Medical Specialties Commons^™

Regional Variation Of Underlying Kidney Diseases In Children Undergoing Chronic Kidney Replacement Therapy Around The Globe., Dagmara Borzych-Dużałka, Marjolein Bonthuis, Uma Ali, Yok-Chin Yap, Michael Manno, Yihui Zhai, Reyner Loza, Seema Hashmi, Naye Choi, Kenza Soulami, Judith Exantus, Mohamed S. Al Riyami, Sameh Mabrouk, Marbella Ma Angeles, Cristina Zelaya-Camacho, Henny Adriani Puspitasari, Syed Saimul Huque, Francisco Cano, Kar Hui Ng, Sevcan A. Bakkaloğlu, Jerome Harambat, Kitty J. Jager, Bradley A. Warady, Franz Schaefer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is a scarcity of information regarding the distribution of the diseases leading to kidney failure (KF) in children living in the emerging world. We used registry data to provide a global overview of the underlying disease spectrum in children commencing kidney replacement therapy (KRT).

METHODS: We analyzed KF causes among 23,620 children and adolescents commencing maintenance KRT in 80 countries, using data from the IPNA Global KRT Registry (including ESPN/ERA Registry), the International Pediatric Dialysis Network (IPDN), the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The analysis considered …

High Concordance Of Physician-Attestation With Manual Data Abstraction For Sickle Cell Type: An Ash Rc Data Hub Study, Alexis Thompson, Ashima Singh, Donna Neuberg, Amanda Brandow, Allison King, Sophie Lanzkron, Emily Semmel, Sam Walters, Susan Rogers, Kathleen Torres, William Wood

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The American Society of Hematology Research Collaborative (ASH RC) has built an SCD Data Hub (DH) to facilitate research and quality improvement using real-world data. To our knowledge, we report here the first analyses from the DH, focusing on cohort demographics and accurate identification of SCD diagnosis type. DH sites have data use agreements with ASH RC to extract and transfer electronic health record (EHR) data at least quarterly. Principal investigators (PI) provided additional attestation of SCD diagnosis based on existing local data sources deemed …

High-Precision Automated Bone Age: A Clinically Useful Tool In Monitoring Of Treatment Effects In Children And Adolescents, Hans Henrik Thodberg, Lise Aksglaede, Anders Juul, Shanlee M. Davis, Judith L. Ross

Department of Pediatrics Faculty Papers

The clinical value of serial bone age (BA) determinations in children during growth is limited by the manual rater variability (precision 0.63 years). The objective of this work was to determine the precision of automated bone age and bone health index (BHI) measurements by BoneXpert and to establish the time interval at which the automated method can detect a significant treatment effect. The data were from a case-control trial (oxandrolone/placebo) following 90 boys with Klinefelter syndrome (KS) with five visits over 2 years, recording X-rays of both hands. The precision of BA was 0.08 years [0.07; 0.09] 95% CI, leading …

Out-Of-Pocket Costs And Antihypertensive Medication Use Among Veterans: A Natural Experiment, Alexander R. Zheutlin, Alexander Chaitoff, Daniel Addo, Joshua A. Jacobs, Catherine G. Derington, Eric L. Stulberg, Peter A. Glynn, Bernardo Modenesi, Jordana B. Cohen, Adam P. Bress

Department of Neurology Faculty Papers

BACKGROUND: Blood pressure (BP) control remains suboptimal in the United States despite available low-cost antihypertensive medications. Even small out-of-pocket medication costs may contribute to adherence. We determined whether $0 versus >$0 out-of-pocket costs for antihypertensive medications is associated with differences in adherence, discontinuation, BP control, and cardiovascular outcomes.

METHODS: We included veterans with newly diagnosed hypertension who initiated antihypertensive medication in the Veterans Health Administration from 2004 to 2022. A fuzzy regression discontinuity design with 2-stage residual inclusion leveraged differences in medication copay policy at a 50% service-connected disability threshold (≥50% service-connected disability: $0 out-of-pocket cost versus < 50%: $8 monthly cost). Outcomes included 1-year medication nonadherence (proportion of days covered < 80%), 1-year medication discontinuation (no medication in the final 90 days of the study year), 1-year BP control (systolic BP/diastolic BP < 140/90 mm Hg and < 130/80 mm Hg) and cardiovascular disease events (myocardial infarction, coronary revascularization, peripheral artery disease, or stroke).

RESULTS: Among 417 …

Ms-Gator: Multi-Scale Graph Attention With Topological Reasoning For Segmentation And Classification Of Prostate Cancer Based On Gleason Scores Using Histopathology Images, Sujata Patil, Mahadeva Swamy, Kavitha Sooda, Rajanikanth Vadigepalli, Khalid Nazim Abdul Sattar, Md Rafeeq

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prostate cancer is one of the prevalent and potentially fatal malignancies, affecting men globally. Accurate segmentation and classification of prostate cancer in histopathology images remain challenging due to complex tissue architecture, staining variability, and high inter-observer differences in manual diagnosis. To address these challenges, this research proposes a Multi-Scale Graph Attention with Topological Reasoning (MS-GATOR) for segmentation and classification of prostate cancer based on Gleason Scores (GS). The MS-GATOR incorporates topological reasoning with hierarchical biological structures by constructing a graph-based representation among three spatial scales such as nuclei, glands, and tissues using Delaunay triangulation to capture both geometric and photometric …

A Digital Diabetes Prevention Program For Hispanic Adolescents (Fit24+): Protocol For A Feasibility Randomized Controlled Trial, Erica G Soltero, Marbelly Partida, Sandra Mihail, Lizette Villanueva, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Maria J Redondo, Matthew Buman, Debbe Thompson

Faculty, Staff and Students Publications

Background: Hispanic youth are disproportionately impacted by obesity and subsequent type 2 diabetes (T2D) yet remain underrepresented in diabetes prevention research. Digital health interventions hold promise for increasing the accessibility to and engagement in disease prevention programming, particularly among high-risk populations. However, there is a significant gap in the literature regarding digital T2D prevention programs for adolescents or Hispanic youth.

Objective: The objective of this article is to describe the protocol for examining the feasibility of a 12-week digital diabetes prevention program among Hispanic adolescents with obesity.

Methods: Participants (N=40; aged 12-16 years) will be randomized (1:1) to a 12-week …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

Dasatinib And Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration In Sm/J Mice, Emanuel J. Novais, Olivia K. Ottone, Sanjana Jagannath, Esther Jesutofunmi Akande, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis …

Utility Of Right Ventricular Mass Ratios In Recipients With Pulmonary Hypertension: A United Network For Organ-Sharing Database Analysis, Matthew P. Weber, Danial Ahmad, Howard J. Eisen, Eugene Storozynsky, René J. Alvarez, J. Eduardo Rame, Keshava Rajagopal, John W. Entwistle, Charles Hoopes, Vakhtang Tchantchaleishvili

Division of Cardiology Faculty Papers

PURPOSE: There is a lack of data reviewing the role of predicted cardiac mass ratio (PCMR) in transplant recipients with pulmonary hypertension (PH). In particular, the right ventricular (RV) mass ratio (RVMR) is a component of PCMR not yet studied separately for this purpose. We aimed to review the relationship of PCMR and RVMR with PH in terms of post-transplant overall survival.

METHODS: The United Network for Organ-Sharing (UNOS) database was queried for primary heart transplant (HTx) patients from 2004 to 2023. Predicted RVMR was calculated for donors and recipients. A parsimonious multivariable model Cox model was formed for risk …

Cerebellar Oligodendrocytic Α-Synuclein Pathology And Dentate Nucleus Neuronal Hypertrophy In Parkinson’S Disease, Diego Iacono, Hui Peng, John Paul Bouffard, Roger Kurlan

Department of Neurology Faculty Papers

Idiopathic Parkinson's disease (iPD) research has historically prioritized basal ganglia dysfunction and neuronal Lewy body pathology, often overlooking cerebellar and non-neuronal cells contributions. This study investigates cerebellar neuropathology in iPD, specifically focusing on neuronal and non-neuronal cells of the dentate nucleus (DN) and its adjacent white matter (DN-WM). We systematically assessed autopsy-confirmed iPD brains vs. age-matched controls using immunohistochemistry and stereology-based morphometry methods. The study evaluated α-synuclein pathology, other common age-related co-occurring pathologies (β-amyloid, Tau, neuroinflammation), myelin integrity (Luxol-Fast-Blue), and neuronal volumetric changes in the DN of the cerebellum. In iPD brains, we identified intracytoplasmic α-synuclein inclusions within oligodendrocytes across …

Contraception In The Ed: Understanding Education And Opportunities For Clinicians To Advise Patients, Hannah B. Lewis, Teagan R. Mccarthy, Dara Kass, Jennifer L. Kahoud

Department of Emergency Medicine Faculty Papers

Introduction: The United States faces a high rate of unwanted pregnancies. Despite this, many people continue to face barriers to accessing contraception. The emergency department (ED) can help bridge these gaps, but emergency clinicians must first feel comfortable offering contraceptive services. In this study, we sought to determine emergency clinician comfort in prescribing contraceptives and educating patients on their use. We also gauged clinician interest in receiving education specifically geared toward contraceptive care.

Methods: We conducted an online survey of ED residents, attendings, and advanced practice clinicians at Thomas Jefferson Univerity Hospital and affiliates in both the urban and suburban …

A Prolonged Nightly Fasting Plus Telehealth Coaching Intervention (Pnf+) For Men On Androgen Deprivation Therapy For Pca: A Pilot Feasibility Randomized Controlled Trial, Kuang-Yi Wen, Julianne Freedman, Kevin K. Zarrabi, Rachel Slamon, Rita Smith, Jessica Liang, Patrick Mille, William J. Tester, William Kevin Kelly

Department of Medical Oncology Faculty Papers

Background/Objectives: This study aimed to assess the feasibility and acceptability of a 3-month health coaching intervention to promote PNF and healthy diet for men on ADT for PCa.

Methods: The study was carried out via a two-armed randomized controlled trial including 40 patients with PCa at a medical center in Philadelphia. During the 3-month period, the intervention group (PNF+) received health coaching utilizing an interactive text message system, and the control group received healthy eating text messages for the same duration. The outcome variables were feasibility and acceptability.

Results: The PNF+ group (n = 27) had high …

The Ki-67 Proliferation Index And Recurrence Risk Of Intracranial Meningioma: A Multicenter, Retrospective Cohort Study Of 5,050 Patients, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Pedro Góes, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

Purpose: The Ki-67 proliferation index (Ki-67 PI) has been associated with meningioma recurrence, yet its clinical utility remains debated. Whether Ki-67 PI provides prognostic information across subgroups defined by both WHO grade and extent of resection remains to be investigated.

Methods: We analyzed 5,050 patients with intracranial meningiomas from the international PERNS cohort (42 centers, diagnosed between 1989-2019) who underwent surgical resection without postoperative radiotherapy. Ki-67 PI prognostic accuracy was assessed up to 10 years postoperatively by using ROC analyses and estimating its association with the risk of recurrence.

Results: Results demonstrated that the prognostic value of Ki-67 PI differed …

Organ Procurement Organization Utilization Of Portable Hypothermic Oxygenated Machine Perfusion In Liver Transplantation: The First Us Experience, Christine E. Haugen, Muhammad Bilal Moeen-Ud-Din, Abdalla M. Hadhoud, Achintya Kaw, James R. Butler, James V. Guarrera, Sherry Quire, Ralph C. Quillin

Department of Surgery Faculty Papers

BACKGROUND: Advanced machine perfusion techniques have increased the use of hard-to-place organs, effectively changing the liver transplantation landscape. Liver transplantation machine perfusion has been driven largely by industry or individual transplant centers. We describe the implementation of a portable, organ procurement organization-initiated hypothermic oxygenated machine perfusion strategy for liver transplantation as a proof of concept.

METHODS: Surgeons and staff at a regional organ procurement organization (Indiana Donor Network) were trained to use and cannulate liver allografts using a portable hypothermic oxygenated machine perfusion platform. We evaluated all liver transplantations recovered and placed on hypothermic oxygenated machine perfusion (N = 18) …

The Integrated 31-Gene Expression Profile Test Identifies Low-Risk Patients With Cutaneous Melanoma Who Can Forego The Slnb Procedure: Results From A Prospective, Multicenter Trial., Timothy Beard, J Michael Guenther, Stanley P Leong, Maki Yamamoto, Samuel Dierks, Brenda Sickle-Santanello, Andrew Ward, Mark Cripe, Parth Shah, Shawn Young

Oncology Articles

AIMS: Prospectively confirm use of the integrated 31-gene expression profile test (i31-SLNB) in patients with cutaneous melanoma to predict sentinel lymph node biopsy (SLNB) positivity and assess recurrence rates in those considered low risk by i31-SLNB who did not have an SLNB.

METHODS: Patients with T1-T4 tumors being considered for SLNB who received 31-gene expression profile (31-GEP) testing in the multi-center, prospective DECIDE study were included (n = 912). Kaplan-Meier analysis was used to estimate recurrence-free survival (RFS).

RESULTS: Among 430 patients with T1-T4 tumors who had an SLNB, the positivity rate was 2.6% (3/114) in those with < 5% i31-SLNB-predicted risk versus 21.4% (28/131) in those with >10% predicted …

Aht Diagnoses: The Influences Of Clinical Presentation And Evidence Of Impact, Ruairi Smith-Dewey, Angela Bachim, Colleen Bressler, Kristine Campbell, Lori Frasier, Christopher Greeley, Danielle Horton, Nicole Johnson, Jan Leonard, Megan M Letson, Caitlin Mcnamara, Ashley Sherman, Shalon Nienow, Stuart Sommers, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Background: The frequency of abusive head trauma (AHT) diagnoses by child abuse pediatricians (CAPs), especially regarding external evidence of head impact, has been questioned.

Objectives: To compare CAP diagnoses in subjects with subdural hemorrhage (SDH) across clinical presentations, including subgroups with and without external evidence of head impact. Additionally, we aimed to describe subjects with SDH and concomitant suspicious injuries (CSI) without evidence of head impact.

Participants and setting: Multicenter retrospective study including subjects < 24 months old with SDH.

Methods: Subjects were divided into groups based on clinical presentations: Ill SDH only, Non-ill SDH only, and SDH + CSI. Groups were subcategorized based on presence/absence …

Yield Of Injury Testing For Contacts Of Children Evaluated For Physical Abuse, Lígia Batista, Joanne N Wood, Tagrid M Ruiz-Maldonado, M Katherine Henry, Jan Leonard, Angela Bachim, James D Anderst, Farah W Brink, Hannah B Sahud, Lori D Frasier, Nancy S Harper, Natalie Laub, Colleen J Bressler, Daniel M Lindberg

Faculty, Staff and Students Publications

Background: Siblings and household contacts of physically abused children are at increased risk for physical abuse and may have injuries that are not clinically apparent. However, injury testing recommendations for contact children remain debated.

Objective: Our objective was to describe testing practices and yield for contacts of physically abused children.

Participants and settings: This is a cross-sectional study of children < 10 years old evaluated for physical abuse at 10 US pediatric referral centers in the CAPNET research network.

Methods: We report the proportion of contact children who had a skeletal survey (SS) or neuroimaging and describe the proportion of tests that identified injuries.

Results: Among 6256 index evaluations, 4863 contacts were identified. Among 794 contacts with physical examinations, …

Fronto-Cerebellar Features Associate With Cognitive Dysfunction In Childhood-Onset Systemic Lupus Erythematosus, Hanne Van Der Heijden, Gabrielle Alonzi, Amanda Cao, Raquel Van Gool, Merve Koç Yekedüz, Lise Vrolix, Itamar Ronen, Vanessa Rameh, Kyle Mcbrearty, Aditi Deokar, Robert P Sundel, Eyal Muscal, Joseph Gonzalez-Heydrich, Andrea Knight, Joyce C Chang, Jaymin Upadhyay

Faculty, Staff and Students Publications

Objective: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Methods: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

Results: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients …

Trauma-Related Compulsions In Obsessive-Compulsive Disorder: Functional Insights From Factor Analysis, Caitlin M Pinciotti, Max Thorsson, Gregor Horvath, Matti Cervin

Faculty, Staff and Students Publications

Resisting obsessive-compulsive disorder (OCD) compulsions is a key predictor of exposure and response prevention (ERP) effectiveness, yet trauma-exposed individuals with OCD endorse more severe compulsions and are more likely to be labelled 'treatment resistant.' Among trauma-exposed individuals, compulsions are theorised to function to prevent future trauma and cope with trauma-related responses. Recent findings suggest that certain compulsions in the context of trauma exposure differentially impact treatment outcomes, yet missing from extant literature is a larger empirically derived conceptualisation for how trauma may impact the underlying function of compulsions. In a sample of 662 adult patients enroled in intensive OCD treatment …

Results Of A Randomized, Double-Masked, Placebo-Controlled Phase 1/2 Study Of A Trpv1 Antagonist Sjp-0132 In Participants With Dry Eye Disease, Tomoyuki Wada, Kazunori Omatsu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED).

Design: Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study.

Participants: Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones).

Methods: This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. …

Avacincaptad Pegol For Geographic Atrophy Secondary To Age-Related Macular Degeneration: Two-Year Efficacy And Safety Results From The Gather2 Phase 3 Trial, Arshad M Khanani, Carl J Danzig, Jeffrey S Heier, Glenn J Jaffe, Peter K Kaiser, David R Lally, Sunil S Patel, Lejla Vajzovic, Christina Y Weng, Hersh Patel, Julie Clark, Dhaval Desai, Don Luo, Erin Henry, Frank G Holz

Faculty, Staff and Students Publications

Purpose: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2 mg was investigated in GATHER2, with positive year 1 results published. Herein, 2-year results are reported.

Design: Phase 3, randomized, sham-controlled study (ClinicalTrials.gov identifier, NCT04435366).

Participants: Patients with non-center point-involving geographic atrophy (GA).

Methods: Eligible patients were randomized 1:1 to receive monthly ACP 2 mg (n = 225) or sham (n = 222) for 1 year. At month 12, patients who received ACP 2 mg were randomized again 1:1 to dosing every month (EM; n = 96) or every …

Empiric Azithromycin Alters The Upper Respiratory Microbiome And Resistome Without Anti-Inflammatory Benefit In Covid-19, Abigail Glascock, Cole Maguire, Hoang Van Phan, Emily C Lydon, Joanna Schaenman, Carolyn S Calfee, Esther Melamed, John Greenland, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Linda N Geng, Bali Pulendran, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, William B Messer, Mark M Davis, Kari C Nadeau, Monica Kraft, Christian Bime, David J Erle, Mark A Atkinson, Scott C Brakenridge, Lauren I R Ehrlich, Ruth R Montgomery, Albert C Shaw, Catherine L Hough, David A Hafler, Alison D Augustine, Patrice M Becker, Bjoern Peters, Al Ozonoff, Annmarie Hoch, Seunghee Kim-Schulze, Florian Krammer, Steven Bosinger, Walter Eckalbar, Matthew C Altman, Michael Wilson, Leying Guan, Holden Maecker, Hanno Steen, Impacc Network, Joann Diray-Arce, Nadine Rouphael, Steven H Kleinstein, Naresh Doni Jayavelu, Elaine F Reed, Ofer Levy, Victoria T Chu, Charles R Langelier

Faculty, Staff and Students Publications

Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized for COVID-19. We compared the upper respiratory microbiome, resistome and systemic immune response in patients treated with azithromycin (n = 366) with those who received no antibiotics (n = 474) or other antibiotics (n = 324). We found that azithromycin altered microbiome composition and increased the expression …

Feasibility Of A Large Language Model Chatbot To Support Parental Understanding In The Picu, R Brandon Hunter, Satid Thammasitboon, Sreya Rahman, Sriya Kakarla, Pamela Petersen, Shelley Kumar, Thomas Rappold, Sanjiv Mehta

Faculty, Staff and Students Publications

Objectives: To evaluate the feasibility of a large language model (LLM)-based chatbot for answering parental questions in the PICU and inform design of a randomized controlled trial (RCT).

Design: Prospective single-arm feasibility study conducted from August 2024 to December 2024.

Setting: Quaternary PICU.

Subjects: Fourteen parents of children admitted to the PICU.

Interventions: Parents engaged in 10-minute sessions with a HIPAA-compliant GPT-4o- (Generative Pretrained Transformer 4o, OpenAI, San Francisco, CA) based chatbot prompted with patient-specific electronic health record (EHR) data.

Measurements and main results: Feasibility was assessed through four criteria: parental engagement and satisfaction, provider perceptions, accuracy and safety, and …

Body Mass Index And Survival In Children Receiving Extracorporeal Membrane Oxygenation, Pilar Anton-Martin, Keith Baxelbaum, Shilpa Vellore, Erika O'Neil, Vinai Modem, Sameer Thadani

Faculty, Staff and Students Publications

Importance: Underweight and obesity represent opposite ends of the nutritional risk spectrum that negatively affect children's health worldwide. Both conditions have been associated with increased mortality in pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support.

Objective: To investigate the association of underweight and obesity status with pediatric ECMO outcomes using body mass index (BMI) z scores.

Design, setting, and participants: This retrospective cohort analysis used data from the Extracorporeal Life Support Organization (ELSO) database from January 1, 2019, to December 31, 2023. Participants included all pediatric patients from international ECMO centers aged 29 days to 18 years who received ECMO …

Development And Internal Validation Of A Pretransplant Biomarker Panel For Mortality Prediction Following Liver Transplant, Guergana G Panayotova, Sopio Simonishvili, Lianhua Jin, Duc T Nguyen, Edward A Graviss, Yong Qin, Anastasia Xynogala, Tumininu Ayorinde, Laurie J Minze, Alexander Lemenze, Krupa R Mysore, Julie M Corkrean, Linda W Moore, Flavio Paterno, Ashish Saharia, Constance M Mobley, Arpit Amin, Mark J Hobeika, Xian C Li, Paul J Gaglio, R Mark Ghobrial, James V Guarrera, Keri E Lunsford

Faculty, Staff and Students Publications

Importance: Current pretransplant clinical scoring systems fail to accurately estimate post-liver transplant (LT) survival, making recipient selection challenging. Persistent immune dysfunction contributes to early LT recipient mortality but is not captured by existing models.

Objective: To identify plasma biomarkers of pretransplant immune dysfunction and to develop a biomarker-based pre-LT risk stratification tool to predict post-LT mortality.

Design, setting, and participants: Prospective biomarker analysis of consecutively enrolled adult LT recipients was conducted. Healthy controls were included for baseline comparison. Patients undergoing LT at Houston Methodist Hospital (October 1, 2013, to December 31, 2017) and Rutgers/University Hospital (January 1, 2019, to March …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Confessions In Cases Of Child Physical Abuse-A Capnet Study, Margaret R Russell, Antoinette L Laskey, Henry T Puls, Suzanne P Starling, Joanne N Wood, Daniel M Lindberg, Nancy S Harper, Caitlin R Mcnamara, Angela N Bachim, Farah W Brink, Lori D Frasier, James D Anderst, Porcia Vaughn, Kristine A Campbell

Faculty, Staff and Students Publications

Objective: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

Methods: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

Results: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

Conclusions: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Confessions In Cases Of Child Physical Abuse-A Capnet Study., Margaret R. Russell, Antoinette L. Laskey, Henry T. Puls, Suzanne P. Starling, Joanne N. Wood, Daniel M. Lindberg, Nancy S. Harper, Caitlin R. Mcnamara, Angela W. Bachim, Farah W. Brink, Lori D. Frasier, James Anderst, Porcia Vaughn, Kristine A. Campbell

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prior research on confessions of physical abuse (PA) has explored mechanisms of injury. Little is known about conditions supporting a confession of abuse or how confessions may influence case outcomes.

METHODS: This cross-sectional study of suspected PA in children aged < 10 years at 10 centers participating in CAPNET, a multicenter child PA research network, included children with in-person Child Abuse Pediatrics (CAP) consultations between February 2021 and December 2022 and excluded children without injury. Our focus was a confession of inflicted injury known to the CAP during clinical involvement. We compared child and clinical characteristics, out-of-home (OOH) placements, and arrests between cases with and without confessions. Multivariable models using generalized estimating equations (GEE) produced adjusted predicted probabilities (APP) clustering by CAPNET site.

RESULTS: Confessions were known to CAPs in 115/4297 (2.7%) cases, with significant site variability. In a multivariable GEE model, confessions were more likely in cases with injuries with high specificity for abuse (APP 6.0% vs 1.6%, P < .001), near-fatality (APP 5.6% vs 2.3%, P < .001), and older children (APP 4.8% vs 2.5%, P = .025). OOH placements and arrests were more common in cases with confessions. CAP awareness of confessions, OOH placements, and arrests did not follow racial or ethnic patterns seen in the US child welfare system. Lower socioeconomic status was associated with OOH placements and arrests but not with CAP awareness of confessions.

CONCLUSIONS: Our findings highlight differences in case characteristics and outcomes where a confession is known to the CAP and raise questions about …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …