Digital Commons Network^™

Plasma Microbial Cell-Free Dna Sequencing For The Detection Of Kingella Kingae Pediatric Spinal Infections, Asim A Ahmed, Sarah Y Park, Matthew J Smollin, Martin S Lindner, Adriana Sarmiento Clemente, Ana Del Valle Penella, P Marcelo Laufer, Carolina Sanchez-Vegas, Manuel R Cotilla, Marian E Melish, Connie Trieu, Nazia A Kabani, Joshua Cooper, Audrey R Lloyd, David W Kimberlin, John C Arnold, Alejandro Jordan-Villegas, Lori E Patterson, Catherine E Foster, Pablo Yagupsky

Faculty, Staff and Students Publications

Background: Diagnosis of Kingella kingae skeletal system infections is made challenging by the microbe's fastidious nature. Detection and quantification of circulating microbial cell-free DNA (mcfDNA) in plasma by the Karius Test, a commercial metagenomic sequencing test, may offer promise in diagnosing pediatric spinal infections caused by difficult-to-culture organisms such as K. kingae .

Methods: Plasma mcfDNA sequencing detections of K. kingae from April 2018 to December 2020 were reviewed to identify pediatric (age < 18 years) patients. Medical charts of those with spinal infections were reviewed, and mcfDNA sequencing diagnostic performance was compared with usual care tests (ie, cultures, polymerase chain reaction).

Results: Ten children with K. kingae spinal infections were identified across 7 institutions. The median age was 16.5 months (range 11-23 months). All case-patients had vertebral osteomyelitis …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Evaluation Of Knowledge, Attitudes And Vaccine Hesitancy Towards Mmr Vaccine Among Parents In The United Arab Emirates, Kamel A. Samara, Hiba Jawdat Barqawi, Deema M. Alhayali, Samah Mohamed Kannas, Rim M. Elmorsy, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: The Measles, Mumps, and Rubella (MMR) vaccine is highly effective, but vaccine hesitancy (VH) is a key barrier to achieving herd immunity. This study aims to assess the general attitudes and knowledge of UAE parents regarding measles and the MMR vaccine while identifying determinants of VH.

METHODOLOGY: A cross-sectional study was done from 15th April 2024 and 5th June 2024. This study recruited 462 parents residing in the UAE using convenience sampling. Recruitment occurred through various social media platforms including WhatsApp, X, and Instagram, as well as in public by approaching parents in parks and malls. Information collected included …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Covid-19 Infection History As A Risk Factor For Early Pregnancy Loss: Results From The Electronic Health Record-Based Southeast Texas Covid And Pregnancy Cohort Study, Micaela N Sandoval, Michelle R Klawans, Mackinsey A Bach, Jennifer Mikhail, Edward A Graviss, Tru Cao, Jacqueline G Parchem, Junaid Husain, Eric Boerwinkle

Faculty, Staff and Student Publications

Background: The effects of SARS-CoV-2 infection before or during pregnancy on pregnancy outcomes are still largely unknown. We hypothesized that COVID-19 in early pregnancy is a risk factor for adverse pregnancy outcomes, particularly miscarriage.

Methods: We examined the relationship between COVID-19 and adverse pregnancy outcomes, including spontaneous abortion, ectopic pregnancy, and preterm delivery in a large, retrospective, electronic health record (EHR)-based cohort, from 2019 to 2023. Generalized estimating equation modeling was performed to identify risk factors for adverse pregnancy outcomes. Study exposures included COVID-19 before pregnancy, COVID-19 during pregnancy, age, race/ethnicity, comorbidity burden, and neighborhood-level social vulnerability.

Results: In the …

Investigating Social Network Peer Effects On Hiv Care Engagement Using A Fuzzy-Like Matching Approach: Cross-Sectional Secondary Analysis Of The N2 Cohort Study, Cho-Hee Shrader, Dustin T Duncan, Redd Driver, Juan G Arroyo-Flores, Makella S Coudray, Raymond Moody, Yen-Tyng Chen, Britt Skaathun, Lindsay Young, Natascha Del Vecchio, Kayo Fujimoto, Justin R Knox, Mariano Kanamori, John A Schneider

Faculty, Staff and Student Publications

BACKGROUND: Social network data are essential and informative for public health research and implementation as they provide details on individuals and their social context. For example, health information and behaviors, such as HIV-related prevention and care, may disseminate within a network or across society. By harmonizing egocentric and digital networks, researchers may construct a sociocentric-like "fuzzy" network based on a subgroup of the population.

OBJECTIVE: We aimed to generate a more complete sociocentric-like "fuzzy" network by harmonizing alternative sources of egocentric and digital network data to examine relationships between participants in the Neighborhoods and Networks (N2) cohort study. Further, we …

Metabolic Reprogramming Driven By Ant2 Deficiency Augments T Cell Function And Anti-Tumor Immunity In Mice, Omri Yosef, Leonor Cohen-Daniel, Oded Shamriz, Zahala Bar-On, Wajeeh Salaymeh, Amijai Saragovi, Ifat Abramovich, Bella Agranovich, Veronika Lutz, Joseph Tam, Anna Permyakova, Eyal Gottlieb, Magdalena Huber, Michael Berger

Faculty, Staff and Student Publications

T cell activation requires a substantial increase in NAD+ production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generate T cell-specific ADP/ATP translocase-2 knockout (Ant2-/-) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, thereby impeding NAD+ regeneration. Interestingly, Ant2-/- naïve T cells exhibit enhanced activation, proliferation and effector functions compared to wild-type controls. Metabolic profiling reveals that these T cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Lastly, pharmacological inhibition of ANT …

Development Of A Risk Score To Aid With The Diagnosis Of Infections After Spinal Cord Injury: Protocol For A Retrospective Cohort Study, Felicia Skelton, Larissa Grigoryan, Joann Pan, Ashley Collazo, Barbara Trautner

Faculty, Staff and Students Publications

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI.

Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI.

Methods: This study will use data from the Veterans Health Administration Corporate Data …

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Graeme Segal, Stephanie Novak, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

Characterising Acute And Chronic Care Needs: Insights From The Global Burden Of Disease Study 2019, A. A. Asadi-Pooya

Department of Neurology Faculty Papers

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic …

Artificial Intelligence-Based Virtual Staining Platform For Identifying Tumor-Associated Macrophages From Hematoxylin And Eosin-Stained Images, Arpit Aggarwal, Mayukhmala Jana, Amritpal Singh, Tanmoy Dam, Himanshu Maurya, Tilak Pathak, Sandra Orsulic, Kailin Yang, Deborah Chute, Justin A Bishop, Farhoud Faraji, Wade M Thorstad, Shlomo Koyfman, Scott Steward, Qiuying Shi, Vlad Sandulache, Nabil F Saba, James S Lewis, Germán Corredor, Anant Madabhushi

Faculty, Staff and Students Publications

Background: Virtual staining is an artificial intelligence-based approach that transforms pathology images between stain types, such as hematoxylin and eosin (H&E) to immunohistochemistry (IHC), providing a tissue-preserving and efficient alternative to traditional IHC staining. However, existing methods for translating H&E to virtual IHC often fail to generate images of sufficient quality for accurately delineating cell nuclei and IHC+ regions. To address these limitations, we introduce VISTA, an artificial intelligence-based virtual staining platform designed to translate H&E into virtual IHC.

Methods: We applied VISTA to identify M2-subtype tumor-associated macrophages (M2-TAMs) in H&E images from 968 patients with HPV+ oropharyngeal squamous cell …

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse., Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David E Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Faculty Research 2025

Haematopoietic stem cells maintain blood production throughout life1 . Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which they …

An Intranasal Subunit Vaccine Induces Protective Systemic And Mucosal Antibody Immunity Against Respiratory Viruses In Mouse Models., Aina Karen Anthi, Anette Kolderup, Eline Benno Vaage, Malin Bern, Sopisa Benjakul, Elias Tjärnhage, Fulgencio Ruso-Julve, Kjell-Rune Jensen, Heidrun Elisabeth Lode, Marina Vaysburd, Jeannette Nilsen, Marie Leangen Herigstad, Siri Aastedatter Sakya, Lisa Tietze, Diego Pilati, Mari Nyquist-Andersen, Mirjam Dürkoop, Torleif Tollefsrud Gjølberg, Linghang Peng, Stian Foss, Morten C Moe, Benjamin E. Low, Michael V. Wiles, David Nemazee, Frode L Jahnsen, John Torgils Vaage, Kenneth A Howard, Inger Sandlie, Leo C James, Gunnveig Grødeland, Fridtjof Lund-Johansen, Jan Terje Andersen

Faculty Research 2025

Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked …

Maternal Cardiometabolic Risk Factors In Pregnancy And Offspring Blood Pressure At Age 2 To 18 Years., Zhongzheng Niu, Ako Adams Ako, Sarah Dee Geiger, Caitlin G. Howe, Wei Perng, Rachana Singh, Margaret R. Karagas, Amy J. Elliott, Andrea Cassidy-Bushrow, Carlos A. Camargo, Keia Sanderson, Cynthia T. Mcevoy, Emily Oken, Dana Dabelea, Tina V. Hartert, Brian S. Carter, Annemarie Stroustrup, Andrea Lampland, Thomas G. O'Connor, Semsa Gogcu, Mark L. Hudak, Lyndsey E. Shorey-Kendrick, Qi Zhao, Yu Ni, Jeffrey Vanwormer, Assiamira Ferrara, Monique Hedderson, Yeyi Zhu, Akram Alshawabkeh, Jose Cordero, Daphne Koinis-Mitchell, Susan Carnell, Carrie V. Breton, Theresa M. Bastain, Shohreh F. Farzan, Echo Cohort Consortium

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Higher blood pressure in early life may signal cardiovascular disease over the life course, but determinants of blood pressure in early life are poorly understood.

OBJECTIVE: To examine the association of maternal cardiometabolic risk factors during pregnancy with offspring blood pressure from age 2 to 18 years and explore whether the association is modified by offspring sex and race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from the Environmental Influences on Child Health Outcomes program between January 1, 1994, and March 31, 2023. Three common maternal cardiometabolic risk factors during pregnancy were examined: prepregnancy obesity, …

Enterovirus D68-Associated Respiratory Illness In Children., Benjamin R. Clopper, Adriana S. Lopez, Leah A. Goldstein, Terry Fei Fan Ng, Ariana P. Toepfer, Mary A. Staat, Elizabeth P. Schlaudecker, Leila C. Sahni, Julie A. Boom, Jennifer E. Schuster, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, John V. Williams, Marian G. Michaels, Geoffrey A. Weinberg, Peter G. Szilagyi, Eileen J. Klein, Janet A. Englund, Meredith L. Mcmorrow, Heidi L. Moline, Claire M. Midgley

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain.

OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 …

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Center on Aging Staff Publications

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which …

Overlapping Clinical Phenotypes In Patients With Primary Ciliary Dyskinesia Or Activated Phosphoinositide 3-Kinase Delta Syndrome, Adam J Shapiro, Eveline Y Wu, Deborah J Morris-Rosendahl, Kenneth N Olivier, Sharon D Dell, Scott D Sagel, Cullen M Dutmer, Ricardo A Mosquera, Markus Rose, Michael G O'Connor, Chi A Ma, Gulbu Uzel, Timothy J Vece, Maimoona A Zariwala, Michael R Knowles, Margaret W Leigh, Stephanie D Davis, Thomas W Ferkol

Faculty, Staff and Student Publications

Primary ciliary dyskinesia and activated phosphoinositide 3-kinase delta syndrome type 1 present similarly, with recurrent respiratory infections and reduced nasal nitric oxide levels. When diagnostic confirmation of primary ciliary dyskinesia with genetic testing and/or ciliary electron microscopy is inconclusive, activated phosphoinositide 3-kinase delta syndrome type 1 and other inborn errors of immunity must be investigated.

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

The Dialysis Foot- The Impact Of Presenting Estimated Glomerular Filtration Rate On Clinical Outcomes In Patients Hospitalized With Diabetic Foot Infections, Arthur Tarricone, Tyler L Coye, Allen Gee, Bijan Najafi, Michael C Siah, Lawrence A Lavery

Center on Aging Staff Publications

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR < 30 (eGFR < 30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR < 30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR < 30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR < 30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR < 30; p <  0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

Development Of A Reference Standard To Assign Bacterial Versus Viral Infection Etiology Using An All-Inclusive Methodology For Comparison Of Novel Diagnostic Tool Performance, Coburn Allen, J Kate Deanehan, Yaniv Dotan, Matthew A Eisenberg, Andrew M Fine, Jonathan Isenberg, Ann Kane, Dani Kirshner, Todd W Lyons, Yasmin Maor, Ami Neuberger, Daniel G Ostermayer, Sharona Paz, Oded Scheuerman, Shachaf Shiber, Victoria A Statler, Michal Stein, Renata Yakubov, Shirly Yanai, Roy Navon, Lior Kellerman, Tanya M Gottlieb, Eran Eden

Faculty, Staff and Student Publications

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included. Adjudicators, blinded to C-reactive protein, procalcitonin, and MeMed BV (MMBV), labeled each case (bacterial/viral/non-infectious/indeterminate). Initial adjudication involved 3 adjudicators. Reference standard cohorts were defined: Microbiologically confirmed (3/3 adjudicators concur with high confidence and a concordant microbiological finding), unanimous (3/3 adjudicators concur with high confidence), suspected (3/3 adjudicators concur with …

The Effects Of Prescribed Medications On Depressive Symptoms And Neurocognitive Performance In People With Hiv, Asante R Kamkwalala, Avery Matthews, Ankita Garg, Upal Roy, Qing Ma, Maile Karris, Erin Sundermann, Ronald J Ellis, Patricia K Riggs, Mattia Trunfio, Jennifer Blanchard, David J Moore, Leah H Rubin, Scott L Letendre

Faculty, Staff and Student Publications

Background: Alterations in brain function and structure, such as depression and neurocognitive impairment, continue to occur in people with human immunodeficiency virus (HIV, PWH) taking suppressive antiretroviral therapy (ART). The lifespan of PWH has improved but the healthspan remains worse than people without HIV, in part because of aging-related diseases. As a result, polypharmacy is common and increases the risk of drug-drug interactions and adverse reactions.

Methods: This cross-sectional project investigated the relationship between 7 medication-related metrics (including anticholinergic burden), depressive symptoms, and neurocognitive performance in 491 PWH at a single center in the United States. All participants were taking …

An Intranasally Administered Igm Protects Against Antigenically Distinct Subtypes Of Influenza A Viruses, Ashwin Kumar Ramesh, Jwala Priyadarsini Sivaccumar, Xiaohua Ye, Luona Yang, Hailong Guo, Chen-Ni Chin, Sha Ha, John W Shiver, William R Strohl, Yan Xu, Haijuan Du, Tongqing Zhou, Ningyan Zhang, Kai Xu, Xinli Liu, Tong-Ming Fu, Zhiqiang An

Faculty, Staff and Student Publications

Engineering broadly neutralizing monoclonal antibodies (mAbs) targeting the hemagglutinin (HA) of Influenza A virus (IAV) is a promising approach for intervention of seasonal flu. However, HA plasticity often leads to resistant strains that compromise mAb potency as bivalent IgGs. Here we hypothesize that multimerization of anti-IAV antibodies as IgMs can enhance coverage and neutralization potency. Here, we construct 18 IgM antibodies from known broadly neutralizing IgGs targeting different IAV HA epitopes and evaluate their breadth and potency of neutralization against distinct H1N1 and H3N2 IAVs. The IgM version of receptor binding site-specific IgG F045-092 shows increased breadth and antiviral potency …

Spectrum Of Congenital Anomalies Detected Through Anatomy Ultrasound At A Referral Hospital In Ghana, Alim Swarray-Deen, Morgan Yapundich, Sarah Boudova, Kwaku Doffour-Dapaah, Jeff Osei-Agyapong, Perez Sepenu, Alex K. Boateng, Teresa A. Mensah, Patrick Anum, Nana Essuman Oduro, Theophilus Adu-Bredu, Promise E. Sefogah, Jerry Coleman, Samuel A. Oppong

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Africa has a high burden of congenital anomalies due in part to limited preconception care, infections, and environmental exposures. However, the true prevalence of congenital anomalies is unclear because of insufficient access to prenatal diagnostic services. We aimed to determine the rate of congenital anomalies, and characterize the anomalies detected prenatally at a referral hospital in Ghana.

METHODS: We performed a four-year retrospective review of all fetal anomaly ultrasounds performed and congenital anomalies detected from January 1st, 2020, to December 31st, 2023, at Korle Bu Teaching Hospital, Accra, Ghana. Data were extracted from the electronic database on maternal age, …