Medical Specialties Commons^™

Handling Informative Premature Treatment Or Study Discontinuation For Assessing Between-Group Differences In A Comparative Oncology Trial, Bo Huang, Ryan Sun, Brian Claggett, Lu Tian, Ethan B Ludmir, Lee-Jen Wei

Faculty, Staff and Student Publications

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.

Targeted Inhibition Of Dna-Pkcs, Atm, Atr, Parp, And Rad51 Modulate Response To X Rays And Protons, Scott J Bright, David B Flint, David K J Martinus, Broderick X Turner, Mandira Manandhar, Mariam Ben Kacem, Conor H Mcfadden, Timothy A Yap, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects. In this study we screened the response to X-ray or proton radiation in cell lines treated with DDR inhibitors (DDRis) targeting ATM, ATR, DNA-PKcs, Rad51, …

The Impact Of Intraoperative Glucagon On The Diagnostic Accuracy Of Intraoperative Cholangiogram For The Diagnosis Of Choledocholithiasis: Experience From A Large Tertiary Care Center, Artem Boyev, Srinivas Sanjeevi, Martha M Estrada, Tien C Ko, Curtis J Wray

Faculty, Staff and Student Publications

INTRODUCTION: In response to the COVID-19 pandemic, hospitals reported decreased admissions for acute surgical diagnoses, but scant data was available to quantify the decrease and its consequences. The objective of this study was to examine the incidence of acute care surgery encounters before and during the COVID-19 pandemic.

MATERIALS AND METHODS: A retrospective cohort study was performed at a single, urban, United States safety-net hospital. Emergency room encounters, admissions, non-elective surgical procedures, patient acuity, and surgical complications were compared before and after the start of the COVID-19 pandemic. The primary outcome of the study was the incidence rate (IR) and …

A Retrospective Analysis Of Ebv-Dna Status With The Prognosis Of Lymphoma, Lihua Qiu, Junqi Si, Junnan Kang, Zehui Chen, Rexidan Nuermaimaiti, Zhengzi Qian, Lanfang Li, Shiyong Zhou, Mingjian James You, Huilai Zhang, Chen Tian

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) infection is proved to be associated with clinicopathology of lymphoma. However, little is known about the relationship between EBV-DNA status after treatment and prognosis. In this study, real-time polymerase chain reaction (PCR) was used for quantitative detection of EBV-DNA load in peripheral blood of all 26,527 patients with lymphoma, and the clinical characteristics and prognosis of 202 patients were retrospectively analysed, including 100 patients with positive EBV-DNA and 102 randomly selected patients with negative EBV-DNA. We found that the average rate of EBV-DNA positivity in lymphomas was 0.376%, and EBV-DNA-positive patients presented higher risk with elevated lactate …

Lurbinectedin, A Selective Inhibitor Of Oncogenic Transcription, In Patients With Pretreated Germline Brca1/2 Metastatic Breast Cancer: Results From A Phase Ii Basket Study, V Boni, B Pistilli, I Braña, G I Shapiro, J Trigo, V Moreno, D Castellano, C Fernández, C Kahatt, V Alfaro, M Siguero, A Zeaiter, F Longo, K Zaman, A Antón, A Paredes, G Huidobro, V Subbiah

Faculty, Staff and Student Publications

Background: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer.

Patients and methods: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival …

Systematically Higher Ki67 Scores On Core Biopsy Samples Compared To Corresponding Resection Specimen In Breast Cancer: A Multi-Operator And Multi-Institutional Study, Balazs Acs, Samuel C Y Leung, Kelley M Kidwell, Indu Arun, Renaldas Augulis, Sunil S Badve, Yalai Bai, Anita L Bane, John M S Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C Chang, Robin L Dietz, Andrew Dodson, Susan Fineberg, Cornelia M Focke, Dongxia Gao, Allen M Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Lænkholm, Arvydas Laurinavicius, Richard M Levenson, Rustin Mahboubi-Ardakani, Mauro G Mastropasqua, Sharon Nofech-Mozes, C Kent Osborne, Frédérique M Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert Van Der Vegt, Giuseppe Viale, Lila A Zabaglo, Daniel F Hayes, Mitch Dowsett, Torsten O Nielsen, David L Rimm, International Ki67 In Breast Cancer Working Group Of The Breast International Group And North American Breast Cancer Group (Big-Nabcg)

Faculty, Staff and Students Publications

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut …

Incidence And 5-Year Survival Of Children And Adolescents With Hepatoblastoma In The United States, Justin A Kahla, David A Siegel, Shifan Dai, Philip J Lupo, Jennifer H Foster, Michael E Scheurer, Andras A Heczey

Center for Medical Ethics and Health Policy Staff Publications

Objective: Hepatoblastoma (HB) is the most common pediatric primary malignant liver tumor, its incidence has been increasing worldwide, but recent changes in incidence and outcomes with high population coverage are not well characterized.

Methods: We defined the incidence of HB diagnosed during 2003-2017 from United States Cancer Statistics (USCS) database, and survival during 2001-2016 from the National Program of Cancer Registries (NPCR). Data were stratified by sex, race/ethnicity, age, tumor stage, county population, and diagnosis year. Incidence trends were assessed by calculating average annual percent change (AAPC) using Joinpoint regression. Differences in overall 5-year survival were estimated using Cox regression …

Association Of Pd-L1 Expression And Other Variables With Benefit From Immune Checkpoint Inhibition In Advanced Gastroesophageal Cancer: Systematic Review And Meta-Analysis Of 17 Phase 3 Randomized Clinical Trials, Harry H Yoon, Zhaohui Jin, Oudom Kour, Lionel Aurelien Kankeu Fonkoua, Kohei Shitara, Michael K Gibson, Larry J Prokop, Markus Moehler, Yoon-Koo Kang, Qian Shi, Jaffer A Ajani

Faculty, Staff and Student Publications

Importance: Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.

Objective: To systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.

Data sources: MEDLINE, Embase, Scopus, Web of Science, Cochrane …

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 …

The Development And Initial Validation Of The Promis®+Hf-27 And Promis+Hf-10 Profiles, Faraz S Ahmad, Kathryn L Jackson, Susan E Yount, Nan E Rothrock, Michael A Kallen, Leilani Lacson, Karl Y Bilimoria, Abel N Kho, Raja Kannan Mutharasan, Peter A Mccullough, Jeffrey Bruckel, Savitri Fedson, Stephen E Kimmel, David T Eton, Kathleen L Grady, Clyde W Yancy, David Cella

Center for Medical Ethics and Health Policy Staff Publications

Aims: Heart failure (HF) is a common and morbid condition impacting multiple health domains. We previously reported the development of the PROMIS®-Plus-HF (PROMIS+HF) profile measure, including universal and HF-specific items. To facilitate use, we developed shorter, PROMIS+HF profiles intended for research and clinical use.

Methods and results: Candidate items were selected based on psychometric properties and symptom range coverage. HF clinicians (n = 43) rated item importance and clinical actionability. Based on these results, we developed the PROMIS+HF-27 and PROMIS+HF-10 profiles with summary scores (0-100) for overall, physical, mental, and social health. In a cross-sectional sample (n = 600), we …

Residence In A Latinx Enclave And End-Induction Minimal Residual Disease Positivity Among Children With Acute Lymphoblastic Leukemia, Joshua P Muñiz, John P Woodhouse, Amy E Hughes, Sandi L Pruitt, Karen R Rabin, Michael E Scheurer, Philip J Lupo, Jeremy M Schraw

Center for Medical Ethics and Health Policy Staff Publications

Racial and ethnic inequities in survival persist for children with acute lymphoblastic leukemia (ALL). In the US, there are strong associations between SES, race/ethnicity, and place of residence. This is evidenced by ethnic enclaves: neighborhoods with high concentrations of ethnic residents, immigrants, and language isolation. The Latinx enclave index (LEI) can be used to investigate how residence in a Latinx enclave is associated with health outcomes. We studied the association between LEI score and minimal residual disease (MRD) in 142 pediatric ALL patients treated at Texas Children's Hospital. LEI score was associated with end-induction MRD positivity (OR per unit increase …

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. …

Heart Failure-Type Symptom Scores In Chronic Kidney Disease: The Importance Of Body Mass Index, Carl P Walther, Julia S Benoit, L Parker Gregg, Nisha Bansal, Vijay Nambi, Harold I Feldman, Michael G Shlipak, Sankar D Navaneethan

Faculty, Staff and Students Publications

Objectives: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD).

Background: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort.

Methods: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire …

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 …

[Nomenclature For Kidney Function And Kidney Diseases - Improving Assessment And Prognosis Through Precision And Comprehensibility], Kai-Uwe Eckardt, Isabelle Binet, Kirsten De Groot, Jürgen Floege, Jan C Galle, Isabelle Jordans, Andreas Kribben, Rainer Oberbauer, Hermann Pavenstädt, Alexander Rosenkranz, Marcus Säemann, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Kidney disease represents an increasing global health problem. Its mitigation requires effective communication between all stakeholders involved in assessment, diagnosis and therapy and individuals affected by kidney disease. However, as of today the nomenclature for kidney function and kidney disease is far from uniform. In 2019, the international non-profit organization Kidney Disease: Improving Global Outcomes (KDIGO) has implemented a consensus process to develop a glossary in English language to standardize the nomenclature for kidney function, kidney structure and kidney disease. Guiding principles for this process were (1) precision, (2) patient-centeredness and (3) consistency with KDIGO guidelines. The current position paper …

Children With Functional Abdominal Pain Disorders Successfully Decrease Fodmap Food Intake On A Low Fodmap Diet With Modest Improvements In Nutritional Intake And Diet Quality, Vishnu Narayana, Ann R Mcmeans, Rona L Levy, Robert J Shulman, Bruno P Chumpitazi

Faculty, Staff and Students Publications

BACKGROUND: We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD).

METHODS: Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined.

KEY RESULTS: Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: …

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 …

From World War Ii To Covid-19: A Historical Perspective On The American Medical Supply Chain, Hunter D Bechtold, Andrea T Cruz, Brent D Kaziny

Faculty, Staff and Students Publications

COVID-19 is the latest episode of shortages of critical medical supplies. Historically and to the present day, medical supplies have been sourced from single regions in the world, thus rendering the supply chain vulnerable to a myriad of harmful circumstances. We argue that shortages in medications related and unrelated to COVID have illustrated the need for the United States to diversify its medical supply sources before future pandemics, political crises, or natural disasters occur.

Association Of Renin Angiotensin Aldosterone System Inhibitors And Outcomes Of Hospitalized Patients With Covid-19, Neha Gupta, Lisa Settle, Brent R Brown, Donna L Armaignac, Michael Baram, Nicholas E Perkins, Margit Kaufman, Roman R Melamed, Amy B Christie, Valerie C Danesh, Joshua L Denson, Sreekanth R Cheruku, Karen Boman, Vikas Bansal, Vishakha K Kumar, Allan J Walkey, Juan P Domecq, Rahul Kashyap, Christopher E Aston

Faculty, Staff and Student Publications

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19.

DESIGN: Retrospective observational study.

SETTING: Multicenter, international COVID-19 registry.

SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during …

Cardiac Crises: Cardiac Arrhythmias And Cardiomyopathy During Tango2 Deficiency Related Metabolic Crises, Christina Y Miyake, Erica J Lay, Cheyenne M Beach, Scott R Ceresnak, Caridad M Delauz, Taylor S Howard, Christopher M Janson, Kate Jardine, Prince J Kannankeril, Maina Kava, Jeffrey J Kim, Leonardo Liberman, Scott L Macicek, Tam Dam Pham, Terry Robertson, Santiago O Valdes, Gregory Webster, Sara B Stephens, Diana M Milewicz, Mahshid Azamian, Saad A Ehsan, Kimberly M Houck, Claudia Soler-Alfonso, Kevin E Glinton, Mustafa Tosur, Na Li, Weiyi Xu, Seema R Lalani, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking.

OBJECTIVE: The purpose of this study was to describe TDD-related cardiac crises.

METHODS: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises.

RESULTS: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all …

Evidence Of Phone Vs Video-Conferencing For Mental Health Treatments: A Review Of The Literature, Patricia V Chen, Ashley Helm, Steve G Caloudas, Anthony Ecker, Giselle Day, Julianna Hogan, Jan Lindsay

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The goal of this paper is to provide a comparative review of using phone (audio-only) or video for mental health treatments. Our review includes evidence of phone and video's effectiveness in terms of reduced symptomology, retention, satisfaction, therapeutic alliance, and other outcomes of interest. This review also discusses how patients and providers' experiences and attitudes differ between these two modalities. Finally, we present information on different usage rates of phone and video across patient populations and mental health provider types, and different implementation strategies.

RECENT FINDINGS: Treatments through phone and video are both able to reduce symptoms …

First Steps: Primary Outcomes Of A Randomized, Stepped-Care Behavioral Clinical Trial For Parents Of Young Children With New-Onset Type 1 Diabetes, Marisa E Hilliard, Carrie Tully, Maureen Monaghan, Tom Hildebrandt, Christine H Wang, John R Barber, Lauren Clary, Katherine Gallagher, Wendy Levy, Fran Cogen, Celia Henderson, Lefkothea Karaviti, Randi Streisand

Faculty, Staff and Students Publications

OBJECTIVE: Despite the emotional challenges of parental adjustment to a child's type 1 diabetes diagnosis and the unique complexities of early childhood, there are few programs designed to meet the needs of parents of young children at new onset. This study evaluated First STEPS (Study of Type 1 in Early childhood and Parenting Support), a stepped-care behavioral intervention designed to support parents' psychosocial functioning and promote children's glycemic outcomes.

RESEARCH DESIGN AND METHODS: Using a two-site randomized clinical trial design, parents (n = 157) of children aged 1-6 years completed baseline data within 2 months of diabetes diagnosis and were …

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 …

Covid Community-Engaged Testing In Alabama: Reaching Underserved Rural Populations Through Collaboration, Christopher Greer Mccollum, Thomas N Creger, Aadia I Rana, Lynn T Matthews, Stefan D Baral, Greer A Burkholder, William A Curry, Latesha Elopre, Faith E Fletcher, Sydney Grooms, Emily B Levitan, Max Michael, Barbara Van Der Pol, Michael J Mugavero

Faculty, Staff and Students Publications

Rural communities are often underserved by public health testing initiatives in Alabama. As part of the National Institutes of Health's Rapid Acceleration of Diagnostics‒Underserved Populations initiative, the University of Alabama at Birmingham, along with community partners, sought to address this inequity in COVID-19 testing. We describe the participatory assessment, selection, and implementation phases of this project, which administered more than 23 000 COVID-19 tests throughout the state, including nearly 4000 tests among incarcerated populations. (

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. …

Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent …

Mixed Random And Nonrandom Allocation, And Group Randomization Have Been Mislabeled And Misanalysed, Necessitating Reanalysis Comment On Conner Et Al Kiwic For Vitality: Results Of A Randomized Placebo-Controlled Trial Testing The Effects Of Kiwifruit Or Vitamin C Tablets On Vitality In Adults With Low Vitamin C Levels, Colby J Vorland, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

We read the report by Conner and colleagues that tested whether kiwifruit or vitamin C affected measures of vitality [...].

Sequencing Individual Genomes With Recurrent Genomic Disorder Deletions: An Approach To Characterize Genes For Autosomal Recessive Rare Disease Traits, Bo Yuan, Katharina V Schulze, Nurit Assia Batzir, Jefferson Sinson, Hongzheng Dai, Wenmiao Zhu, Francia Bocanegra, Chin-To Fong, Jimmy Holder, Joanne Nguyen, Christian P Schaaf, Yaping Yang, Weimin Bi, Christine Eng, Chad Shaw, James R Lupski, Pengfei Liu

Children’s Nutrition Research Center Staff Publications

Background: In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics.

Methods: We constructed a genome-wide map for nonallelic homologous recombination (NAHR)-mediated recurrent genomic deletions and used this map to estimate population frequencies of NAHR deletions based on large-scale population cohorts and region-specific studies. We calculated recessive disease carrier burden using high-quality pathogenic or likely pathogenic variants from ClinVar and gnomAD. We developed a NIRD (NAHR deletion Impact to Recessive Disease) score for recessive …

Modeling Multivariate Age-Related Imaging Variables With Dependencies, Hwiyoung Lee, Chixiang Chen, Peter Kochunov, Liyi Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations …

Characteristics Of Community-Acquired Carbapenem-Resistant Enterobacterales, Rima Shrestha, Courtney L Luterbach, Weixiao Dai, Lauren Komarow, Michelle Earley, Gregory Weston, Erica Herc, Jesse T Jacob, Robert Salata, Darren Wong, Deverick Anderson, Kirsten B Rydell, Cesar A Arias, Liang Chen, David Van Duin, Mdro Investigators

Faculty, Staff and Student Publications

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat.

METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling.

RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was …