Digital Commons Network^™

Cefepime Pharmacokinetics In Critically Ill Children With Multiple Organ Dysfunction Syndrome Using Volumetric Absorptive Microsampling, Victor Amajor, Amanda Bwint, Steven Shein, Janet Hume, Courtney Rowan, Leeanne Flygt, Matthew Malone, Erin Stenson, Scott Weiss, Matt Zinter, Sujatha Kannan, Mary Dahmer, Ryan Nofziger, Manjunath Pai, Athena Zuppa, Nathaniel Rhodes, Mark Hall, Marc Scheetz, Kevin Downes

Department of Pediatrics Faculty Papers

Up to half of critically ill children experience multiple organ dysfunction syndrome (MODS), which worsens outcomes and increases mortality risk. Cefepime is a broad-spectrum antibiotic commonly used in pediatric sepsis, but its pharmacokinetics during MODS has not been evaluated. We performed a prospective, observational study of critically ill children with MODS who were administered cefepime and collected up to 15 whole blood samples over 3 days using volumetric absorptive microsampling (VAMS). We performed nonlinear mixed-effects modeling to develop a population PK model for cefepime in children with MODS. We then reran our final population PK model using estimated plasma concentrations …

Clinical Features And Dental Pathologies In Maxillary Sinus Fungal Balls And Odontogenic Sinusitis, Eunice Im, Lane Donaldson, Avraham Adelman, Nithin D Adappa, Yi-Wei Chen, Nikita Chapurin, Jennifer E Douglas, Glen E D'Souza, Jacob Eide, Maria Espinosa, Chia-Hsiang Fu, Meha G Fox, Rohit Garg, Edward C Kuan, Michael A Kohanski, Marta Kwiatkowska, Kevin Li, Derek H Liu, Tran Bao Locke, Chih-Feng Lin, Chadi Makary, Alice Ottavi, Peter Papagiannopoulos, James N Palmer, Charles C L Tong, Bobby A Tajudeen, Sanjena Venkatesh, Kimberly Wei, Frederick Yoo, Alison J Yu, Jun Jin, Alberto M Saibene, John R Craig

Faculty, Staff and Students Publications

Objectives: While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS.

Methods: A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non-FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Na-Gst-1 Adsorbed On Alhydrogel Co-Administered With Different Toll-Like Receptor Agonists In Hookworm-Naive Adults Using A Controlled Human Infection Model In The Usa: A Phase 2, Double-Blind, Randomised Controlled Trial, Caroline K Dirosato, Elissa M Malkin, Sean M Lee, Guacyara Erwin, Lara Hoeweler, Larissa Scholte, Maria Elena Bottazzi, David I Pritchard, Peter J Hotez, Jeffrey M Bethony, David J Diemert

Faculty, Staff and Students Publications

Background: Necator americanus glutathione S-transferase-1 (Na-GST-1) performs a crucial enzymatic step in hookworm blood feeding and is a leading target for vaccine development. Phase 1 trials in Brazil, Gabon, and the USA of recombinant Na-GST-1 adsorbed on Alhydrogel (Na-GST-1/Al), co-administered with or without AP 10-701 (Toll-like receptor [TLR] 4 agonist) or CpG 10104 (TLR9 agonist), showed the vaccine was well tolerated, safe, and immunogenic. A controlled human hookworm infection (CHHI) model was previously developed to evaluate the effect of candidate hookworm vaccines on infection. We aimed to assess the effect of vaccination with three different Na-GST-1 vaccine formulations on subsequent …

Ebneo Commentary: The Lakana Trial: Mass Administration Of Azithromycin To Infants In Mali Did Not Reduce Mortality, Maya I Brasher, Monika S Patil

Faculty, Staff and Students Publications

The LAKANA trial: a randomized control trial evaluating the impact of mass administration of azithromycin to infants 1 to 11 months of age in Mali showed no reduction in mortality.

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …

Crispr/Cas9-Based Genome Editing: Understanding Differences In Dna Repair Pathways, Profiles, And Outcomes, Samuel Effah, Shirley Barrera, Nahia Urturi Ortiz, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the …

Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …

Hiv-1 Tat-Driven Glutamate Dysregulation: Implications For Cognitive Impairment In Hand, Brenna Duffy, Michael Nonnemacher, Sandhya Kortagere

Kimmel Cancer Center Faculty Papers

PURPOSE OF REVIEW: HIV-1-associated neurocognitive disorders (HAND) manifest in 15% to 50% of people with HIV, impairing learning and memory and executive function. The chronic generation of HIV-1 Transactivator of transcription (Tat) likely contributes to HAND via direct neuronal toxicity and glial-mediated toxicity. This review summarizes our current understanding of how chronic Tat generation from microglia and astrocytes promote glutamate excitotoxicity.

RECENT FINDINGS: In recent years, the indirect effects of Tat through the activation of glial cells have gained significant interest. This review highlights microglia and astrocytes as HIV-1 reservoirs that release Tat protein in the central nervous system. Specific …

Identifying Social Determinants Of Health Subgroups And Their Associations With Health Outcomes In A Prospective Us Adult Covid-19 Cohort: An Analysis Of The Inspire Registry, Yohali Burrola-Mendez, Eugene Lin, Canada Parrish, Chialing Hsu, Mandy J. Hill, Michael Gottlieb, Kristin L. Rising, Lauren E. Wisk, Nicole L. Gentile, Rachel E. Geyer, Robert A. Weinstein, Michelle Santangelo, Kristyn Gatling, Jonathan W. Dyal, Joann G. Elmore, Robert M. Rodriguez, Phillip Watts, Ji Chen, Zihan Diao, Erica S. Spatz, Kwun Cg Chan, K A. Stephens, Kelli N. O'Laughlin, Inspire Group

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

DESIGN: Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

SETTING: Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and …

Impact Of Dolutegravir-Based Regimens On Patient Satisfaction And Quality Of Life Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Christabel Ogechukwu Okoye, Ruth Jeminiwa, Ifeanyi Kanayo Ifeorah, Lotanna Ezeja, Yusuf Dauran, Sahabi Musa, Silas Usen Joel, Abdurrahman Murtala Bello, Amauche Pearl Ngige, Gabriel Ezenri, Abdulmuminu Isah, Ifunanya Ikhile, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

Background: Despite the global scale up of dolutegravir (DTG)-based regimens as the preferred first-line therapy for persons living with HIV (PLHIV), no comprehensive evidence exists on its effect on patient-reported outcomes such as Quality of Life (QoL) and patient satisfaction (PS). We conducted a systematic review and meta-analysis to provide the first comprehensive quantitative synthesis of the effect of DTG-based regimens on QoL and PS among PLHIV.

Method: We conducted literature search on PubMed, Scopus, Embase and Cochrane Library databases for peer-reviewed, primary studies published from January 2015 to January 2025. Studies using validated tools to evaluate QoL and PS …

Optimizing The Sensitivity Of Detection Of Respiratory Syncytial Virus Infections In Longitudinal Studies Using The Combination Of Weekly Sample Testing And Biannual Serology., Shannon C. Conrey, Daniel C. Payne, Maria Deza Leon, Monica Epperson, Melissa M. Coughlin, Allison R. Burrell, Claire P. Mattison, Rachel M. Burke, Julia M. Baker, Natalie J. Thornburg, Meredith L. Mcmorrow, Mary Allen Staat, Ardythe L. Morrow

Manuscripts, Articles, Book Chapters and Other Papers

Cohort studies are often challenged by incomplete adherence to sampling regimens, limiting the full capture of disease burden. We describe the detection of respiratory syncytial virus (RSV) infections achieved in a birth cohort using a combination of weekly nasal sample testing and serology. The Pediatric Respiratory and Enteric Viral Acquisition and Immunogenesis Longitudinal Cohort followed 245 maternal-child dyads from birth to age 18 to 24 months. Weekly mid-turbinate nasal swabs were tested for RSV using real-time polymerase chain reaction (RT-qPCR). Serum was tested for RSV pre-fusion F IgG and IgA antibody at age 6 weeks and biannually from 6 to …

The Relationship Between Psychological Stress And Sars-Cov-2 Nucleocapsid-Antibody Response Following Natural Infection: Longitudinal Findings From The Aegis Study, Erika T Beidelman, Ashley Judge, David B Allison, Stephanie Dickinson, Lilian Golzarri Arroyo, Anna L M Macagno, Michael J Ricciardi, Jon Macy, Stanley Perlman, Christina Ludema, Kevin C Maki, Molly Rosenberg

Faculty, Staff and Students Publications

Psychological stress can cause diminished immune response to infectious challenges. The extent this holds true during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the modifying effect of vaccination status is untested. We explored these relationships in a non-random sample standardized to the US adult population. Across 2178 participants in the Aegis study (2021-2022), we identified 507 eligible laboratory-confirmed SARS-CoV-2 infections. We estimated the natural log of nucleocapsid-binding antibody absorbance (N-antibody) at study visits up to 225 days following a positive SARS-CoV-2 test. Linear mixed effects models were fit to estimate the association of baseline perceived stress and, separately, …

Nmda Receptor Subunit Nmr-2 Regulates Pathogen-Induced Immune Responses Via The Nervous System In C. Elegans, Benson Otarigho, Jonathan Lalsiamthara, Alejandro Aballay

Faculty, Staff and Student Publications

Neural control of innate immunity must balance restraint of basal immune activity with rapid activation upon pathogen encounter. Glutamate, the primary excitatory neurotransmitter in the nervous system, has been implicated in several neurological disorders associated with inflammation, suggesting a potential link to immune regulation. However, how glutamatergic signaling contributes to immune balance remains unknown. Here, we demonstrated that the NMDA-type ionotropic glutamate receptor subunit NMR-2, a component of the NMDA receptor complex, acts in the

Polygenic Risk Scores And Hla Class Ii Variants Are Biomarkers Of Corticosteroid Response In Childhood Nephrotic Syndrome., Tiffany Tu, Alejandro Ochoa, Amika Sood, Ashley Dabrik, Megan Chryst-Stangl, Brandon Lane, Guanghong Wu, Frank Donovan, Ursula Harper, Settara Chandrasekharappa, Christopher Esezobor, Adaobi Solarin, David Hooper, Christine Sethna, Sandra Amaral, Mahmoud Kallash, Michelle Rheault, Priya Verghese, Vikas Dharnidharka, Eloise Salmon, Patricia Weng, Tarak Srivastava, Michael E Seifert, Cozumel Pruette, David Selewski, Keisha Gibson, Tracy Hunley, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arvind Bagga, Aditi Sinha, Nicholas Webb, Larry Greenbaum, Ali Gharavi, Krzysztof Kiryluk, Matthias Kretzler, Lisa Guay-Woodford, Simone Sanna-Cherchi, Agnieszka Bierzynska, Ania Koziell, Gavin Welsh, Moin Saleem, Charles Rotimi, Eileen Chambers, Cliburn Chan, Curegn Consortium, Pnrc Glomerular Disease Group, Cibmtr/Nmdp Consortium, Annette Jackson, Adebowale Adeyemo, Rasheed Gbadegesin

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are no current reliable predictors of therapy response at initial clinical presentation.

METHODS: To evaluate predictors, we conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 children (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched control individuals.

RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were …

Chronic Conditions And Mortality In Medicare Beneficiaries Before And After The Covid-19 Pandemic, R J Waken, Fengxian Wang, Jose F Figueroa, Rishi K Wadhera, Khavya Avula, E John Orav, Anne Mobley Butler, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: There were well-documented changes in health care use during the COVID-19 pandemic. Little is known about whether there were any associated decreases in claims-based comorbidity ascertainment that might have relevance to health services and policy research.

OBJECTIVE: To quantify differences in claims-based comorbidity assessment in Medicare beneficiaries pre- vs post-COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the 30 Chronic Conditions Warehouse 1- or 2-year lookback claims algorithms to ascertain each comorbidity with exact date ranges for all fee-for-service (FFS) and Medicare Advantage (MA) beneficiaries. Data were analyzed from April 2025 to April 2026.

EXPOSURES: The …

Association Of Infection Frequency And Incident Clonal Hematopoiesis Of Indeterminant Potential, Ajibike Lapite, Vernon A Burk, James Decuir, Junichi Ishigami, Seyedmohammad Saadatagah, Pradeep Natarajan, Christie M Ballantyne, Elizabeth A Platz, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis of indeterminant potential (CHIP) is an age-related phenomenon associated with increased risk of hematologic malignancy. Preclinical studies have shown that infection is a driver of CHIP; clinical studies in people living with HIV suggest a relationship between chronic infection and CHIP, but the association between infection frequency and incident CHIP in the general population remains unknown. We leveraged the atherosclerosis risk in communities study to design a closed prospective cohort study. CHIP was determined based on whole-exome sequencing at 2 time points 20 years apart. Included were 3,367 individuals without cancer or CHIP at time 1 and without …

Malaria In Children At 9 Us Hospitals: 2016-2023, Sesh Alexander Sundararaman, Brianne Roper, Amy K F Davis, Karen L Hanze Villavicencio, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Ziyi Wang, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Objectives: This study set out to describe imported pediatric malaria in the United States over an 8-year period, including patient demographics, clinical outcomes, and risk factors for severe disease.

Methods: A retrospective descriptive study of pediatric patients treated for malaria at 9 hospitals in the United States from 2016 to 2023 was conducted to analyze patient demographics, clinical outcomes, and risk factors for severe malaria.

Results: A total of 171 children were treated across the 9 US hospitals included in this study from 2016 to 2023. Most patients had traveled to West Africa to visit friends and relatives. Fever was …

Role Of Households With Children In Community Spread Of Multidrug-Resistant Enterobacterales, St. Louis, Missouri, Usa, Barrett Breeze, Ahmed Babiker, Sreenivas Konda, Alaina L Robinson, Stefan J Green, Catherine C Babbs, Federico Cunha, Katherine Y Shen, India Shepherd Hammond, Stephanie A Fritz, Latania K Logan

2020-Current year OA Pubs

Community-acquired multidrug-resistant (MDR) Enterobacterales bacteria are an increasing public health concern, yet whether households play a role in community spread remains unclear. We investigated 150 households with children in St. Louis, Missouri, USA, for MDR Enterobacterales. We cultured swab specimens from household members and environmental surfaces for identification and antimicrobial susceptibility testing. We also performed whole-genome sequencing in the 53 (35%) households where >1 MDR Enterobacterales species were recovered. Enterobacter hormaechei predominated, followed by Klebsiella pneumoniae and Pantoea species. Whole-genome sequencing revealed closely related strains shared between persons and environmental surfaces, suggesting potential intra-household transmission. We identified >1 horizontal gene …

Pneumomlpred: Innovating Pneumonia Management With Guideline Adherence Review And Explainable Machine Learning-Based Mortality Prediction - A Single-Centre Retrospective Study, Kamel A. Samara, Hiba Jawdat Barqawi, Saryia Adra, Batool Aldaher, Drishti D. Kampani, Enad Haddad, Hebah Soudan, Islam Ibrahim Anwar, Mohamad Besher Adi, Omar Hamadi, Yumna Almour, Mohamed Nassef, Zaher Al Aghbari, Eman Abu-Gharbieh

Abington Jefferson Health Papers

Introduction: Community-acquired pneumonia (CAP) is one of the leading causes of death globally. Changing antibiotic resistance profiles, paucity of reliable CAP mortality prediction models, and ageing populations will increase its burden. This study aims to evaluate adherence to CAP management guidelines as well as develop an ML-based mortality prediction model.

Methods: This retrospective, chart review included all CAP cases between 2016 and 2021. Variables collected included patients' demographics, comorbidities, vitals, laboratory, imaging, and culture findings, as well as initial and targeted antibiotic regimens. Data was pre-processed and analysed in python-3. Adherence to the American thoracic society/infectious diseases society of America …

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …

A Survey Of Health Professions Learners’ Attitudes Towards Social Media In Medical Education: A Substance Use Disorders Education Case Study, Gregory A. Jaffe, Sarah Lawson, William Leach, Mallika Kodavatiganti, Erin Avanzato, Katherine Fesperman, Heather Klusaritz

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Social media is a ubiquitous part of the modern world and plays a key role in the dissemination of information. While utilizing social media for educational purposes has been repeatedly demonstrated as feasible, it has been underutilized in medical education and remains a critical opportunity to integrate microlearning and stigma reduction curricula.

METHODS: A cross-sectional survey on social media usage, attitudes, and beliefs was sent to medical and nursing students at two large academic institutions within Philadelphia. Descriptive statistics are reported, and non-parametric tests were utilized for exploratory analyses.

RESULTS: Health learners were low consumers of social media, reporting …

Tunable Tripcides Suppress Virulence Factor Secretion During Staphylococcus Aureus Infection And Kill Dormant Cells, Hasan Tükenmez, Taylor M Nye, Suzanne Hickerson, Chloe L P Obernuefemann, Jerome S Pinkner, Karen W Dodson, Michael G Caparon, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Antimicrobial resistance (AMR) in common bacterial pathogens, including methicillin-resistant

+Cd49a+Cd103+ Cytotoxic Tissue-Resident Natural Killer Cells Infiltrate And Control Solid Epithelial Tumor Growth In Mice, Nina B Horowitz, Jennifer A Foltz, Et Al.

2020-Current year OA Pubs

Human tissue-resident natural killer (NK) cells (trNK cells), broadly defined by markers of tissue residency, such as CD49a [

Randomised Controlled Trial Comparing Antibiotic Cement Bead Pouch Versus Negative Pressure Wound Therapy For The Management Of Severe Open Tibia Fracture Wounds: Beads Versus Vac (Bvv) Protocol, Lucas S Marchand, Gerard Slobogean, Nathan N O'Hara, Anthony D Harris, David W Grainger, Lehana Thabane, Mohit Bhandari, Gregory J Della Rocca, Patrick J Kellam, Robert D Zura, Debra Marvel, Jeffrey L Wells, I Leah Gitajn, Kyle J Jeray, Robert V O'Toole, Zachary M Working, Roman M Natoli, Patrick F Bergin, Jennifer E Hagen, Ashley E Levack, Ernesto Guerra-Farfan, Gregory M Schrank, Joan N Hebden, Franca Mossuto, Cassandra Tsoutsounakis, David Pogorzelski, Hailey Pineda, Sofia Bzovsky, Sheila Sprague, Bvv Investigators

Faculty, Staff and Student Publications

Introduction: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis: …

Clinical And Demographic Characteristics Of Hospitalized Patients With Xylazine-Related Wounds, Elizabeth Novick, Nikhil Seval, Dagan Coppock, Mollie Tucker, Daniel Taupin, John Zurlo, Carolyn Kramer

Department of Medicine Faculty Papers

OBJECTIVES: Little is known about the demographic and clinical features of patients with xylazine-related wounds. We sought to characterize hospitalized patients with substance use disorder (SUD) and xylazine-related wounds seen for infectious diseases consultation.

METHODS: We retrospectively reviewed the medical records of 193 patients diagnosed with SUD at 3 Philadelphia hospitals between October 2023 and January 2024. Patients were identified as either being diagnosed with (n=73) or without (n=120) xylazine-related wounds. We compared the demographic and clinical features between the 2 groups.

RESULTS: Patients diagnosed with wounds were younger ( P < 0.001), more likely to be White or Hispanic and less likely to be Black/AA ( P < 0.001), more likely to have tested positive for fentanyl ( P < 0.001), amphetamines ( P < 0.001), and cocaine ( P 0.001), more likely to acknowledge injection ( P < 0.001), and more likely to leave the hospital by patient-directed discharge (PDD) ( P < 0.001). Most patients had multiple wounds (75%), and more than half (53%) had at least one wound greater than 10 cm at its widest dimension. Although most patients diagnosed with wounds received antibiotics, many did not have symptoms or signs of infection.

CONCLUSIONS: Xylazine-related wounds are highly associated with illicitly manufactured …

Promises, Pitfalls, And Paths Forward For The Pediatric Research Equity Act., Alexa L. Pagano, Danielle J. Green, Jennifer Goldman, Anjali Deshmukh

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Since its enactment in 2003, the Pediatric Research Equity Act (PREA) has significantly increased the number of pediatric drug studies performed and expanded pediatric drug labeling. Despite these advancements, many drugs used in children still lack pediatric-specific US Food and Drug Administration (FDA) labeling, even when pediatric studies are required by law. Recent legislative changes strengthened the FDA's enforcement authority over PREA. As these changes are implemented, persistent gaps in pediatric drug development warrant examination. Addressing these gaps may help ensure that children are systematically included in clinical research and that medications used in children are supported by rigorous …

Natural Maternal Immunity Protects Neonates From Escherichia Coli Sepsis., Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, Sing Sing Way

Manuscripts, Articles, Book Chapters and Other Papers

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity …

An Integrated Framework For Early Detection And Transmissibility Assessment Of Emerging Variants In Wastewater, Xingwen Chen, Tin Phan, Wei Lin Lee, Katie Clark, Steven F Rhode, Samantha Brozak, Bruce Pell, Tsultrim Palden, Mats Leifels, Anna Gitter, Yang Kuang, Stefan Wuertz, Janelle Thompson, Kristina D Mena, Eric J Alm, Fuqing Wu

Faculty, Staff and Student Publications

Tracking the emergence of new viral variants is critical for epidemic preparedness, but remains challenging because variants typically circulate at low prevalence during the early phase of outbreaks. Here, we present an integrated framework that combines sensitive variant detection in wastewater with quantitative assessment of transmissibility through dynamic epidemic modeling. Using the SARS-CoV-2 Omicron variant as a proof of concept, we developed a novel nested allele-specific RT-qPCR assay (NAS-PCR) that achieved a thousand-fold increase in sensitivity compared with allele-specific RT-qPCR (limit of detection: 0.5 copies/μl). NAS-PCR detected Omicron in wastewater samples from the Greater Boston area starting in September 2021, …

Long Covid Persistence And Surveillance Gaps Across 58 Us Hospitals, Jiazi Tian, Alaleh Azhir, Matthew Decaro, Ngan Chau, Jonas Hügel, Michele Morris, Jingya Cheng, Pedram Fard, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Shyam Visweswaran, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

Importance: Surveillance of postacute sequelae of SARS-CoV-2 infection (PASC) depends on diagnostic coding systems that capture fewer than one-half of affected individuals, rendering millions invisible to health systems and policymakers.

Objective: To quantify the gap between true PASC burden and diagnostic code-based estimates, determine the proportion representing chronic disease, and characterize organ system heterogeneity and temporal trends across diverse populations.

Design, setting, and participants: This retrospective cohort study used electronic health record data from 58 hospitals and affiliated clinics in 4 US regions, from 2017 to 2025. Adults (aged ≥18 years) with laboratory-confirmed SARS-CoV-2 infection or a COVID-19 diagnosis code …