Pediatrics Commons^™

Going Back In Time: Increasing Penicillin Susceptibility Among Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Jesus G Vallejo, Mary Boyle, Kristina G Hulten, Sheldon L Kaplan, Stephanie A Fritz

Faculty, Staff and Students Publications

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ …

Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu

Faculty, Staff and Students Publications

Brain-heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which …

The Safety Of Appropriate Use Of Over-The-Counter Proton Pump Inhibitors: An Evidence-Based Review And Delphi Consensus, Wilfredo De Jesús-Rojas, Jesús Meléndez-Montañez, José Muñiz-Hernández, André Marra-Nazario, Francisco Alvarado-Huerta, Arnaldo Santos-López, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

Yoga And Mindfulness For Social-Emotional Development And Resilience In 3–5 Year-Old Children: Non-Randomized, Controlled Intervention, Alessandra N. Bazzano, Yaoyao Sun, Yuanhao Zu, Julia M. Fleckman, Emma A. Blackson, Tejal Patel, Angie Shorty-Belisle, Keith H. Liederman, Cody Roi

School of Medicine Faculty Publications

Background: Early childhood is the key life course period for development of social-emotional skills, providing the foundation for school readiness and resilience in later life. Age-appropriate yoga and mindfulness programs may contribute to the development of critical skills in children. Young children from minoritized communities that face structural racism and health disparities may benefit from programs that support social-emotional development and contribute to future academic success. Systematic reviews of yoga interventions for young children have indicated the potential for effectiveness in supporting social-emotional development, executive function, and physical activity. However, studies of yoga and mindfulness with non-White children are sparse …

Efficacy Of Eltrombopag With Immunosuppressive Therapy For Children With Acquired Aplastic Anemia, Yufei Zhao, Wenrui Yang, Xin Zhao, Xiangrong Hu, Jing Hu, Xu Liu, Jianping Li, Lei Ye, Youzhen Xiong, Yang Yang, Baohang Zhang, Xiaoxia Li, Xiawan Yang, Yimeng Shi, Guangxin Peng, Yuan Li, Huihui Fan, Kang Zhou, Liping Jing, Li Zhang, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial.

METHODS: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) …

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …

The Impact Of Covid-19 On Pediatric Cardiac Arrest Outcomes: A Systematic Review And Meta-Analysis, Alla Navolokina, Jacek Smereka, Bernd W Böttiger, Michal Pruc, Raúl Juárez-Vela, Mansur Rahnama-Hezavah, Zubaid Rafique, Frank W Peacock, Kamil Safiejko, Lukasz Szarpak

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic, required the donning of personal protective equipment during clinical contact, and continues to be a significant worldwide public health concern. Pediatric cardiac arrest is a rare but critical condition with a high mortality rate, the outcomes of which may be negatively affected by donning personal protective equipment. The aim of this study is to perform a systematic review and meta-analysis of the impact of the COVID-19 pandemic on pediatric cardiac arrest outcomes. We conducted a systematic review with meta-analysis in the following databases: PubMed, EMBASE, Scopus, Web of Science, …

Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao

Faculty, Staff and Students Publications

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, …

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in …

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

BACKGROUND: Single-cell omics technology is rapidly developing to measure the epigenome, genome, and transcriptome across a range of cell types. However, it is still challenging to integrate omics data from different modalities. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by using graph-based contrastive loss.

RESULTS: By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitope data. Further evaluation demonstrated our model's unique ability to remove the batch …

Utility Of Computed Tomography In Diagnosis Of A Patent Ductus Arteriosus In Pulmonary Artery Endarteritis, Anneliese J Grewing, Betul Yilmaz Furtun, Melissa K Webb

Faculty, Staff and Students Publications

A 15-year-old patient with infective endarteritis had a pulmonary artery vegetation but no ductus arteriosus on echocardiogram. Computed tomography scan revealed a closed ductus that became patent after antibiotics and anticoagulation. Infective endarteritis should be considered in patients with a pulmonary artery vegetation even if no ductus is seen on echocardiogram. (Level of Difficulty: Intermediate.)

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

A Story Of Hope: How A Community Project Is Transforming The Lives Of Filipino Children With Intellectual And Developmental Disabilities, Lance Vincent C. Sese, Ma Celina L. Guillermo

Ateneo School of Medicine and Public Health Publications

The issue of social inequality became more prevalent during the pandemic and with it, the call for preferential option toward the vulnerable. 1 Not only do we protect them from sickness and death, but we are also called to improve their quality of life. Thus, it is imperative that in this call for inclusivity, we address the gap, one group at a time—for example, children with special needs. The project discussed in this perspective article exemplifies the importance of collaboration in bridging the gap to create a more holistic environment for Filipino children with special needs. This article then serves …

School-Based Intervention Impacts Availability Of Vegetables And Beverages In Participants’ Homes, Erin A Hudson, Marissa Burgermaster, Sophia M Isis, Matthew R Jeans, Sarvenaz Vandyousefi, Matthew J Landry, Rebecca Seguin-Fowler, Joya Chandra, Jaimie Davis

Faculty, Staff and Student Publications

As rates of metabolic syndrome rise, children consume too few vegetables and too much added sugar. Because children tend to eat what is available at home, the home environment plays a key role in shaping dietary habits. This secondary analysis evaluated the effects of a school-based gardening, cooking, and nutrition education intervention (TX Sprouts) compared to control on the availability of vegetables, fruit juice, and sugar-sweetened beverages (SSBs) at home. In the TX Sprouts cluster-randomized trial, 16 schools were randomized to TX Sprouts (

Characteristics Of Pediatric Covid-19 Infections And The Impact Of Influenza And Covid-19 Vaccinations During The First Two Years Of The Pandemic, Mahmoud Ali, Lynette Phillips, David C Kaelber, Hulya Bukulmez

Faculty, Staff and Student Publications

The data regarding the demographics of SARS-CoV-2 in the pediatric population has been published based on several single-center experiences or on metanalyses over short time frames. This article reports data on the demographics of pediatric patients with COVID-19 on a global scale using the TriNetX COVID-19 Research Network. In addition, we examined the risk of COVID-19 infection in relation to the body mass index (BMI) category and the protective value of influenza and COVID-19 immunization against COVID-19 infection. The incidence of COVID-19 infection was higher in the younger age group (≤6 years old), but no gender differences. The incidence of …

Characteristics Of Type 2 Diabetes In Female And Male Youth, Beatriz Castillo Rodriguez, Marcela Astudillo, Mustafa Tosur, Ahmad Rafaey, Siripoom Mckay, Fida Bacha, Ashok Balasubramanyam, Maria J Redondo

Faculty, Staff and Students Publications

The incidence of type 2 diabetes in children is rising and carries a worse prognosis than in adults. The influence of sex on pediatric type 2 diabetes outcomes has not been well investigated. We studied 715 youth with type 2 diabetes diagnosed at a median age of 13.7 years and compared sex differences in demographic, clinical, and laboratory characteristics within the first year of diagnosis. Females diagnosed with type 2 diabetes were younger and at a higher stage of pubertal development than males, yet presented with lower A1Cs, a lower prevalence of diabetic ketoacidosis, and higher HDL cholesterol levels.

Extracorporeal Membrane Oxygenation Cannulation Timing In The Pediatric Myocarditis Population: An Exploratory Analysis From The Extracorporeal Life Support Organization Registry, Maria E Gutierrez, Marc Anders, Danielle Guffey, Susan W Denfield, Shriprasad R Deshpande, Satish K Rajagopal, Ravi R Thiagarajan, Peta M A Alexander, Javier J Lasa

Faculty, Staff and Students Publications

Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population.

DESIGN: Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation.

SETTING AND SUBJECTS: The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 …

Ems Administration Of Systemic Corticosteroids To Pediatric Asthma Patients: An Analysis By Severity And Transport Interval, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer Fishe

Faculty, Staff and Students Publications

INTRODUCTION: Pediatric asthma exacerbations are a common cause of emergency medical services (EMS) encounters. Bronchodilators and systemic corticosteroids are mainstays of asthma exacerbation therapy, yet data on the efficacy of EMS administration of systemic corticosteroids are mixed. This study's objective was to assess the association between EMS administration of systemic corticosteroids to pediatric asthma patients on hospital admission rates based on asthma exacerbation severity and EMS transport intervals.

METHODS: This is a sub-analysis of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI AS ODT). EASI AS ODT is a non-randomized, stepped wedge, observational study …

Inotropic Score And Vasoactive Inotropic Score As Predictors Of Outcomes In Congenital Diaphragmatic Hernia: A Single Center Retrospective Study, Srirupa Hari Gopal, Cynthia L Toy, Morcos Hanna, Betul Yilmaz Furtun, Joseph L Hagan, Ahmed A Nassr, Caraciolo J Fernandes, Sundeep Keswani, Sharada H Gowda

Faculty, Staff and Students Publications

BACKGROUND: Neonates with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction. These neonates frequently require vasoactive support and are at high risk for mortality and morbidity, including prolonged ventilator support, need for extracorporeal membrane oxygenation (ECMO), prolonged length of stay, and need for tracheostomy. However, identifying which infants are at increased risk can be challenging. In this study, we sought to investigate the utility of the inotropic score (IS) and vasoactive inotropic score (VIS) as tools to predict significant clinical outcomes and overall survival in patients with CDH. Additionally, we evaluated the …

Beyond Breathless: Unravelling The Enigma Of Pulmonary Arteriovenous Malformations, Sri Mounya Jampala, Jagadish Kumar K Dr., Manjunath V G, Nandish H R

Digital Journal of Clinical Medicine

Pulmonary Arteriovenous Malformations (AVMs) are abnormal connections between the pulmonary arteries and veins, leading to a direct shunting of blood without passing through the normal capillary bed. These AVMs can be associated with a rare genetic disorder called Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome. HHT is an autosomal dominant disorder characterized by the development of fragile telangiectasias in various organs, including the skin and mucous membranes. These telangiectasias are prone to bleeding, leading to recurrent nosebleeds and mucocutaneous bleeding. In patients with HHT, the most common site of AVMs is in the lungs. Pulmonary AVMs can cause …

Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh

Faculty, Staff and Student Publications

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and an unappreciated contributor to child mortality in low- and middle-income countries where the diagnosis may be difficult. There is little information about the prevalence of CDI among infants, children, and adolescents in Africa. Using a cross-sectional design, seventy-six samples were collected from pediatric patients presenting with diarrhea, including infants (≤ 2 years old), children (2-12 years), and adolescents (13 ≤17 years) from three hospitals between January and December 2019. Demographic data, medical history, and prior antibiotic use were recorded. Toxigenic culture and PCR were used to detect and …

Hypofibrinogenemia Following Injury In 186 Children And Adolescents: Identification Of The Phenotype, Current Outcomes, And Potential For Intervention, Justin Gerard, Jan-Michael Van Gent, Jessica Cardenas, Christian Gage, David E Meyer, Charles Cox, Charles E Wade, Bryan A Cotton

Faculty, Staff and Student Publications

OBJECTIVES: Recent studies evaluating fibrinogen replacement in trauma, along with newly available fibrinogen-based products, has led to an increase in debate on where products such as cryoprecipitate belong in our resuscitation strategies. We set out to define the phenotype and outcomes of those with hypofibrinogenemia and evaluate whether fibrinogen replacement should have a role in the initial administration of massive transfusion.

METHODS: All patients/17-4/21 were reviewed. We then evaluated all patients who received emergency-release and massive transfusion protocol (MTP) products. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen(r-TEG) angleHYPOFIB, the impact on outcomes, and whether early replacement improved mortality. …

Vital Signs For Pediatric Health: Chronic Absenteeism, Sara B Johnson, Anne Edwards, Tina Cheng, Kelly J Kelleher, Jennifer Kaminski, Erin G Fox

Faculty, Staff and Student Publications

No abstract provided.

An Individual Data-Driven Virtual Resection Model Based On Epileptic Network Dynamics In Children With Intractable Epilepsy: A Magnetoencephalography Interictal Activity Application, Pablo Cuesta, Ricardo Bruña, Ekta Shah, Christopher Laohathai, Stephanie Garcia-Tarodo, Michael Funke, Gretchen Von Allmen, Fernando Maestú

Faculty, Staff and Student Publications

Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30-70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient's magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual …

Comparison Of Two Lipid Emulsions On The Incidence Of Parenteral Nutrition Associated Cholestasis In Neonates, Joy Greenberg, Mamta Naik, John Chapman, Allison Davidson, Essam Imseis

Faculty, Staff and Student Publications

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE.

METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were …

Use Of Elamipretide In Patients Assigned Treatment In The Compassionate Use Program: Case Series In Pediatric Patients With Rare Orphan Diseases, Mary Kay Koenig, Sam Nick Russo, Kim L Mcbride, Hans Tomas Bjornsson, Brynja Bjork Gunnarsdottir, Amy Goldstein, Scott A Falk

Faculty, Staff and Student Publications

Several mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA-approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide …

National Cross-Sectional Study On Cost Consciousness, Cost Accuracy, And National Medical Waste Reduction Initiative Knowledge Among Pediatric Hospitalists In The United States, Benjamin C Lee, Matt Hall, Ladan Agharokh, Andrew G Yu, Kavita Parikh, Samir S Shah

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVE: Despite initiatives to reduce waste and spending, there is a gap in physician knowledge regarding the cost of commonly ordered items. We examined the relationship between pediatric hospitalists' knowledge of national medical waste reduction initiatives, self-reported level of cost-consciousness (the degree in which cost affects practice), and cost accuracy (how close an estimate is to its hospital cost) at a national level.

METHODS: This cross-sectional study used a national, online survey sent to hospitalists at 49 children's hospitals to assess their knowledge of national medical waste reduction initiatives, self-reported cost consciousness, and cost estimates for commonly ordered laboratory studies, …

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …

Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung

Faculty, Staff and Students Publications

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue …