Medicine and Health Sciences Commons^™

Associations Between Epilepsy, Respiratory Impairment, And Minor Ecg Abnormalities In Children, See Wai Chan, Angela Chun, Linh Nguyen, Beth Bubolz, Anne E Anderson, Yi-Chen Lai

Faculty, Staff and Students Publications

Objective: We sought to examine the effects of acute seizures and respiratory derangement on the cardiac electrical properties reflected on the electrocardiogram (ECG); and to analyze their potential interactions with a diagnosis of epilepsy in children.

Methods: Emergency center (EC) visits with seizure or epilepsy diagnostic codes from 1/2011-12/2013 were included if they had ECG within 24 h of EC visit. Patients were excluded if they had pre-existing cardiac conditions, ion channelopathy, or were taking specific cardiac medications. Control subjects were 1:1 age and gender matched. Abnormal ECG was defined as changes in rhythm, PR, QRS, or corrected QT intervals; …

Yield Of Skeletal Surveys In National Network Of Child Abuse Pediatricians: Age Is Key, Caitlin R Mcnamara, Joanne N Wood, Daniel Lindberg, Kristine A Campbell, Spencer Poston, Matthew Valente, Maria Antonucci, Jennifer Wolford, Carmen Coombs, Hannah Sahud, Jennifer Clarke, Farah W Brink, Angela Bachim, Lori D Frasier, Nancy S Harper, John D Melville, Natalie Laub, James Anderst, Rachel P Berger

Faculty, Staff and Students Publications

Background: Skeletal surveys (SS) are recommended for the evaluation of suspected physical abuse in children < 2 years old. No guidelines exist for SS completion in children between 2 and 5 years old.

Objective: To determine rates of SS completion by age and examine variables associated with occult fracture identification in older children.

Participants and setting: Observational cross-sectional multi-center study of 10 US pediatric centers 2/2021-9/2022 including children < 6 years old evaluated for physical child abuse.

Methods: The principal outcome is occult fracture identified on SS. Non-parametric tests were conducted from comparison between age groups and those with and without occult fractures.

Results: The rate of SS completion declined with increasing age from a high of 91 % in infants < 6 months old to 7 % in children 5-5.9 years old. The proportion of SS with occult fractures also decreased with age. Of 450 children 2-5 years old with a SS, 20 [4 % (95 % CI: 3-8 %)] had an occult fracture. The rate of occult fractures among children 2-5 years old who were diagnosed with abuse and not admitted to the hospital was 0.3 % (95 % CI 0-0.6 %)]. Over 30 % of children 2-5 years old were diagnosed with child abuse by a child abuse pediatrician without completion of a SS.

Conclusion: In children 2-5 years of …

Perivascular Epithelioid Cell-Family Tumors In Children, Adolescents, And Young Adults: Clinicopathologic Features In 70 Cases, Phoebe M Hammer, Angus Toland, Muhammad Shaheen, Archana Shenoy, Ashwini Esnakula, M John Hicks, Mikako Warran, Alyaa Al-Ibraheemi, Jessica L Davis, Serena Y Tan

Faculty, Staff and Students Publications

Context.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.

Objective.—: To describe a multi-institutional series of PEComas in children, adolescents, and young adults.

Design.—: PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and the authors' files.

Results.—: Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominantly in the kidney (53 of 70), followed by the …

Identification Of Single-Cell Blasts In Pediatric Acute Myeloid Leukemia Using An Autoencoder, Alice Driessen, Susanne Unger, An-Phi Nguyen, Rhonda E Ries, Soheil Meshinchi, Stefanie Kreutmair, Chiara Alberti, Pavel Sumazin, Richard Aplenc, Michele S Redell, Burkhard Becher, María Rodríguez Martínez

Faculty, Staff and Students Publications

Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell …

Secondary Acmg And Non-Acmg Genetic Findings In A Multiethnic Cohort Of 16,713 Pediatric Participants, Amir Hossein Saeidian, Michael E March, Leila Youssefian, Deborah J Watson, Esha Bhandari, Xiang Wang, Xiaonan Zhao, Nichole Marie Owen, Alanna Strong, Margaret H Harr, Elizabeth Bhoj, Elaine Zackai, Hassan Vahidnezhad, Johann E Gudjonsson, Stephen D Cederbaum, Joshua L Deignan, Joseph Glessner, Wayne W Grody, Hakon Hakonarson

Faculty, Staff and Students Publications

Purpose: Clinical next-generation sequencing is an effective approach for identifying pathogenic sequence variants that are medically actionable for participants and families but are not associated with the participant's primary diagnosis. These variants are called secondary findings (SFs). According to the literature, there is no report of the types and frequencies of SFs in a large pediatric cohort that includes substantial African-American participants. We sought to investigate the types (including American College of Medical Genetics and Genomics [ACMG] and non-ACMG-recommended gene lists), frequencies, and rates of SFs, as well as the effects of SF disclosure on the participants and families of …

Family Lore, A Variant Of Uncertain Significance, And Cadasil, Rhys Duarte, Liesbeth Vossaert, Sandra A Darilek, Chelsi Rose, Evan Schauer, Christian Parobek, Emily Bland, Keren Machol, Elizabeth Mizerik, Chaya N Murali

Faculty, Staff and Students Publications

An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in NOTCH3, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his …

Residential Proximity To Oil And Gas Developments And Childhood Cancer Survival, Thanh T Hoang, Rutu A Rathod, Omar Rosales, Maria I Castellanos, Jeremy M Schraw, Elyse Burgess, Erin C Peckham-Gregory, Abiodun O Oluyomi, Michael E Scheurer, Amy E Hughes, Philip J Lupo

Faculty, Staff and Students Publications

Background: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers.

Methods: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or …

Antiseizure Medication-Induced Hypersensitivity Reactions: Data From A Large Healthcare System, Benjamin Cadle, Feride Un Candan, Zulfi Haneef, Christopher Ryan Barton, Dylan Brock, Irfan Ali, Jaime Shoup, Cemal Karakas

Faculty, Staff and Students Publications

Background and objectives: Data on hypersensitivity reactions (HR) to individual anti-seizure medications (ASMs), and reactions to additional ASMs, is often limited by sample size. This data is vital in helping clinicians identify initial and subsequent ASMs to use in treating persons with epilepsy (PWE). Using a very large dataset, our study attempts to quantify the occurrence of HR across 31 different ASMs. We also attempt to investigate whether certain pairs of ASMs are associated with a higher frequency of HR.

Methods: The Slicer-Dicer tool in the Epic electronic medical records system was used to analyze patients seen between 2012 and …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Heena Patel, Siddharth Srivastava, Lindsay C Swanson, Boris Keren, Sandra Whalen, Cyril Mignot, Xiaodong Wang, Qian Chen, Jill A Rosenfeld, Scott Mclean, Rebecca O Littlejohn, Undiagnosed Diseases Network, Lisa Emrick, Lindsay C Burrage, Ruben Attali, Gaetan Lesca, Cecile Acquaviva-Bourdain, Catherine Sarret, Laurie H Seaver, Konrad Platzer, Tobias Bartolomaeus, Cornelia Wünsch, Susann Fischer, Ana Maria Rodriguez Barreto, Jorge L Granadillo, Elisabeth Schreiner, Theresa Brunet, Ulrich A Schatz, Isabelle Thiffault, Sureni V Mullegama, Jacques L Michaud, Fadi F Hamdan, Elsa Rossignol, Philippe M Campeau

Faculty, Staff and Students Publications

Background: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

Methods: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

Results: We reinforce the …

Seasons Of Kawasaki Disease During The Covid-19 Pandemic., Todd T. Nowlen, Ashraf S. Harahsheh, Geetha Raghuveer, Simon Lee, Anji T. Yetman, Nagib Dahdah, Michael A. Portman, Supriya S. Jain, Michael Khoury, Selemet Tierney, Cedric Manlhiot, Pedrom Farid, Brian W. Mccrindle

Manuscripts, Articles, Book Chapters and Other Papers

The incidence of Kawasaki Disease has a peak in the winter months with a trough in late summer/early fall. Environmental/exposure factors have been associated with a time-varying incidence. These factors were altered during the COVID-19 pandemic. The study was performed through the International Kawasaki Disease Registry. Data from patients diagnosed with acute Kawasaki Disease and Multiple Inflammatory Syndrome-Children were obtained. Guideline case definitions were used to confirm site diagnosis. Enrollment was from 1/2020 to 7/2023. The number of patients was plotted over time. The patients/month were tabulated for the anticipated peak Kawasaki Disease season (December-April) and non-peak season (May-November). Data …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Comparing Methods For Risk Prediction Of Multicategory Outcomes: Dichotomized Logistic Regression Vs. Multinomial Logit Regression, Lei Li, Matthew A Rysavy, Georgiy Bobashev, Abhik Das

Faculty, Staff and Student Publications

Background: Medical outcomes of interest to clinicians may have multiple categories. Researchers face several options for risk prediction of such outcomes, including dichotomized logistic regression and multinomial logit regression modeling. We aimed to compare these methods and provide guidance needed for practice.

Methods: We described dichotomized logistic regression, multinomial continuation-ratio logit regression, which is an alternative to standard multinomial logit regression for ordinal outcomes, and logistic competing risks regression. We then applied these methods to develop prediction models of survival and neurodevelopmental outcomes based on the NICHD Extremely Preterm Birth Outcome Tool model. The statistical and practical advantages and flaws …

Longitudinal Assessment Of Retinopathy Of Prematurity (Longrop) Study: Impacts Of Viewing Time And Ability To Compare On Detection Of Change, Tatiana R. Rosenblatt, Hashem H. Ghoraba, Marco H. Ji, Caroline R. Baumal, Audina M. Berrocal, Cagri G. Besirli, Kimberly A. Drenser, Anna L. Ells, C. Armitage Harper, G. Baker Hubbard, Eric D. Nudleman, Polly A. Quiram, Irena Tsui, Yoshihiro Yonekawa, Edward H. Wood, Jochen Kumm, Darius M. Moshfeghi

Wills Eye Hospital Papers

PURPOSE: This study compared two imaging grading techniques to assess the utility of longitudinal image-based analysis in retinopathy of prematurity (ROP) screening: (1) time-limited without image comparison (a proxy for bedside indirect ophthalmoscopy, termed sBIO) and time-unlimited with image comparison (for telemedicine grading, termed TELE) screening. We tested two hypotheses: (1) H1: TELE was superior to sBIO for the detection of change (Tempo)-same, better, or worse and (2) H2: granular data of change (e.g., at the image and feature level) is integrated by graders to achieve the Tempo assessment.

DESIGN: Prospective reliability analysis.

METHODS: Gold standard reference (GS) was a …

Neurodevelopmental Disorder Caused By Deletion Of Chaserr, A Lncrna Gene, Vijay S Ganesh, Kevin Riquin, Nicolas Chatron, Esther Yoon, Kay-Marie Lamar, Miriam C Aziz, Pauline Monin, Melanie C O'Leary, Julia K Goodrich, Kiran V Garimella, Eleina England, Ben Weisburd, François Aguet, Carlos A Bacino, David R Murdock, Hongzheng Dai, Jill A Rosenfeld, Lisa T Emrick, Shamika Ketkar, Yael Sarusi, Damien Sanlaville, Saima Kayani, Brian Broadbent, Alisée Pengam, Bertrand Isidor, Stéphane Bezieau, Benjamin Cogné, Daniel G Macarthur, Igor Ulitsky, Gemma L Carvill, Anne O'Donnell-Luria

Faculty, Staff and Students Publications

No abstract provided.

Demographic Characteristics, Perinatal Smoking Patterns, And Risk For Neonatal Health Complications Among Pregnant Smokers In The United States Who Begin Using Electronic Cigarettes During Pregnancy: A Descriptive Study Using Population-Based Surveillance Data., Hui Nian, Rachel Odland, Samantha Mindlin, Lin Ammar, Hilary Tindle, Angela M Miller, Kelli K Ryckman, Ethan Xie, Tina V Hartert, Brittney M Snyder, Steven M Brunwasser, Pingsheng Wu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy.

AIMS AND METHODS: Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified …

Pediatric Cardiac Xenotransplantation And Expanded Access: Ethical Considerations, Daniel J Hurst, Christopher Bobier, Anthony Merlocco, Luz A Padilla, Daniel Rodger, David Cleveland, John D Cleveland

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Due to the current organ shortage waitlist, alternatives to allotransplantation are necessary. Xenotransplantation is currently being pursued as one such alternative in adults in need of kidney or heart transplantation. Cardiac xenotransplantation of genetically modified pig hearts has been conducted twice in adults under the United States Food and Drug Administration (FDA) expanded access criteria. Because of the shortage of transplantable hearts for children as well as the lack of mechanical circulatory support in this population, pediatric researchers are exploring FDA expanded access in high-risk neonates and infants who lack alternative options for survival. The adult cardiac xenotransplantation experience with …

Genotype And Phenotype Of 21-Hydroxylase Deficiency: A Single Center Experience From Western India, Manjiri Karlekar, Rohit Barnabas, Vijaya Sarathi, Anurag Lila, Sneha Arya, Samiksha Hegishte, Vishwambhar V Bhandare, Saba Samad Memon, Virendra Patil, Tushar Bandgar, Ambarish Kunwar, Nalini Shah

Faculty, Staff and Student Publications

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency.

Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large …

Trends In Gaps Of Care For Patients With Congenital Heart Disease: Implications For Social Determinants Of Health And Child Opportunity Index, Abbas H. Zaidi, Adam Alberts, Devyani Chowdhury, Claude Beaty, Benjamin Brewer, Ming Hui Chen, Sarah D. De Ferranti

Department of Surgery Faculty Papers

BACKGROUND: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood.

METHODS AND RESULTS: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such …

Impact Of Age On Pharmacogenomics And Treatment Outcomes Of B-Cell Acute Lymphoblastic Leukemia, Satoshi Yoshimura, Zhenhua Li, Yoshihiro Gocho, Wenjian Yang, Kristine R Crews, Shawn H R Lee, Kathryn G Roberts, Charles G Mullighan, Mary V Relling, Jiyang Yu, Allen E J Yeoh, Mignon L Loh, Caner Saygin, Mark R Litzow, Sima Jeha, Seth E Karol, Hiroto Inaba, Ching-Hon Pui, Marina Konopleva, Nitin Jain, Wendy Stock, Elisabeth Paietta, Elias Jabbour, Steven M Kornblau, William E Evans, Jun J Yang

Faculty, Staff and Student Publications

Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.

Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations …

Clinical And Functional Studies Of Mtor Variants In Smith-Kingsmore Syndrome Reveal Deficits Of Circadian Rhythm And Sleep-Wake Behavior, Andrew C Liu, Yang Shen, Carolyn R Serbinski, Hongzhi He, Destino Roman, Mehari Endale, Lindsey Aschbacher-Smith, Katherine A King, Jorge L Granadillo, Isabel López, Darcy A Krueger, Thomas J Dye, David F Smith, John B Hogenesch, Carlos E Prada

2020-Current year OA Pubs

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent nine MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell …

Clinical Sequelae Of Gut Microbiome Development And Disruption In Hospitalized Preterm Infants, Robert Thänert, Drew J Schwartz, Eric C Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R S Fishbein, Janice E Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B Warner, Phillip I Tarr, Gautam Dantas

2020-Current year OA Pubs

Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify Enterobacteriaceae, enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. Clostridioides difficile lineages persist between individuals in single centers, and Staphylococcus epidermidis lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut …

Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric …

Maternal Cortisol Concentration Is Associated With Reduced Brain Activation To Infant Cry And More Intrusive Parenting Behavior, Andrew Erhart, Sarah Enos Watamura, Aviva K. Olsavsky, Alexander J. Dufford, Rebekah C. Tribble, Tom Yeh, Pilyoung Kim

Psychology: Faculty Scholarship

Previous research indicates that maternal cortisol function and maternal brain response to infant are each in turn related to variations in parenting behavior. However, little is known about how maternal cortisol and maternal brain function are associated, thus studying these two mechanisms together may improve our understanding of how maternal cortisol assessed during interactions with own infant is associated with brain response to infant cry. First-time mothers (N = 59) of infants aged 3-4 months old were recruited to participate. Mothers' cortisol concentration was measured during a naturalistic interaction with their infant and their behavior was coded for two parenting …

Pre-Procedural Topical Antisepsis In The Neonate: A Systematic Review Evaluating Risk Factors For Skin Injury, Carly Mulinda, Sana Suhail, Bronwyn Sutherland, Christine T Lauren, Raegan D Hunt

Library Staff Publications

BACKGROUND: Pre-procedural antisepsis is a critical component of hospital-acquired infection prevention in the neonatal intensive care unit (NICU). However, broadly utilized topical antiseptic agents pose an elevated risk of disruption to neonatal skin integrity, and evidence-based guidelines are lacking. This systematic review of the literature sought to assess and characterize the predisposing risk factors for and types of neonatal skin injury from topical antiseptic agents.

METHODS: A systematic search of Medline Ovid, Embase, Web of Science, CINAHL, and Cochrane Library was conducted, including academic literature providing data on neonatal skin injuries related to topical antisepsis in the NICU.

RESULTS: A …

Biologic And Clinical Analysis Of Childhood Gamma Delta T-All Identifies Lmo2/Stag2 Rearrangements As Extremely High Risk, Shunsuke Kimura, Chun Shik Park, Lindsey E Montefiori, Ilaria Iacobucci, Petri Pölönen, Qingsong Gao, Elizabeth D Arnold, Andishe Attarbaschi, Anthony Brown, Barbara Buldini, Kenneth J Caldwell, Yunchao Chang, Chelsey Chen, Cheng Cheng, Zhongshan Cheng, John Choi, Valentino Conter, Kristine R Crews, Hester A De Groot-Kruseman, Takao Deguchi, Mariko Eguchi, Hannah E Muhle, Sarah Elitzur, Gabriele Escherich, Burgess B Freeman, Zhaohui Gu, Katie Han, Keizo Horibe, Toshihiko Imamura, Sima Jeha, Motohiro Kato, Kean H Chiew, Tanya Khan, Michal Kicinski, Stefan Köhrer, Steven M Kornblau, Rishi S Kotecha, Chi-Kong Li, Yen-Chun Liu, Franco Locatelli, Selina M Luger, Elisabeth M Paietta, Atsushi Manabe, Hanne V Marquart, Riccardo Masetti, Mellissa Maybury, Pauline Mazilier, Jules P P Meijerink, Sharnise Mitchell, Takako Miyamura, Andrew S Moore, Koichi Oshima, Katarzyna Pawinska-Wasikowska, Rob Pieters, Mollie S Prater, Shondra M Pruett-Miller, Ching-Hon Pui, Chunxu Qu, Michaela Reiterova, Noemi Reyes, Kathryn G Roberts, Jacob M Rowe, Atsushi Sato, Kjeld Schmiegelow, Martin Schrappe, Shuhong Shen, Szymon Skoczeń, Orietta Spinelli, Jan Stary, Michael Svaton, Masatoshi Takagi, Junko Takita, Yanjing Tang, David T Teachey, Paul G Thomas, Daisuke Tomizawa, Jan Trka, Elena Varotto, Tiffaney L Vincent, Jun J Yang, Allen E J Yeoh, Yinmei Zhou, Martin Zimmermann, Hiroto Inaba, Charles G Mullighan

Faculty, Staff and Student Publications

Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in …

Penicillin Susceptibility Among Staphylococcus Aureus Skin And Soft Tissue Infections At A Children’S Hospital, J Chase Mcneil, Lauren M Sommer, Marritta Joseph, Kristina G Hulten, Sheldon L Kaplan

Faculty, Staff and Students Publications

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children’s Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ-negative isolates then underwent penicillin susceptibility …

The Babyseq Project: A Clinical Trial Of Genome Sequencing In A Diverse Cohort Of Infants, Hadley Stevens Smith, Bethany Zettler, Casie A Genetti, Madison R Hickingbotham, Tanner F Coleman, Matthew Lebo, Anna Nagy, Hana Zouk, Lisa Mahanta, Kurt D Christensen, Stacey Pereira, Nidhi D Shah, Nina B Gold, Sheyenne Walmsley, Sarita Edwards, Ramin Homayouni, Graham P Krasan, Hakon Hakonarson, Carol R Horowitz, Bruce D Gelb, Bruce R Korf, Amy L Mcguire, Ingrid A Holm, Robert C Green

Center for Medical Ethics and Health Policy Staff Publications

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States. The trial aims for families who self-identify as Black/African American or Hispanic/Latino to make …

How Do Parents Decide On Genetic Testing In Pediatrics? A Systematic Review, Hadley Stevens Smith, Bethany Zettler, Casie A Genetti, Madison R Hickingbotham, Tanner F Coleman, Matthew Lebo, Anna Nagy, Hana Zouk, Lisa Mahanta, Kurt D Christensen, Stacey Pereira, Nidhi D Shah, Nina B Gold, Sheyenne Walmsley, Sarita Edwards, Ramin Homayouni, Graham P Krasan, Hakon Hakonarson, Carol R Horowitz, Bruce D Gelb, Bruce R Korf, Amy L Mcguire, Ingrid A Holm, Robert C Green

Center for Medical Ethics and Health Policy Staff Publications

Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015-2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States. The trial aims for families who self-identify as Black/African American or Hispanic/Latino to make …

Microfluidic Affinity Selection Of B-Lineage Cells From Peripheral Blood For Minimal Residual Disease Monitoring In Pediatric B-Type Acute Lymphoblastic Leukemia Patients., Malgorzata A. Witek, Nicholas E. Larkey, Alena Bartakova, Mateusz L. Hupert, Shalee Mog, Jami K. Cronin, Judy Vun, Keith August, Steven A. Soper

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate …

Pulse Oximetry Accuracy In Children With Dark Skin Tones: Relevance To Acute Lower Respiratory Infection Care In Low- And Middle-Income Countries, Shubhada Hooli, Tim Colbourn, Manish I Shah, Kristy Murray, Anna Mandalakas, Eric D Mccollum

Faculty, Staff and Students Publications

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) < 90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.