Justice, Christina Ching, Larissa Grigoryan

Faculty, Staff and Students Publications

Few studies have harnessed social media to explore patients’ experiences with urinary tract infection (UTI); therefore, we captured UTI experiences and future research suggestions through a Twitter-disseminated survey. The survey posed three qualitative questions inquiring about the impact of UTIs, greatest UTI management hurdle, and research suggestions. We also asked participants to rate how seriously others perceive UTIs and the importance of UTIs in their life (scale: 1–100 (highest)). The study period spanned from January to June 2021. Coding was performed in duplicate, followed by thematic analysis. Of 466 participants from 22 countries, 128 considered their UTIs recurrent (n …

Depletion Of Cd206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation And Muscle Regeneration, Allah Nawaz, Muhammad Bilal, Shiho Fujisaka, Tomonobu Kado, Muhammad Rahil Aslam, Saeed Ahmed, Keisuke Okabe, Yoshiko Igarashi, Yoshiyuki Watanabe, Takahide Kuwano, Koichi Tsuneyama, Ayumi Nishimura, Yasuhiro Nishida, Seiji Yamamoto, Masakiyo Sasahara, Johji Imura, Hisashi Mori, Martin M Matzuk, Fujimi Kudo, Ichiro Manabe, Akiyoshi Uezumi, Takashi Nakagawa, Yumiko Oishi, Kazuyuki Tobe

Faculty, Staff and Students Publications

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in …

High Throughput Sequencing For Clinical Tuberculosis: An Overview, Tara E Ness, Andrew Dinardo, Maha R Farhat

Faculty, Staff and Students Publications

High throughput sequencing (HTS) can identify the presence of Mycobacterium tuberculosis DNA in a clinical sample while also providing information on drug susceptibility. Multiple studies have provided a context for exploring the clinical application of HTS for TB diagnosis. The workflow challenges, strengths and limitations of the various sequencing platforms, and tools used for analysis are presented to provide a framework for further innovations in the field.

Clinical And In Vitro Evidence Favoring Immunoglobulin Treatment Of A Chronic Norovirus Infection In A Patient With Common Variable Immunodeficiency, Jeroen J A Van Kampen, Virgil A S H Dalm, Pieter L A Fraaij, Bas B Oude Munnink, Claudia M E Schapendonk, Ray W Izquierdo-Lara, Nele Villabruna, Khalil Ettayebi, Mary K Estes, Marion P G Koopmans, Miranda De Graaf

Faculty, Staff and Students Publications

BACKGROUND: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available.

METHODS: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced.

RESULTS: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation …

Repeated Out-Of-Africa Expansions Of Helicobacter Pylori Driven By Replacement Of Deleterious Mutations, Harry A Thorpe, Elise Tourrette, Koji Yahara, Filipa F Vale, Siqi Liu, Mónica Oleastro, Teresa Alarcon, Tsachi-Tsadok Perets, Saeid Latifi-Navid, Yoshio Yamaoka, Beatriz Martinez-Gonzalez, Ioannis Karayiannis, Timokratis Karamitros, Dionyssios N Sgouras, Wael Elamin, Ben Pascoe, Samuel K Sheppard, Jukka Ronkainen, Pertti Aro, Lars Engstrand, Lars Agreus, Sebastian Suerbaum, Kaisa Thorell, Daniel Falush

Faculty, Staff and Students Publications

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying …

Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.

METHODS: Atovaquone was extracted from a 10 µL volume of K

RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

Disease Progression Of Whim Syndrome In An International Cohort Of 66 Pediatric And Adult Patients, Christoph B Geier, Maryssa Ellison, Rachel Cruz, Sumit Pawar, Alexander Leiss-Piller, Katarina Zmajkovicova, Shannon M Mcnulty, Melis Yilmaz, Martin Oman Evans, Sumai Gordon, Boglarka Ujhazi, Ivana Wiest, Hassan Abolhassani, Asghar Aghamohammadi, Sara Barmettler, Saleh Bhar, Anastasia Bondarenko, Audrey Anna Bolyard, David Buchbinder, Michaela Cada, Mirta Cavieres, James A Connelly, David C Dale, Ekaterina Deordieva, Morna J Dorsey, Simon B Drysdale, Stephan Ehl, Reem Elfeky, Francesca Fioredda, Frank Firkin, Elizabeth Förster-Waldl, Bob Geng, Vera Goda, Luis Gonzalez-Granado, Eyal Grunebaum, Elzbieta Grzesk, Sarah E Henrickson, Anna Hilfanova, Mitsuteru Hiwatari, Chihaya Imai, Winnie Ip, Soma Jyonouchi, Hirokazu Kanegane, Yuta Kawahara, Amer M Khojah, Vy Hong-Diep Kim, Marina Kojić, Sylwia Kołtan, Gergely Krivan, Daman Langguth, Yu-Lung Lau, Daniel Leung, Maurizio Miano, Irina Mersyanova, Talal Mousallem, Mica Muskat, Flavio A Naoum, Suzie A Noronha, Monia Ouederni, Shuichi Ozono, G Wendell Richmond, Inga Sakovich, Ulrich Salzer, Catharina Schuetz, Filiz Odabasi Seeborg, Svetlana O Sharapova, Katja Sockel, Alla Volokha, Malte Von Bonin, Klaus Warnatz, Oliver Wegehaupt, Geoffrey A Weinberg, Ke-Juin Wong, Austen Worth, Huang Yu, Yulia Zharankova, Xiaodong Zhao, Lisa Devlin, Adriana Badarau, Krisztian Csomos, Marton Keszei, Joao Pereira, Arthur G Taveras, Sarah L Beaussant-Cohen, Mei-Sing Ong, Anna Shcherbina, Jolan E Walter

Faculty, Staff and Students Publications

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not …

Race, Racism, And Antiracism In Emergency Medicine: A Scoping Review Of The Literature And Research Agenda For The Future, Anna Darby, Emily C Cleveland Manchanda, Hannah Janeway, Shamsher Samra, Marquita Norman Hicks, Ruby Long, Katrina A Gipson, Anita N Chary, Brenda A Adjei, Kajal Khanna, Ava Pierce, Sheri-Ann O Kaltiso, Sophia Spadafore, Jennifer Tsai, Annette Dekker, Molly E Thiessen, Jordan Foster, Rose Diaz, Mikaela Mizuno, Elizabeth Schoenfeld

Faculty, Staff and Students Publications

Objectives: The objective was to conduct a scoping review of the literature and develop consensus-derived research priorities for future research inquiry in an effort to (1) identify and summarize existing research related to race, racism, and antiracism in emergency medicine (EM) and adjacent fields and (2) set the agenda for EM research in these topic areas.

Methods: A scoping review of the literature using PubMed and EMBASE databases, as well as review of citations from included articles, formed the basis for discussions with community stakeholders, who in turn helped to inform and shape the discussion and recommendations of participants in …

Re-Examining The Widespread Policy Of Stopping Sodium-Glucose Cotransporter-2 Inhibitors During Acute Illness: A Perspective Based On The Updated Evidence, Kamlesh Khunti, Vanita R Aroda, Deepak L Bhatt, Biykem Bozkurt, John B Buse, Hiddo L Heerspink, Silvio E Inzucchi, Carolyn S P Lam, Nikolaus Marx, John J V Mcmurray, Scott D Solomon, Mikhail N Kosiborod

Faculty, Staff and Students Publications

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or …

Letter To The Editor, Magdalene M Assimon, Patrick H Pun, Lily Wang, Sana M Al-Khatib, M Alan Brookhart, David J Weber, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

No abstract provided.

Successful Use Of Continuous Erector Spinae Plane Blocks In A Patient With Variant Angina After Large Ventral Hernia Repair, Alexandra L Belfar, Yi Deng, Raymond C Yu, Annas Sabbagh

Faculty, Staff and Students Publications

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a …

Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is an estrogen-dependent inflammatory disease that develops in reproductive-aged women who experience pelvic pain and infertility. Even though endometriosis is not a new disease, its molecular etiology has not been clearly elucidated. Defects in the immune system might be one of the factors that promote endometriosis progression. For example, elevated levels of proinflammatory cytokines are associated with endometriosis. Interferon is one of the cytokines that is elevated in endometriotic tissues compared with normal endometrium. Therefore, high interferon levels play a crucial role in endometriosis progression. In addition to endometriosis, however, interferon has a critical role in endometrial function, particularly …

Spatial Profiling Of The Prostate Cancer Tumor Microenvironment Reveals Multiple Differences In Gene Expression And Correlation With Recurrence Risk, Vinay Kumar, Pavneet Randhawa, Robert Bilodeau, Dan Mercola, Michael Mcclelland, Anshu Agrawal, James Nguyen, Patricia Castro, Michael M Ittmann, Farah Rahmatpanah

Faculty, Staff and Students Publications

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.

Crucial Nuances In Understanding (Mis)Associations Between The Neonatal Microbiome And Cesarean Delivery, Alexa M Sassin, Grace J Johnson, Alison N Goulding, Kjersti M Aagaard

Faculty, Staff and Students Publications

As rates of Cesarean delivery and common non-communicable disorders (NCDs), such as obesity, metabolic disease, and atopy/asthma, have concomitantly increased in recent decades, investigators have attempted to discern a causal link. One line of research has led to a hypothesis that Cesarean birth disrupts the presumed normal process of colonization of the neonatal microbiome with vaginal microbes, yielding NCDs later in life. However, a direct link between a disrupted microbiota transfer at time of delivery and acute and/or chronic illness in infants born via Cesarean has not been causally established. Microbiota seeding from maternal vaginal or stool sources has been …

The Association Of Baseline Plasma Sars-Cov-2 Nucleocapsid Antigen Level And Outcomes In Patients Hospitalized With Covid-19, Angela J Rogers, Deborah Wentworth, Andrew Phillips, Katy Shaw-Saliba, Robin L Dewar, Neil R Aggarwal, Abdel G Babiker, Weizhong Chang, Nila J Dharan, Victoria J Davey, Elizabeth S Higgs, Norman Gerry, Adit A Ginde, J W Awori Hayanga, Helene Highbarger, Jeroen L Highbarger, Mamta K Jain, Virginia Kan, Kami Kim, Perrine Lallemand, Bradley G Leshnower, Joseph K Lutaakome, Gail Matthews, Ahmad Mourad, Eleftherios Mylonakis, Ven Natarajan, Maria L Padilla, Lavannya M Pandit, Roger Paredes, Sarah Pett, Srikanth Ramachandruni, M Tauseef Rehman, Brad T Sherman, D Clark Files, Samuel M Brown, Michael A Matthay, B Taylor Thompson, James D Neaton, H Clifford Lane, Jens D Lundgren

Faculty, Staff and Students Publications

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.

OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.

DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.

SETTING: 114 centers in 10 countries. …

Genome Interpretation Using In Silico Predictors Of Variant Impact, Panagiotis Katsonis, Kevin Wilhelm, Amanda Williams, Olivier Lichtarge

Faculty, Staff and Students Publications

Estimating the effects of variants found in disease driver genes opens the door to personalized therapeutic opportunities. Clinical associations and laboratory experiments can only characterize a tiny fraction of all the available variants, leaving the majority as variants of unknown significance (VUS). In silico methods bridge this gap by providing instant estimates on a large scale, most often based on the numerous genetic differences between species. Despite concerns that these methods may lack reliability in individual subjects, their numerous practical applications over cohorts suggest they are already helpful and have a role to play in genome interpretation when used at …

Socioeconomic And Comorbid Factors Affecting Mortality And Length Of Stay In Covid-19 Patients, Adam Delora, Ashlynn Mills, David Jacobson, Brendon Cornett, William F Peacock, Anita Datta, Shane P Jenks

Faculty, Staff and Students Publications

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic exposed and exacerbated health disparities between socioeconomic groups. Our purpose was to determine if age, sex, race, insurance, and comorbidities predicted patients' length of stay (LOS) in the hospital and in-hospital mortality in patients diagnosed with coronavirus disease 2019 (COVID-19) during the early pandemic. Methods Utilizing retrospective, secondarily sourced electronic health record (EHR) data for patients who tested positive for COVID-19 from HCA Healthcare facilities, predictors of LOS and in-hospital mortality were assessed using regression. LOS and in-hospital mortality were assessed using logistic regression and negative binomial regression, respectively. All …

Prevalence And Predictors Of Urine Culture Contamination In Primary Care: A Cross-Sectional Study, Michael A Hansen, Marissa Valentine-King, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth L Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Antimicrobial resistance is a global health threat. To slow resistance and preserve antibiotics, stewardship interventions are increasingly promoted and mandated. Urine cultures are the most common microbiological test in the outpatient setting. Contamination most likely occurs during urine collection from surrounding vaginal, perineal, and epidermal flora. Sample contamination can lead to incorrect diagnosis, unnecessary or inappropriate treatment, poor patient outcomes, and higher costs. Therefore, ensuring proper collection of urinary samples serves as a prime diagnostic stewardship target, one that international nursing societies increasingly endorse as an opportunity for nurse involvement.

OBJECTIVES: Determine the prevalence, predictors, and antibiotic prescribing associated …

The Association Of Baseline Plasma Sars-Cov-2 Nucleocapsid Antigen Level And Outcomes In Patients Hospitalized With Covid-19, Activ-3/Tico Study Group, Angela J Rogers, Deborah Wentworth, Andrew Phillips, Katy Shaw-Saliba, Robin L Dewar, Neil R Aggarwal, Abdel G Babiker, Weizhong Chang, Nila J Dharan, Victoria J Davey, Elizabeth S Higgs, Norman Gerry, Adit A Ginde, J W Awori Hayanga, Helene Highbarger, Jeroen L Highbarger, Mamta K Jain, Virginia Kan, Kami Kim, Perrine Lallemand, Bradley G Leshnower, Joseph K Lutaakome, Gail Matthews, Ahmad Mourad, Eleftherios Mylonakis, Ven Natarajan, Maria L Padilla, Lavannya M Pandit, Roger Paredes, Sarah Pett, Srikanth Ramachandruni, M Tauseef Rehman, Brad T Sherman, D Clark Files, Samuel M Brown, Michael A Matthay, B Taylor Thompson, James D Neaton, H Clifford Lane, Jens D Lundgren

Faculty, Staff and Students Publications

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.

OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.

DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.

SETTING: 114 centers in 10 countries. …

Azithromycin Use Increases The Risk Of Sudden Cardiac Death In Patients With Hemodialysis-Dependent Kidney Failure, Magdalene M Assimon, Patrick H Pun, Lily Wang, Sana M Al-Khatib, M Alan Brookhart, David J Weber, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007–2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …