Medical Specialties Commons^™

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 …

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

Faculty, Staff and Student Publications

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …

Single-Cell Integration Reveals Metaplasia In Inflammatory Gut Diseases, Amanda J Oliver, Ni Huang, Raquel Bartolome-Casado, Ruoyan Li, Simon Koplev, Hogne R Nilsen, Madelyn Moy, Batuhan Cakir, Krzysztof Polanski, Victoria Gudiño, Elisa Melón-Ardanaz, Dinithi Sumanaweera, Daniel Dimitrov, Lisa Marie Milchsack, Michael E B Fitzpatrick, Nicholas M Provine, Jacqueline M Boccacino, Emma Dann, Alexander V Predeus, Ken To, Martin Prete, Jonathan A Chapman, Andrea C Masi, Emily Stephenson, Justin Engelbert, Sebastian Lobentanzer, Shani Perera, Laura Richardson, Rakeshlal Kapuge, Anna Wilbrey-Clark, Claudia I Semprich, Sophie Ellams, Catherine Tudor, Philomeena Joseph, Alba Garrido-Trigo, Ana M Corraliza, Thomas R W Oliver, C Elizabeth Hook, Kylie R James, Krishnaa T Mahbubani, Kourosh Saeb-Parsy, Matthias Zilbauer, Julio Saez-Rodriguez, Marte Lie Høivik, Espen S Bækkevold, Christopher J Stewart, Janet E Berrington, Kerstin B Meyer, Paul Klenerman, Azucena Salas, Muzlifah Haniffa, Frode L Jahnsen, Rasa Elmentaite, Sarah A Teichmann

Faculty, Staff and Student Publications

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning …

Burden Re-Analysis Of Neurodevelopmental Disorder Cohorts For Prioritization Of Candidate Genes, Noor Smal, Fatma Majdoub, Katrien Janssens, Edwin Reyniers, Marije E C Meuwissen, Berten Ceulemans, Hope Northrup, Jeremy B Hill, Lingying Liu, Edoardo Errichiello, Simone Gana, Alanna Strong, Luis Rohena, Rachel Franciskovich, Chaya N Murali, An Huybrechs, Telma Sulem, Run Fridriksdottir, Patrick Sulem, Kari Stefansson, Yan Bai, Jill A Rosenfeld, Seema R Lalani, Haley Streff, Undiagnosed Diseases Network, R Frank Kooy, Sarah Weckhuysen

Faculty, Staff and Students Publications

This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden …

Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Yue Huang, Kristy L Jay, Alden Yen-Wen Huang, Jijun Wan, Sharayu V Jangam, Odelia Chorin, Annick Rothschild, Ortal Barel, Milena Mariani, Maria Iascone, Han Xue, Undiagnosed Diseases Network, Jing Huang, Cyril Mignot, Boris Keren, Virginie Saillour, Annelise Y Mah-Som, Stephanie Sacharow, Farrah Rajabi, Carrie Costin, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Jill A Rosenfeld, Christina G S Palmer, Stanley F Nelson, Michael F Wangler, Julian A Martinez-Agosto

Faculty, Staff and Students Publications

PURPOSE: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

METHODS: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.

RESULTS: Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the …

Biallelic Loss-Of-Function Variants In Ubap1l And Nonsyndromic Retinal Dystrophies, Ehsan Ullah, Siying Lin, Jiaxiong Lu, Chelsea Bender, Andrew R Webster, Samantha Malka, Savita Madhusudhan, Emma Rees, Denise Williams, Aime R Agather, Catherine A Cukras, Robert B Hufnagel, Rui Chen, Laryssa A Huryn, Gavin Arno, Bin Guan

Faculty, Staff and Students Publications

Importance: Inherited retinal dystrophies (IRDs) present a challenge in clinical diagnostics due to their pronounced genetic heterogeneity. Despite advances in next-generation sequencing (NGS) technologies, a substantial portion of the genetic basis underlying IRDs remains elusive. Addressing this gap seems important for gaining insights into the genetic landscape of IRDs, which may help improve diagnosis and prognosis and develop targeted therapies in the future.

Objective: To provide a clinical and molecular characterization of 6 patients with IRDs with biallelic disease-causing variants in a novel candidate IRD disease gene.

Design, setting, and participants: This multicenter case series study included 6 patients with …

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; …

Iron Deficiency And Internalizing Symptoms Among Adolescents In The National Health And Nutrition Examination Survey, Dimitri Fiani, Solangia Engler, Yang Ni, Sherecce Fields, Chadi Calarge

Faculty, Staff and Students Publications

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans.

Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association …

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.

Optical Genome Mapping For Detection Of Bcr::Abl1-Another Tool In Our Toolbox, Zhenya Tang, Wei Wang, Gokce A Toruner, Shimin Hu, Hong Fang, Jie Xu, M James You, L Jeffrey Medeiros, Joseph D Khoury, Guilin Tang

Faculty, Staff and Student Publications

Background:BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up.

Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1.

Results:BCR:ABL1 was detected by FISH and RT-PCR …

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 …

Acute On Chronic Rheumatic Valvulitis, Natalie K Craik, Joseph Burns, Nirica Borges, Tam T Doan, Amy E Sanyahumbi, Edward J Hickey, Debra L Kearney, Ryan H Rochat, Eyal Muscal, Thomas Glenn

Faculty, Staff and Students Publications

An 11-year-old boy presented in distress with tachypnea, holosystolic murmur, and a gallop. Echocardiography revealed mitral valve thickening and severe regurgitation. He required valve replacement with pathology consistent with acute on chronic valvulitis. This case underscores the importance of considering rheumatic heart disease, despite no preceding suspicious history.

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 …

Exposure To Per- And Polyfluoroalkyl Substances And Alterations In Plasma Microrna Profiles In Children, Yijie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Haotian Wu, Shelley H Liu, Hongxu Wang, Emily Beglarian, Scott M Bartell, Sandrah Proctor Eckel, Douglas Walker, Damaskini Valvi, Michele Andrea La Merrill, Thomas H Inge, Todd Jenkins, Justin R Ryder, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Marina Vafeiadi, Aikaterini Margetaki, Theano Roumeliotaki, Max Aung, Rob Mcconnell, Andrea Baccarelli, David Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans.

OBJECTIVE: To investigate associations between PFAS concentrations and miRNA levels in children.

METHODS: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and …

Clean Intermittent Catheterisation Determinants And Caregiver Adherence In Paediatric Patients With Spinal Dysraphism And Spinal Cord Injury In A Paediatric Spinal Differences Clinic: A Mixed Methods Study Protocol., Azadeh Wickham, Cynthia L. Russell, John Gatti

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Clean intermittent catheterisation (CIC) is the standard of care for treating neurogenic lower urinary tract dysfunction (NLUTD), the most common bladder dysfunction in children diagnosed with spinal dysraphism (SD) and spinal cord injury (SCI). Failure to follow the prescribed CIC regimen results in urinary tract infections, incontinence and renal insufficiency. Adherence to CIC is suboptimal, with reported non-adherence rates of 18%-66%. Despite the efficacy of CIC, the research on CIC adherence is not well defined in the literature and even less for caregivers of children on CIC protocols.

METHODS: This proposed study aims to identify caregiver CIC adherence and …

Larp1 Haploinsufficiency Is Associated With An Autosomal Dominant Neurodevelopmental Disorder, James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R Dupont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and …

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 …

Implementation Study Of The Carra Uveitis Consensus Treatment Plans: Feasibility For Clinical Practice And Applicability For Research., Margaret H. Chang, Fatima Barbar-Smiley, Shoghik Akoghlanian, Joanne Drew, Sheila T. Angeles-Han, Megan Quinlan-Waters, John F. Bohnsack, Ashley M. Cooper, Barbara Edelheit, Jennifer Twachtman-Bassett, Melissa A. Lerman, Kabita Nanda, C Egla Rabinovich, Mindy S. Lo, Carra Uveitis Workgroup And The Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic anterior uveitis (CAU) carries a significant risk for eye complications and vision loss. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) introduced consensus treatment plans (CTPs) to standardize treatment for CAU and facilitate future comparative effectiveness studies. Two CTPs were developed to address: 1) initiation of methotrexate (MTX) in patients with CAU naïve to steroid-sparing therapy, and 2) initiation of a TNF inhibitor (TNFi) in patients with severe uveitis or uveitis refractory to MTX. We evaluated implementation of the uveitis CTPs using existing CARRA Registry infrastructure and assessed feasibility of the CTPs for comparative effectiveness research.

METHODS: This …

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 Cochlear Dose And The Age At Radiotherapy Predict Severe Hearing Loss After Passive Scattering Proton Therapy And Cisplatin In Children With Medulloblastoma, Mohammad H Abu-Arja, Austin L Brown, Jack M Su, M Fatih Okcu, Holly B Lindsay, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Murali M Chintagumpala, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin.

Methods: We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI).

Results: Seventy-nine patients …

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.

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 …

Pancreatic Enzyme Use Reduces Pancreatitis Frequency In Children With Acute Recurrent Or Chronic Pancreatitis: A Report From Insppire, Alvin Jay Freeman, Kenneth Ng, Fuchenchu Wang, Maisam A Abu-El-Haija, Ankur Chugh, Gretchen A Cress, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Praveen Goday, Tanja Y Gonska, Amit S Grover, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Robert A Noel, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Dana K Andersen, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Introduction: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.

Methods: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after …

Isolated Psychiatric Symptoms In Children With Anti-N-Methyl-D Aspartate Receptor Encephalitis, Grace Gombolay, J Nicholas Brenton, Jennifer H Yang, Coral M Stredny, Ryan Kammeyer, Kristen S Fisher, Alexander J Sandweiss, Timothy A Erickson, Varun Kannan, Catherine Otten, Claude Steriade, Ngochanh Vu, Jonathan D Santoro, Karla Robles-Lopez, Robert Goodrich, Scott Otallah, Janetta Arellano, Andrew Christiana, Morgan Morris, Mark P Gorman, Alexandra B Kornbluh, Ilana Kahn, Leigh Sepeta, Yike Jiang, Eyal Muscal, Kristy O Murray, Manikum Moodley, Duriel Hardy

Faculty, Staff and Students Publications

Background: Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE.

Methods: This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data …

Anger Outbursts In Youth With Asd And Anxiety: Phenomenology And Relationship With Family Accommodation, Allie N Townsend, Andrew G Guzick, Alyssa G Hertz, Connor M Kerns, Wayne K Goodman, Leandra N Berry, Philip C Kendall, Jeffrey J Wood, Eric A Storch

Faculty, Staff and Students Publications

Anger outbursts (AO) are associated with severe symptoms, impairment and poorer treatment outcomes for anxious children, though limited research has examined AO in youth with co-occurring autism and anxiety disorders. This study examined AO in children with autism and anxiety by evaluating clinical characteristics, family accommodation, and changes in AO following anxiety-focused treatment. The sample comprised 167 youth with autism and anxiety enrolled in a multi-site randomized clinical trial comparing standard care CBT for anxiety, CBT adapted for youth with autism, and usual care. Most participants (60%) had AO, which contributed to impairment above and beyond anxiety and autism. AO …

The Relationship Between Adverse Childhood Experiences, Symptom Severity, Negative Thinking, Comorbidity, And Treatment Response In Youth With Obsessive-Compulsive Disorder, Mariana Vazquez, Amanda Palo, Mckenzie Schuyler, Brent J Small, Joseph F Mcguire, Sabine Wilhelm, Wayne K Goodman, Daniel Geller, Eric A Storch

Faculty, Staff and Students Publications

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE …

Challenges In Pediatric Home-Based Hospice And Palliative Care: A Case Series, Jill Ann Jarrell, Daniel H Grossoehme, Sarah Friebert, Toluwalase A Ajayi, Rachel Thienprayoon, Lisa Humphrey

Faculty, Staff and Students Publications

Pediatric home-based hospice and palliative care is a growing and important sub-field within the larger pediatric palliative care landscape. Despite research demonstrating the clinical and systemic efficacy of pediatric home-based hospice and palliative care, there remain barriers to its optimal development, implementation, and dissemination as well as best clinical practice knowledge gaps. This case series presents specific examples of ubiquitous challenges in pediatric home-based hospice and palliative care in hopes of guiding future research, education, advocacy, and program development efforts.

Influenza C Virus In Us Children With Acute Respiratory Infection 2016–2019, Bethany K Sederdahl, Geoffrey A Weinberg, Angela P Campbell, Rangaraj Selvarangan, Jennifer E Schuster, Joana Y Lively, Samantha M Olson, Julie A Boom, Pedro A Piedra, Natasha B Halasa, Laura Stewart, Peter G Szilagyi, G K Balasubramani, Theresa Sax, Judith M Martin, Robert W Hickey, Marian G Michaels, John V Williams, New Vaccine Surveillance Network

Faculty, Staff and Students Publications

Influenza C virus (ICV) is an orthomyxovirus related to influenza A and B, yet due to few commercial assays, epidemiologic studies may underestimate incidence of ICV infection and disease. We describe the epidemiology and characteristics of ICV within the New Vaccine Surveillance Network (NVSN), a Centers for Disease Control and Prevention (CDC)-led network that conducts population-based surveillance for pediatric acute respiratory illness (ARI). Nasal or/combined throat swabs were collected from emergency department (ED) or inpatient ARI cases, or healthy controls, between 12/05/2016-10/31/2019 and tested by molecular assays for ICV and other respiratory viruses. Parent surveys and chart review were used …

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022, Alpha Oumar Diallo, Mary E Wikswo, Iddrisu Sulemana, Leila C Sahni, Julie A Boom, Sasirekha Ramani, Rangaraj Selvarangan, Mary E Moffatt, Christopher J Harrison, Natasha Halasa, James Chappell, Laura Stewart, Mary Allen Staat, Elizabeth Schlaudecker, Christina Quigley, Eileen J Klein, Janet A Englund, Danielle M Zerr, Geoffrey A Weinberg, Peter G Szilagyi, Christina Albertin, Samantha H Johnston, John V Williams, Marian G Michaels, Robert W Hickey, Aaron T Curns, Michelle Honeywood, Slavica Mijatovic-Rustempasic, Mathew D Esona, Michael D Bowen, Umesh D Parashar, Rashi Gautam, Sara A Mirza, Jacqueline E Tate

Faculty, Staff and Students Publications

Background: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022).

Methods: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or …