Medicine and Health Sciences Commons^™

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

Sex Difference Leads To Differential Gene Expression Patterns And Therapeutic Efficacy In Mucopolysaccharidosis Iva Murine Model Receiving Aav8 Gene Therapy, Matthew Matthew Piechnik, Paige C. Amendum, Kazuki Sawamoto, Molly Stapleton, Shaukat Khan, Nidhi Fnu, Victor Álvarez, Angelica Maria Herreño Pachon, Olivier Danos, Joseph T. Bruder, Subha Karumuthil-Melethil, Shunji Tomatsu

Student Papers, Posters & Projects

Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting …

Safety And Efficacy Of Voxelotor In Pediatric Patients With Sickle Cell Disease Aged 4 To 11 Years., Jeremie H. Estepp, Ram Kalpatthi, Gerald Woods, Sara Trompeter, Robert I. Liem, Kacie Sims, Adlette Inati, Baba P D Inusa, Andrew Campbell, Connie Piccone, Miguel R. Abboud, Kim Smith-Whitley, Sandra Dixon, Margaret Tonda, Carla Washington, Noelle M. Griffin, Clark Brown

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality.

PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization …

Validation Of Remote Height And Weight Assessment In A Rural Randomized Clinical Trial., Bethany Forseth Hanson, Ann M. Davis, Dana Bakula, Megan Murray, Kelsey Dean, Rebecca E. Swinburne Romine, Kandace Fleming

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The purpose of this study is to describe and assess a remote height and weight protocol that was developed for an ongoing trial conducted during the SARS COV-2 pandemic.

METHODS: Thirty-eight rural families (children 8.3 ± 0.7 years; 68% female; and caregivers 38.2 ± 6.1 years) were provided detailed instructions on how to measure height and weight. Families obtained measures via remote data collection (caregiver weight, child height and weight) and also by trained staff. Differences between data collection methods were examined.

RESULTS: Per absolute mean difference analyses, slightly larger differences were found for child weight (0.21 ± 0.21 …

Analysis Of Neonatal Neurobehavior And Developmental Outcomes Among Preterm Infants., Elisabeth C. Mcgowan, Julie A. Hofheimer, T Michael O'Shea, Howard Kilbride, Brian S. Carter, Jennifer Check, Jennifer Helderman, Charles R. Neal, Steve Pastyrnak, Lynne M. Smith, Marie Camerota, Lynne M. Dansereau, Sheri A. Della Grotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed.

Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes.

Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to …

Sex-Specific Alterations In Hepatic Cholesterol Metabolism In Low Birth Weight Adult Guinea Pigs., Ousseynou Sarr, Katherine E Mathers, Christina Vanderboor, Kristina Wiggers, Aditya Devgan, Daniel B Hardy, Lin Zhao, Timothy Regnault

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction and low birth weight (LBW) have been widely reported as an independent risk factor for adult hypercholesterolaemia and increased hepatic cholesterol in a sex-specific manner. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.

METHODS: Hepatic cholesterol, transcriptome, cholesterol homoeostasis regulatory proteins, and antioxidant markers were studied in UPI-induced LBW and normal birth weight (NBW) male and female guinea pigs at 150 days.

RESULTS: Hepatic free and …

Association Of Abnormal Findings On Neonatal Cranial Ultrasound With Neurobehavior At Neonatal Intensive Care Unit Discharge In Infants Born Before 30 Weeks' Gestation., Jennifer Helderman, T Michael O'Shea, Lynne Dansereau, Jennifer Check, Julie A. Hofheimer, Lynne M. Smith, Elisabeth Mcgowan, Charles R. Neal, Brian S. Carter, Steven L. Pastyrnak, Bradford Betz, Joseph Junewick, Heather L. Borders, Sheri A. Dellagrotta, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Cranial ultrasound (CUS) findings are routinely used to identify preterm infants at risk for impaired neurodevelopment, and neurobehavioral examinations provide information about early brain function. The associations of abnormal findings on early and late CUS with neurobehavior at neonatal intensive care unit (NICU) discharge have not been reported.

Objective: To examine the associations between early and late CUS findings and infant neurobehavior at NICU discharge.

Design, Setting, and Participants: This prospective cohort study included infants enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study between April 2014 and June 2016. Infants born before 30 weeks' gestational …

A Taxonomy Of Childhood Pedal Cyclist Injuries From Latent Class Analysis: Associations With Factors Pertinent To Prevention, Joseph Piatt

Department of Neurosurgery Faculty Papers

Background: Studies of pedal cyclist injuries have largely focused on individual injury categories, but every region of the cyclist's body is exposed to potential trauma. Real-world injury patterns can be complex, and isolated injuries to one body part are uncommon among casualties requiring hospitalization. Latent class analysis (LCA) may identify important patterns in heterogeneous samples of qualitative data.

Methods: Data were taken from the Trauma Quality Improvement Program of the American College of Surgeons for 2017. Inclusion criteria were age 18 years or less and an external cause of injury code for pedal cyclist. Injuries were characterized by Abbreviated Injury …

Clinical Utility Of Anti-Mullerian Hormone In Pediatrics, Roopa Kanakatti Shankar, Tazim Dowlut-Mcelroy, Andrew Dauber, Veronica Gomez-Lobo

Pediatrics Faculty Publications

CONTEXT: Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.

DESIGN AND RESULTS: A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. …