Medicine and Health Sciences Commons^™

A Scoping Review Of Patient Safety Checklists In Pediatrics, Kawtar Zouaidi, Tate W Miner, Muhammad F Walji, Kristin N Ray, Elsbeth Kalenderian, Donald B Rindal, Katie J Suda

Faculty, Staff and Student Publications

Objective: To examine the utilization and effectiveness of safety checklists in pediatric clinical care.

Methods: A comprehensive literature search was conducted using Medline to identify studies related to the development and/or implementation of patient safety checklists in pediatrics. All study designs were included for citations published through September 2023.

Results: Following abstract and full-text screening, 74 studies remained for data extraction and analysis. Pediatric surgery emerged as the main setting for checklists use (n = 35), followed by Intensive Care Units (n = 21), and Emergency Departments (n = 9). Of the 74 reviewed papers, 37 (50%) designed and developed …

Phenotypic Variation In Disease Severity Among Hospitalized Pediatric Patients With Covid-19: Assessing The Impact Of Covid-19 In The Epico Study, María Camila Sossa-Alarcón, Mónica Paola Gutiérrez, Natalia Becerra, Luz Yessenia Ortegon, María Camila David, Melisa Naranjo Vanegas, Gabriela Friedrich, Pablo Vásquez-Hoyos, María Lucía Mesa-Rubio, Luis Miguel Navarro-Ramirez, Sergio Moreno-Lopez, Olga Lucía Baquero, Luz Marina Mejía, Juan Gabriel Piñeros, Sonia Restrepo-Gualteros, Carlos Álvarez-Moreno, Alejandro Díaz-Díaz, Iván Gutierrez-Tobar, Andrés Camilo Mesa, William Ricardo Bachiller Tuta, Clara Esperanza Galvis Diaz, Martha Africano, José Manuel Nieto, Paola Marsela Pérez Camacho, Claudia Beltrán-Arroyave, Rosalba Vivas Trochez, Irati Gastesi, Cinta Moraleda, Alfredo Tagarro García, Blanca Herrero, Lourdes Calleja, Carlos Grasa, Paula Rodriguez, Susana Melendo, Antoni Soriano-Arandes, Irene Gómez Pastrana, Sonsoles García García, Victoria Fumado, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Objective: To characterize the clinical phenotypes of SARS-CoV-2 infection in hospitalized children as part of the EPICO multicenter cohort study.

Methods: We included hospitalized children with confirmed SARS-CoV-2 infection from Colombian and Spanish institutions to assess disease evolution and outcomes. Cluster analysis was performed to identify clinical phenotypes.

Results: A total of 2318 patients were included (55% male, 36% infants). Five phenotype clusters emerged: Cluster 1 (26.5%): infants without comorbidities, low PICU admissions and mortality; Cluster 2 (18.5%): respiratory comorbidities, high microorganism co-detection and mortality; Cluster 3 (11.5%): fever, gastrointestinal symptoms, high PICU admissions; Cluster 4 (32%): mild unspecific symptoms, …

A Comparison Of Floating Catchment Area Parameters With Applications To A Dataset Of Clinics Enrolled In A Statewide Child And Adolescent Psychiatric Consultation Program, Jocelyn Hunyadi, Lara S Savas, Kehe Zhang, Jeanette E Deason, Ryan Ramphul, Melissa F Peskin, Erica L Frost, Cici Bauer

Faculty, Staff and Student Publications

INTRODUCTION: Healthcare resources are often crucial but limited, requiring careful consideration and informed allocation based on population needs and potential healthcare access. In resource allocation settings, availability and accessibility of resources should be examined simultaneously. The two-step floating catchment area (2SFCA) method has been previously used to evaluate spatial accessibility to healthcare resources and services, and to address health-related disparities. The 2SFCA methods have regained significant popularity during the COVID-19 pandemic, as their application proved crucial in addressing priority public health data analysis, modeling, and accessibility challenges. However, comprehensive comparisons of the 2SFCA method input parameters in the context of …

The Management Of Dietary Fiber Intake In Children With Chronic Kidney Disease - Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., An Desloovere, Nonnie Polderman, José Renken-Terhaerdt, Vanessa Shaw, Caroline Anderson, Larry A. Greenbaum, Christina L. Nelms, Leila Qizalbash, Stella Stabouli, Jetta Tuokkola, Bradley A. Warady, Johan Vande Walle, Fabio Paglialonga, Rukshana Shroff, Evelien Snauwaert

Manuscripts, Articles, Book Chapters and Other Papers

The benefits of dietary fiber are widely accepted. Nevertheless, a substantial proportion of children fail to meet the recommended intake of dietary fiber. Achieving adequate fiber intake is especially challenging in children with chronic kidney disease (CKD). An international team of pediatric renal dietitians and pediatric nephrologists from the Pediatric Renal Nutrition Taskforce (PRNT) has developed clinical practice recommendations (CPRs) for the dietary intake of fiber in children and adolescents with CKD. In this CPR paper, we propose a definition of fiber, provide advice on the requirements and assessment of fiber intake, and offer practical guidance on optimizing dietary fiber …

Grade Notes 4: How To Use Grade When There Is "No" Evidence? A Case Study Of Using Unpublished Registry Data., Ibrahim K. El Mikati, Brandy Begin, Dagmara Borzych-Duzalka, Alicia M. Neu, Troy Richardson, Rebecca G. Same, Franz Schaefer, Bradley A. Warady, Reem A. Mustafa

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Trustworthy guidelines rely on systematic reviews of the best available published evidence. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) Working Group has provided guidance about developing evidence-based recommendations when published direct evidence is lacking. In this article, we provide a case example as an alternate solution to generate primary data using registries prior to collecting expert evidence.

STUDY DESIGN AND SETTING: When direct published literature was absent, a team of clinical and statistical expertise can utilize registries, when available, for primary data generation in a way that allows for answering clinically important questions.

RESULTS: Out of 54 …

Congenital Posterior Urethroperineal Fistula Presenting As A Cystic Mass, Muhammad Siddiqui, Sang Woo Pak, Preeya Mistry, Sarah Starnes, Stacy White, Anthony Zarka, Lori Gurien

South Atlantic Division GME Research Day 2025

No abstract provided.

Management Of Upper Extremity Hemihyperplasia In Beckwidth-Wiedman Syndrome: A Pediatric Case Over The Course Of 9 Years, Savannah Yeh, Nancy Jimenez, Vidhur Sohini, Jonathan R. Sorelle

South Atlantic Division GME Research Day 2025

No abstract provided.

Examining Low-Income Caregivers' Knowledge And Comprehension Of The Dental Caries Process, Melissa Sullivan, Denise C. Mckinney, Deanne Shuman, Qi Zhang

Dental Hygiene Faculty Publications

Purpose Dental caries among young children remains a public health concern in the United States (US). Children of caregivers with low oral health literacy (OHL) tend to have greater unmet dental needs and poorer oral health status. The purpose of this study was to examine the understanding of pediatric dental terms associated with the dental caries process among low-income caregivers.

Methods This study included 14 caregivers with children enrolled in a Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in the Southeastern US. Through structured phone interviews, the validated Oral Health Literacy Inventory for Parents (OH-LIP) was used …

Invasive Fungal Disease In Solid Organ And Hematopoietic Cell Transplant Recipients, United States, Jeremy A W Gold, Kaitlin Benedict, Elizabeth Sajewski, Tom Chiller, Meghan Lyman, Mitsuru Toda, Jessica S Little, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

Background: Updated benchmark data on invasive fungal disease (IFD) in solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) recipients are necessary to increase clinical recognition and inform treatment and prevention strategies. We estimated IFD incidence and potential risk factors in transplant recipients in a large US commercial health insurance database.

Methods: We observed patients who received SOT or HCT during 2018-2022 until IFD development, disenrollment, or database end date (July 31, 2023). We calculated incidence (per 1000 person-years) and time to IFD development, comparing demographic features and underlying conditions for IFD versus non-IFD patients.

Results: Overall, 9143 patients received …

Nutritional Management Of The Child With Chronic Kidney Disease And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Lyndsay Harshman, Christina L. Nelms, Pearl Pugh, Nonnie Polderman, José Renken-Terhaerdt, Evelien Snauwaert, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Fabio Paglialonga, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

While it is widely accepted that the nutritional management of the infant with chronic kidney disease (CKD) is paramount to achieve normal growth and development, nutritional management is also of importance beyond 1 year of age, particularly in toddlers, to support the delayed infantile stage of growth that may extend to 2-3 years of age. Puberty is also a vulnerable period when nutritional needs are higher to support the expected growth spurt. Inadequate nutritional intake throughout childhood can result in failure to achieve full adult height potential, and there is an increased risk for abnormal neurodevelopment. Conversely, the rising prevalence …

International Multicenter Retrospective Study From The Ultra-Rare Sarcoma Working Group On Low-Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, And Hybrid Forms: Outcome Of Primary Localized Disease, Claudia Giani, Abdulazeez Salawu, Silva Ljevar, Ryan A Denu, Andrea Napolitano, Emanuela Palmerini, Elizabeth A Connolly, Koichi Ogura, Daniel D Wong, Roberto Scanferla, Evan Rosenbaum, Jyoti Bajpai, Zola Chia-Chen Li, Susie Bae, Lorenzo D'Ambrosio, Steve Bialick, Andrew J Wagner, Alexander T J Lee, Hanna Koseła-Paterczyk, Giacomo G Baldi, Antonella Brunello, Yeh Chen Lee, Herbert H Loong, Sosipatros Boikos, Fernando Campos, Carlo M Cicala, Robert G Maki, Nadia Hindi, Costanza Figura, Shahd S Almohsen, Sheyaskumar Patel, Robin L Jones, Toni Ibrahim, Rooshdiya Karim, Akira Kawai, Richard Carey-Smith, Richard Boyle, Silvia M Taverna, Alexander J Lazar, Elizabeth G Demicco, Judith V M G Bovee, Angelo P Dei Tos, Christopher Fletcher, Daniel Baumhoer, Marta Sbaraglia, Inga-Marie Schaefer, Rosalba Miceli, Alessandro Gronchi, Silvia Stacchiotti

Faculty, Staff and Student Publications

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. …

Effect Of Palatoplasty Technique On Otologic Outcomes In Children With Cleft Palate, Shaina W Gong, Paul Hung, Chioma G Obinero, Jose Barrera, Zi Yang Jiang, Matthew R Greives, Zhen Huang

Faculty, Staff and Student Publications

Background: In patients with cleft palate (CP), the impact of primary palatoplasty technique on otologic outcomes remains a major point of contention. While some studies report improved outcomes after certain techniques of palatal repair, there is a lack of consensus on the most effective procedure.

Objective: We sought to characterize the effects of primary palatoplasty technique on otologic outcomes in children with CP.

Methods: A single institution retrospective review of patients with CP who underwent primary palatoplasty (straight-line repair or Furlow Z-plasty) was performed. Primary outcomes of interest included time to placement of T-tubes, number of tympanostomy tube placements, tympanic …

Accumulated Seizure Burden Predicts Neurodevelopmental Outcome At 36 Months Of Age In Patients With Tuberous Sclerosis Complex, S Katie Z Ihnen, Samuel Alperin, Jamie K Capal, Alexander L Cohen, Jurriaan M Peters, E Martina Bebin, Hope A Northrup, Mustafa Sahin, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear.

Methods: Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of …

Efficacy And Safety Of Once-Daily Roflumilast Cream 005% In Pediatric Patients Aged 2-5 Years With Mild-To-Moderate Atopic Dermatitis (Integument-Ped): A Phase 3 Randomized Controlled Trial, Lawrence F Eichenfield, Rocco Serrao, Vimal H Prajapati, John C Browning, Lisa Swanson, Tracy Funk, Mercedes E Gonzalez, Adelaide A Hebert, Mark Lee, Mark Boguniewicz, Eric L Simpson, Melissa S Seal, David Krupa, Diane Hanna, Scott Snyder, Patrick Burnett, David H Chu, Erin Almaraz, Robert C Higham, David R Berk

Faculty, Staff and Student Publications

Background/objectives: Efficacy and safety of roflumilast cream 0.15% were demonstrated in patients aged ≥ 6 years with atopic dermatitis (AD) in two Phase 3 trials. This Phase 3 parallel-group, double-blind trial (INTEGUMENT-PED; NCT04845620) compared the efficacy and safety of roflumilast cream 0.05% and a vehicle in patients aged 2-5 years with AD.

Methods: Patients aged 2-5 years with mild-to-moderate AD were treated with once-daily roflumilast cream 0.05% or vehicle for 4 weeks. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (0 [Clear] or 1 [Almost Clear] plus ≥ 2-grade improvement from baseline) at Week …

Comprehensive Genomic Analysis Reveals Molecular Heterogeneity In Pediatric Alk-Positive Anaplastic Large Cell Lymphoma, Timothy I Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S Lim, Vasiliki Leventaki

Faculty, Staff and Student Publications

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription …

National Landscape Of Underrepresented In Medicine Visiting Medical Student Programs In Pediatrics, Tyler K Smith, Rebecca Blankenburg, Ann E Burke, Emma A Omoruyi, Wendla Sensing, Tiffany Ruan, David D Williams, Onyi Oligbo, Lahia Yemane

Faculty, Staff and Student Publications

Objective: Underrepresented in medicine visiting medical student programs (UIM-VMSPs) have gained popularity across specialties as an intervention to diversify residency programs; however, no study has explored the national landscape of these programs in pediatrics. This study aimed to characterize program components, residency rank and match outcomes, benefits, challenges, and lessons learned about UIM-VMSPs in pediatrics nationally.

Methods: From September to December 2023, the authors conducted a national, cross-sectional, mixed methods study surveying program leaders of UIM-VMSPs identified on the Association of Pediatric Program Directors website. The authors used descriptive statistics to analyze the data and conventional content analysis for free-text …

Improved Survival And Decreased Cancer Deaths In Young Adults With Cancer After Passage Of The Affordable Care Act Dependent Coverage Expansion, Michael Roth, Clark R Andersen, Amy Berkman, Stuart Siegel, Branko Cuglievan, J Andrew Livingston, Michelle Hildebrandt, Jaime Estrada, Archie Bleyer

Faculty, Staff and Student Publications

Background: The Patient Protection and Affordable Care Act (ACA) allowed Americans aged 19-25 years to remain on their parents' health insurance plans until age 26 years (the Dependent Care Expansion [DCE]). Have those with cancer diagnoses benefited?

Methods: The ACE DCE 7-year age range of 19-25 years was compared for changes in cancer survival and mortality before and after enactment of the ACA with groups that were younger and older (in 7-year age spans: ages 12-18 and 26-32 years, respectively). Cancer death data for the entire United States were obtained from the Centers for Disease Control and Prevention, and relative …

Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos

Faculty, Staff and Student Publications

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Jennifer A Belsky, Ashley Chavana, Ankona Banerjee, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …

Med12 Loss-Of-Function Variants As A Cause Of Congenital Diaphragmatic Hernia In Females With Hardikar Syndrome And Nonspecific Intellectual Disability, Eric C Kao, Elizabeth A Mizerik, Carlos A Bacino, Hongzheng Dai, Liesbeth Vossaert, Daryl A Scott

Faculty, Staff and Students Publications

Mediator complex subunit 12 (MED12) is required for the assembly of the kinase module of Mediator, a regulatory complex that controls the formation of the RNA polymerase II-mediated preinitiation complex. MED12-related disorders display unique gender-specific genotype-phenotype associations and include X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants, and X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de novo nonsense/frameshift and nonsense/missense variants, respectively. MED12 was previously identified as a low-penetrance candidate gene for non-isolated congenital diaphragmatic hernia (CDH+). At the time, however, there was …

Evaluation Of Methotrexate Pharmacogenomic Variation To Predict Acute Neurotoxicity In Children With Acute Lymphoblastic Leukemia, Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

BACKGROUND: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

METHODS: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance …

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Emily R Waskow, Lisa T Emrick, Jill A Rosenfeld, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott

Faculty, Staff and Students Publications

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the …

Impact Of Elevated Serum Triglycerides On Children With Acute Recurrent Or Chronic Pancreatitis From Insppire-2, Zachary M Sellers, Matthew J Giefer, Fuchenchu Wang, Gretchen A Cress, Maisam A Abu-El-Haija, Ankur Chugh, Reuven Z Cohen, Elissa M Downs, Douglas S Fishman, A Jay Freeman, Cheryl E Gariepy, Tanja Y Gonska, Amit S Grover, Doug Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Kenneth Ng, Robert A Noel, Chee Y Ooi, Emily R Perito, Madhura Y Phadke, Wenly Ruan, Sarah Jane Schwarzenberg, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (< 150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.

Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Critiques Of The Cass Review: Fact-Checking The Peer-Reviewed And Grey Literature, Kathleen Mcdeavitt, J Cohn, Stephen B Levine

Faculty, Staff and Students Publications

The Cass Review's final report, published in April 2024, made recommendations to the UK's National Health Service regarding structuring of services for minors with gender-related distress. It recommended cautious use of hormonal interventions in this population and use of research protocols. Some clinician-researchers disagree with the Cass Review's recommendations and have written critiques. A critique of the Cass Review posted on Yale Law School's website in July 2024 has received extensive media coverage. Its references identified three other critiques. In these papers, there were multiple claims that were incorrect or that lacked essential clarification/contextualization. These claims involved (1) the Cass …

Detection Of Viral Rna And Dna And Immune Response Following Administration Of Live Attenuated Measles And Varicella Vaccines In Children With Chronic Liver Disease, Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman

Faculty, Staff and Students Publications

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …