Internal Medicine Commons^™

Meta-Analysis On Sex Differences In Mortality And Neurodevelopment In Congenital Heart Defects, Alyssa K Crain, Zhia N Lim, Chloe J Sarfatis, Magela Arias, Travis Holder, Alvaro G Moreira, Antonio F Corno, Tina O Findley

Faculty, Staff and Student Publications

Given the increasing survival rates among congenital heart disease (CHD) patients and the growing emphasis on their quality of life, there is a need to comprehensively assess the impact of surgical interventions on neurodevelopmental outcomes. With increasing awareness in sex-related disparities in CHD, there is a need to explore potential differences in surgical mortality and neurodevelopmental outcomes between male and female patients. In this systematic review, we adhered to PRISMA guidelines and PROSPERO registration (#CRD42021225610). Articles published from 2015 to 2021 were searched using MeSH descriptors in three major databases (MEDLINE Ovid, Elsevier Embase, and Cochrane Library). Study selection criteria …

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 …

Social Vulnerability And Sickle Cell Disease Mortality In The Us, Jia Yi Tan, Boon Jian San, Yong-Hao Yeo, Kok Hoe Chan, Hamid S Shaaban, Daniel E Ezekwudo, Modupe Idowu

Faculty, Staff and Student Publications

Importance: Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies.

Objective: To investigate the association of SDOH with SCD mortality rates from 2016 to 2020.

Design, setting, and participants: This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into …

Patient And Family Contributions To Improve The Diagnostic Process Through The Ourdx Electronic Health Record Tool: A Mixed Method Analysis, Sigall K Bell, Kendall Harcourt, Joe Dong, Catherine Desroches, Nicholas J Hart, Stephen K Liu, Long Ngo, Eric J Thomas, Fabienne C Bourgeois

Faculty, Staff and Student Publications

Background: Accurate and timely diagnosis relies on sharing perspectives among team members and avoiding information asymmetries. Patients/Families hold unique diagnostic process (DxP) information, including knowledge of diagnostic safety blindspots-information that patients/families know, but may be invisible to clinicians. To improve information sharing, we co-developed with patients/families an online tool called 'Our Diagnosis (OurDX)'. We aimed to characterise patient/family contributions in OurDX and how they differed between individuals with and without diagnostic concerns.

Method: We implemented OurDX in two academic organisations serving patients/families living with chronic conditions in three subspecialty clinics and one primary care clinic. Prior to each visit, patients/families …

Dual Inhibition Of The Trka And Jak2 Pathways Using Entrectinib And Pacritinib Suppresses The Growth And Metastasis Of Her2-Positive And Triple-Negative Breast Cancers, Angelina T Regua, Shivani Bindal, Mariana K Najjar, Chuling Zhuang, Munazza Khan, Austin B J Arrigo, Anneliese O Gonzalez, Xinhai R Zhang, Jay-Jiguang Zhu, Kounosuke Watabe, Hui-Wen Lo

Faculty, Staff and Student Publications

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness …

Bispecific Antibodies And Autologous Chimeric Antigen Receptor T Cell Therapies For Treatment Of Hematological Malignancies, Samer Al Hadidi, Helen E Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset …

Ruptured Infectious Pseudoaneurysm Of The Common Carotid Artery In A 14-Year-Old Girl. Management In The Dr Congo, Alphonse Nzomvuama, Jean Jacques Kalongo, Blondel Bayenekene, Stéphane Yanda, M. Jacques Nsuami

School of Medicine Faculty Publications

The infectious pseudoaneurysm of the common carotid artery is a rare observation in children. We present a case of ruptured infectious common carotid aneurysm in a 14-year-old girl managed in the Democratic Republic of Congo. We performed an arterial reconstruction with a saphenous vein patch. Post-operative course was simple. The patient was discharged from the hospital at post-operative day 15. She was doing well and had returned to school. Rupture of an infectious pseudoaneurysm of the common carotid artery constitutes a serious, life-threatening accident. As we have shown in this case report, its management with successful results is indeed possible, …

Improvements In Appropriate Placement Of Dental Sealants After Implementation Of A Clinical Decision Support System, Joanna Mullins, Ryan Brandon, Nicholas Skourtes, Elsbeth Kalenderian, Muhammad Walji

Faculty, Staff and Student Publications

BACKGROUND: Dental sealants are effective for the prevention of caries in children at elevated risk levels, and increasing the proportion of children and adolescents who have dental sealants on 1 or more molars is a Healthy People 2030 objective. Electronic health record (EHR)-based clinical decision support systems (CDSSs) have the ability to improve patient care. A dental quality measure related to dental sealant placement for children at elevated risk of caries was targeted for improvement using a CDSS.

METHODS: A validated dental quality measure was adapted to assess a patient's need for dental sealant placement. A CDSS was implemented to …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Prognostic Values Of Serum Lactate-To-Bicarbonate Ratio And Lactate For Predicting 28-Day In-Hospital Mortality In Children With Dengue Shock Syndrome, Thanh Nguyen Tat, Nhu Vo Hoang-Thien, Dat Nguyen Tat, Phuc Hoang Nguyen, Lien Thi Ho, Duong Hung Doan, Dung Tuan Phan, Yen Nguyen-Hoang Duong, Truc Huynh Nguyen, Tuyet Kim Nguyen, Ha Thi-Thu Dinh, Thuy Thi-Diem Dinh, Anh Thi-Mai Pham, Viet Do Chau, Tung Huu Trinh, Luan Vo Thanh

Faculty, Staff and Student Publications

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of …

Inaccurate Diagnosis Of Diabetes Type In Youth: Prevalence, Characteristics, And Implications, Mustafa Tosur, Xiaofan Huang, Audrey S Inglis, Rebecca Schneider Aguirre, Maria J Redondo

Faculty, Staff and Students Publications

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), …

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …

Diabetes Study Of Children Of Diverse Ethnicity And Race: Study Design, Maria J Redondo, Kylie K Harrall, Deborah H Glueck, Mustafa Tosur, Serife Uysal, Andrew Muir, Elizabeth G Atkinson, Melanie R Shapiro, Liping Yu, William E Winter, Michael Weedon, Todd M Brusko, Richard Oram, Kendra Vehik, William Hagopian, Mark A Atkinson, Dana Dabelea, Discover Study Group

Faculty, Staff and Students Publications

AIMS: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)-supported multicenter, prospective, observational study that enrols children and adolescents with non-secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth.

MATERIALS AND METHODS: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on …

Rationale And Design Of The Nephrotic Syndrome Study Network (Neptune) Match In Glomerular Diseases: Designing The Right Trial For The Right Patient, Today, Howard Trachtman, Hailey Desmond, Amanda L Williams, Laura H Mariani, Sean Eddy, Wenjun Ju, Laura Barisoni, Heather K Ascani, Wendy R Uhlmann, Cathie Spino, Lawrence B Holzman, John R Sedor, Crystal Gadegbeku, Lalita Subramanian, Chrysta C Lienczewski, Tina Manieri, Scott J Roberts, Debbie S Gipson, Matthias Kretzler, Neptune Investigators

Faculty, Staff and Student Publications

Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we …

What's Going Well: A Qualitative Analysis Of Positive Patient And Family Feedback In The Context Of The Diagnostic Process, Stephen K Liu, Fabienne Bourgeois, Joe Dong, Kendall Harcourt, Elizabeth Lowe, Liz Salmi, Eric J Thomas, Natalie Riblet, Sigall K Bell

Faculty, Staff and Student Publications

OBJECTIVES: Accurate and timely diagnosis relies on close collaboration between patients/families and clinicians. Just as patients have unique insights into diagnostic breakdowns, positive patient feedback may also generate broader perspectives on what constitutes a "good" diagnostic process (DxP).

METHODS: We evaluated patient/family feedback on "what's going well" as part of an online pre-visit survey designed to engage patients/families in the DxP. Patients/families living with chronic conditions with visits in three urban pediatric subspecialty clinics (site 1) and one rural adult primary care clinic (site 2) were invited to complete the survey between December 2020 and March 2022. We adapted the …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Outcomes Of Simultaneous Lengthening And Acl Reconstruction In Fibular Hemimelia: A Retrospective Case Series, Bradley Reeves, Brennan Roper, Reba Salton, Ava Baumann, Radomir Dimovski, Nancy Hadley-Miller, Jay Albright

Faculty, Staff and Student Publications

BACKGROUND: Fibular hemimelia is the most common congenital long bone deficiency. It is often associated with femoral and tibial deficiencies which result in a clinically evident leg length discrepancy. The primary soft tissue concern is ACL/PCL deficiency. If treatment includes bony lengthening, joint stability is imperative to avoid complications. In this study, we detail a novel technique for long bone lengthening and ACL reconstruction in a single, cohesive surgery. This consolidates the need for multiple procedures and offers improved limb length symmetry and knee stability for this patient population. Clinical outcomes of pediatric patients with hemimelia who underwent either femoral …

Ispad Clinical Practice Consensus Guidelines 2024: Screening, Staging, And Strategies To Preserve Beta-Cell Function In Children And Adolescents With Type 1 Diabetes, Michael J Haller, Kirstine J Bell, Rachel E J Besser, Kristina Casteels, Jenny J Couper, Maria E Craig, Helena Elding Larsson, Laura Jacobsen, Karin Lange, Tal Oron, Emily K Sims, Cate Speake, Mustafa Tosur, Francesca Ulivi, Anette-G Ziegler, Diane K Wherrett, M Loredana Marcovecchio

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 …

High Prevalence Of A-Β+ Ketosis-Prone Diabetes In Children With Type 2 Diabetes And Diabetic Ketoacidosis At Diagnosis: Evidence From The Rare And Atypical Diabetes Network (Radiant), Elizabeth Kubota-Mishra, Xiaofan Huang, Charles G Minard, Marcela Astudillo, Ahmad Refaey, Graciela Montes, Stephanie Sisley, Nalini Ram, William E Winter, Rochelle N Naylor, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur, Radiant Study Group

Faculty, Staff and Students Publications

BACKGROUND:A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at “T2D” onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort.

METHODS: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the …

Pediatric Endocrinology Milestones 20-Guide To Their Implementation, Cara V Tillotson, Imen Becetti, Katherine Hwu, Laura Page, Sowmya Krishnan, Dianne Stafford, Takara Stanley, Patricia Vuguin, Jennifer M Barker

Faculty, Staff and Students Publications

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate …

Set-Pp2a Complex As A New Therapeutic Target In Kmt2a (Mll) Rearranged Aml, Antonella Di Mambro, Yoana Arroyo-Berdugo, Tiziana Fioretti, Michael Randles, Luca Cozzuto, Vinothini Rajeeve, Armando Cevenini, Michael J Austin, Gabriella Esposito, Julia Ponomarenko, Claire M Lucas, Pedro Cutillas, John Gribben, Owen Williams, Yolanda Calle, Bela Patel, Maria Teresa Esposito

Faculty, Staff and Student Publications

KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. …

Initial Development Of Tools To Identify Child Abuse And Neglect In Pediatric Primary Care, Rochelle F Hanson, Vivienne Zhu, Funlola Are, Hannah Espeleta, Elizabeth Wallis, Paul Heider, Marin Kautz, Leslie Lenert

Faculty, Staff and Student Publications

BACKGROUND: Child abuse and neglect (CAN) is prevalent, associated with long-term adversities, and often undetected. Primary care settings offer a unique opportunity to identify CAN and facilitate referrals, when warranted. Electronic health records (EHR) contain extensive information to support healthcare decisions, yet time constraints preclude most providers from thorough EHR reviews that could indicate CAN. Strategies that summarize EHR data to identify CAN and convey this to providers has potential to mitigate CAN-related sequelae. This study used expert review/consensus and Natural Language Processing (NLP) to develop and test a lexicon to characterize children who have experienced or are at risk …

Partnering With Patients And Families To Improve Diagnostic Safety Through The Ourdx Tool: Effects Of Race, Ethnicity, And Language Preference, Fabienne C Bourgeois, Nicholas J Hart, Zhiyong Dong, Long H Ngo, Catherine M Desroches, Eric J Thomas, Sigall K Bell

Faculty, Staff and Student Publications

BACKGROUND: Patients and families at risk for health disparities may also be at higher risk for diagnostic errors but less likely to report them.

OBJECTIVES: This study aimed to explore differences in race, ethnicity, and language preference associated with patient and family contributions and concerns using an electronic previsit tool designed to engage patients and families in the diagnostic process (DxP).

METHODS: Cross-sectional study of 5,731 patients and families presenting to three subspecialty clinics at an urban pediatric hospital May to December 2021 who completed a previsit tool, codeveloped and tested with patients and families. Prior to each visit, patients/families …

Plasma Amino Acid Signatures Define Types Of Pediatric Diabetes, Mustafa Tosur, Jean W Hsu, Saima Deen, Xiaofan Huang, Danielle Guffey, Serife Uysal, Marcela Astudillo, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D.

METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n …

Rare Variants In Ano1, Encoding A Calcium-Activated Chloride Channel, Predispose To Moyamoya Disease, Amélie Pinard, Wenlei Ye, Stuart M Fraser, Jill A Rosenfeld, Pavel Pichurin, Scott E Hickey, Dongchuan Guo, Alana C Cecchi, Maura L Boerio, Stéphanie Guey, Chaker Aloui, Kwanghyuk Lee, Markus Kraemer, Saleh Omar Alyemni, Michael J Bamshad, Deborah A Nickerson, Elisabeth Tournier-Lasserve, Shozeb Haider, Sheng Chih Jin, Edward R Smith, Kristopher T Kahle, Lily Yeh Jan, Mu He, Dianna M Milewicz

Faculty, Staff and Student Publications

Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses …

Effective Methods For Bulk Rna-Seq Deconvolution Using Scnrna-Seq Transcriptomes, Francisco Avila Cobos, Mohammad Javad Najaf Panah, Jessica Epps, Xiaochen Long, Tsz-Kwong Man, Hua-Sheng Chiu, Elad Chomsky, Evgeny Kiner, Michael J Krueger, Diego Di Bernardo, Luis Voloch, Jan Molenaar, Sander R Van Hooff, Frank Westermann, Selina Jansky, Michele L Redell, Pieter Mestdagh, Pavel Sumazin

Faculty, Staff and Students Publications

Background: RNA profiling technologies at single-cell resolutions, including single-cell and single-nuclei RNA sequencing (scRNA-seq and snRNA-seq, scnRNA-seq for short), can help characterize the composition of tissues and reveal cells that influence key functions in both healthy and disease tissues. However, the use of these technologies is operationally challenging because of high costs and stringent sample-collection requirements. Computational deconvolution methods that infer the composition of bulk-profiled samples using scnRNA-seq-characterized cell types can broaden scnRNA-seq applications, but their effectiveness remains controversial.

Results: We produced the first systematic evaluation of deconvolution methods on datasets with either known or scnRNA-seq-estimated compositions. Our analyses revealed …

Creating A Data Dictionary For Pediatric Autonomic Disorders, Jeffrey R Boris, Hasan Abdallah, Shelley Ahrens, Gisela Chelimsky, Thomas C Chelimsky, Philip R Fischer, John E Fortunato, Raewyn Gavin, Janice L Gilden, Renato Gonik, Blair P Grubb, Kelsey M Klaas, Erin Marriott, Lauren E Marsillio, Marvin S Medow, Lucy Norcliffe-Kaufmann, Mohammed T Numan, Erin Olufs, Laura A Pace, Paul T Pianosi, Pippa Simpson, Julian M Stewart, Sally Tarbell, Natalie R Van Waning, Debra E Weese-Mayer

Faculty, Staff and Student Publications

PURPOSE: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders.

METHODS: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which …

Heart And Timi Scores Predict Severe Coronary Atherosclerosis In Patients With End-Stage Renal Disease, Trishna B Parikh, Moez Aziz, Samuel P Mackoff, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Objectives History, EKG, age, risk factors, and troponin (HEART) and thrombolysis in myocardial infarction (TIMI) risk calculators have been validated to predict the risk of subsequent acute coronary syndromes and in some studies, severe coronary atherosclerosis in patients with a concerning clinical history. Their performance in patients with end-stage renal disease (ESRD), a population with a high pretest probability for the condition, is unknown. We aimed to determine whether HEART and TIMI scores can predict severe coronary atherosclerosis in patients with end-stage renal disease (ESRD). Methods A single-center retrospective cohort of admitted patients aged 18 years or older with ESRD …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Cord Blood Transplantation For Nonmalignant Disorders: Early Functional Immunity And High Survival, Caridad Martinez, Paibel Aguayo-Hiraldo, Natalia Chaimowitz, Lisa Forbes, Nicholas Rider, Sarah Nicholas, Filiz Seeborg, Javier Chinen, Ivan Chinn, Carla Davis, Howard Roseblatt, Lenora Noroski, Bilal Omer, Tami John, Khaled Yassine, Swati Naik, John Craddock, Saleh Bhar, Carl Allen, Nabil Ahmed, Ghadir Sasa, David Steffin, Erin Doherty, Anil George, Baheyeldin Salem, Brian Friend, Meenakshi Hegde, Malcolm K Brenner, Helen E Heslop, Ann Leen, Amanda Peña, Mengfen Wu, I Celine Hanson, Robert A Krance

Faculty, Staff and Students Publications

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients …