Pediatrics Commons^™

Therapeutic Phlebotomy Is Safe In Children With Sickle Cell Anaemia And Can Be Effective Treatment For Transfusional Iron Overload, B. Aygun, N. A. Mortier, K. Kesler, A. Lockhart, W. H. Schultz, A. R. Cohen, O. Alvarez, Z. R. Rogers, J. L. Kwiatkowski, R. E. Ware, +4 Additional Authors

Journal Articles

Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (-8.7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment.

Recurrent Gain Of Function Mutation In Calcium Channel Cacna1h Causes Early-Onset Hypertension With Primary Aldosteronism, U. I. Scholl, G. Stolting, C. Nelson-Williams, A. A. Vichot, M. Choi, E. Loring, M. L. Prasad, G. Goh, C. B. Sethna, R. P. Lifton, +11 Additional Authors

Journal Articles

Many Mendelian traits are likely unrecognized owing to absence of traditional segregation patterns in families due to causation by de novo mutations, incomplete penetrance, and/or variable expressivity. Genome-level sequencing can overcome these complications. Extreme childhood phenotypes are promising candidates for new Mendelian traits. One example is early onset hypertension, a rare form of a global cause of morbidity and mortality. We performed exome sequencing of 40 unrelated subjects with hypertension due to primary aldosteronism by age 10. Five subjects (12.5%) shared the identical, previously unidentified, heterozygous CACNA1H(M1549V) mutation. Two mutations were demonstrated to be de novo events, and all mutations …

Safety And Clinical Activity Of Elosulfase Alfa In Pediatric Patients With Morquio A Syndrome (Mucopolysaccharidosis Iva) Less Than 5 Years, S. A. Jones, M. Bialer, R. Parini, K. Martin, H. Wang, K. Yang, A. J. Shaywitz, P. Harmatz

Journal Articles

BACKGROUND: Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged >/=5 years. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients. METHODS: Fifteen Morquio A patients aged/kg/week for 52 weeks during the primary treatment phase of a phase II, open-label, multinational study. Primary endpoint was safety and tolerability, secondary endpoints were change in uKS and growth velocity over 52 weeks. RESULTS: All 15 patients completed the primary treatment phase. Six of 743 infusions (0.8%) administered led to adverse events (AEs) requiring infusion interruption …

Tat-Hsp70 Attenuates Experimental Lung Injury, M. M. Lyons, N. N. Raj, J. L. Chittams, L. Kilpatrick, C. S. Deutschman

Journal Articles

Sepsis, a poorly understood syndrome of disordered inflammation, is the leading cause of death in critically ill patients. Lung injury, in the form of acute respiratory distress syndrome (ARDS), is the most common form of organ injury in sepsis. The heat shock response, during which heat shock proteins (HSPs) are expressed, is an endogenous mechanism to protect cells from injury. We have found that the abundance of pulmonary HSP70 is not increased after cecal ligation and double puncture (CLP) in a rat model of sepsis-induced ARDS. Using the HIV-1 trans-activator of transcription (TAT) cell-penetrating protein, we enhanced HSP70 protein abundance …

A Self-Paced Oral Feeding System That Enhances Preterm Infants' Oral Feeding Skills, C. Lau, S. Fucile, R. J. Schanler

Journal Articles

AIM: Very low birth weight (VLBW) infants have difficulty transitioning to independent oral feeding, be they breast- or bottle-feeding. We developed a 'self-paced' feeding system that eliminates the natural presence of the positive hydrostatic pressure and internal vacuum build-up within a bottle during feeding. Such system enhanced these infants' oral feeding performance as monitored by overall transfer (OT; % ml taken/ml prescribed), rate of transfer (RT; ml/min over an entire feeding). This study hypothesizes that the improvements observed in these infants resulted from their ability to use more mature oral feeding skills (OFS). METHODS: 'Feeders and growers' born between 26-29 …

Therapeutic Hypothermia After Out-Of-Hospital Cardiac Arrest In Children, F. W. Moler, F. S. Silverstein, R. Holubkov, B. S. Slomine, J. R. Christensen, V. M. Nadkarni, K. L. Meert, C. L. Schleien, J. M. Dean, +35 Additional Authors

Journal Articles

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0 degrees C) or therapeutic normothermia (target temperature, 36.8 degrees C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a …

Use Of Serogroup B Meningococcal Vaccines In Persons Aged >= 10 Years At Increased Risk For Serogroup B Meningococcal Disease: Recommendations Of The Advisory Committee On Immunization Practices, 2015, T. Folaranmi, L. Rubin, S. W. Martin, M. Patel, J. R. Macneil

Journal Articles

No abstract provided.

Yellow Fever Vaccine Booster Doses: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. E. Staples, J. A. Bocchini, L. Rubin, M. Fischer

Journal Articles

No abstract provided.

Optical Measurement Of Skin Temperature In Mr-Hifu, Daniel Yang, Haydar Celik, Doug Wackerle, David Kinnaird, Avinash Eranki, Matthew E. Oetgen, Aerang Kim, Karun Sharma, Harry Kim, Peter Kim, Pavel Yarmolenko

Pediatrics Posters and Presentations

No abstract provided.

The Optimization Of Treatment Planning And Ablation Rate Improvements On Feasibility Of Pediatric Mr-Hifu Applications, Doug Wackerle, Haydar Celik, David Kinnaird, Daniel Yang, Avinash Eranki, Matthew E. Oetgen, Aerang Kim, Karun Sharma, Harry Kim, Peter Kim, Pavel Yarmolenko

Pediatrics Posters and Presentations

No abstract provided.

Improving Newborn Care Practices Through Home Visits: Lessons From Malawi, Nepal, Bangladesh, And Uganda., Deborah Sitrin, Tanya Guenther, Peter Waiswa, Sarah Namutamba, Gertrude Namazzi, Srijana Sharma, K. C. Ashish, Sayed Rubayet, Subrata Bhadra, Reuben Ligowe, Emmanuel Chimbalanga, Elizabeth Sewell, Kate Kerber, Allisyn Moran

Pediatrics Faculty Publications

Background: Nearly all newborn deaths occur in low- or middle-income countries. Many of these deaths could be prevented through promotion and provision of newborn care practices such as thermal care, early and exclusive breastfeeding, and hygienic cord care. Home visit programmes promoting these practices were piloted in Malawi, Nepal, Bangladesh, and Uganda.

Objective: This study assessed changes in selected newborn care practices over time in pilot programme areas in four countries and evaluated whether women who received home visits during pregnancy were more likely to report use of three key practices.

Design: Using data from cross-sectional surveys …

Percutaneous Mr Guided Direct Left Atrial Access To Deliver Large Interventional Devices, Toby Rogers, William Schenke, Jonathan R. Mazal, Merdim Sonmez, Ozgur Kocaturk, Kanishka Ratnayaka, Michael Hansen, Anthony Z. Faranesh, Robert J. Lederman

Pediatrics Faculty Publications

No abstract provided.

The Oral Bacterial Communities Of Children With Well-Controlled Hiv Infection And Without Hiv Infection., Brittany E. Goldberg, Emmanuel F. Mongodin, Cheron E. Jones, Michelle Chung, Claire M. Fraser, Anupama R. Tate, Steven L. Zeichner

Pediatrics Faculty Publications

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section …

Temporal Order Of Rnase Iiib And Loss-Of-Function Mutations During Development Determines Phenotype In Dicer1 Syndrome: A Unique Variant Of The Two-Hit Tumor Suppression Model [V1; Ref Status: Approved With Reservations 1, Http://F1000r.Es/5l9], Mark Brenneman, Amanda Field, Jiandong Yang, Gretchen Williams, Leslie A. Doros, Christopher T. Rossi, Heather A. Gordish-Dressman, D. Ashley Hill, Et Al.

Pediatrics Faculty Publications

Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over …

Β2-Adrenergic Receptor Promoter Haplotype Influences The Severity Of Acute Viral Respiratory Tract Infection During Infancy: A Prospective Cohort Study., Pingsheng Wu, Emma K. Larkin, Sara S Reiss, Kecia N Carroll, Marshall L. Summar, Patricia A Minton, +6 Additional Authors

Pediatrics Faculty Publications

BACKGROUND: Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections.

METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of …

Differential Expression Of The Nrf2-Linked Genes In Pediatric Septic Shock., Jocelyn R Grunwell, Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, +10 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock.

METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated …

Beyond Cd19: Opportunities For Future Development Of Targeted Immunotherapy In Pediatric Relapsed-Refractory Acute Leukemia., Haneen Shalabi, Anne Angiolillo, Terry J Fry

Pediatrics Faculty Publications

Chimeric antigen receptor (CAR) T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose-limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell acute lymphoblastic leukemia (ALL), this mode of therapy has become a very attractive option for these patients with high-risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia and potential therapeutic targets for additional high-risk populations, including T cell ALL, AML, and infant ALL.

Intracellular Cd24 Disrupts The Arf-Npm Interaction And Enables Mutational And Viral Oncogene-Mediated P53 Inactivation., Lizhong Wang, Runhua Liu, Peiying Ye, Chunshu Wong, Guo-Yun Chen, Penghui Zhou, +11 Additional Authors

Pediatrics Faculty Publications

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the …

Acute Glomerular Diseases In Children, Kanwal Kher

Pediatrics Faculty Publications

Glomerulonephritis [GN] is one of the common acquired pediatric renal disorders encountered in clinical practice. The clinical manifestations include gross or microscopic hematuria, proteinuria, and nephrotic syndrome. Renal dysfunction and hypertension may also be present in many patients. Etiopathogenesis of GN can be idiopathic in a large majority, while some may result from infections or known immune disorders. Several of these disorders are now believed to arise from dysfunctions of podocytes and are grouped under the heading of “podocytopathies”. This review focuses on the clinical manifestations and management of the common forms of acute GN encountered in children.

Genetic And Informatic Analyses Implicate Kif12 As A Candidate Gene Within The Mpkd2 Locus That Modulates Renal Cystic Disease Severity In The Cys1cpk Mouse., Michal Mrug, Juling Zhou, Chaozhe Yang, Bruce J Aronow, Xiangqin Cui, Trenton R Schoeb, Gene P Siegal, Bradley K Yoder, Lisa M. Guay-Woodford

Pediatrics Faculty Publications

We have previously mapped the interval on Chromosome 4 for a major polycystic kidney disease modifier (Mpkd) of the B6(Cg)-Cys1cpk/J mouse model of recessive polycystic kidney disease (PKD). Informatic analyses predicted that this interval contains at least three individual renal cystic disease severity-modulating loci (Mpkd1-3). In the current study, we provide further validation of these predicted effects using a congenic mouse line carrying the entire CAST/EiJ (CAST)-derived Mpkd1-3 interval on the C57BL/6J background. We have also generated a derivative congenic line with a refined CAST-derived Mpkd1-2 interval and demonstrated its dominantly-acting disease-modulating effects (e.g., 4.2-fold increase in total cyst area; …

Extraordinary Diversity Of Immune Response Proteins Among Sea Urchins: Nickel-Isolated Sp185/333 Proteins Show Broad Variations In Size And Charge., Lauren S. Sherman, Catherine S. Schrankel, Kristy J. Brown, L. Courtney Smith

Pediatrics Faculty Publications

Effective protection against pathogens requires the host to produce a wide range of immune effector proteins. The Sp185/333 gene family, which is expressed by the California purple sea urchin Strongylocentrotus purpuratus in response to bacterial infection, encodes a highly diverse repertoire of anti-pathogen proteins. A subset of these proteins can be isolated by affinity to metal ions based on multiple histidines, resulting in one to four bands of unique molecular weight on standard Western blots, which vary depending on the individual sea urchin. Two dimensional gel electrophoresis (2DE) of nickel-isolated protein samples followed by Western blot was employed to detect …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

Choledochal Cyst Mimicking Gallbladder With Stones In A Six-Year-Old With Right-Sided Abdominal Pain, R. Subramony, N. Kittisarapong, I. Barata, M. Nelson

Journal Articles

Choledochal cysts are rare but serious bile duct abnormalities are found in young children, usually during the first year of life.1 They require urgent surgical intervention due to the risk of developing cholangiocarcinoma.2 Clinicians should consider this diagnosis and perform a point-of-care ultrasound (POCUS) when a child presents to the emergency department (ED) with findings of jaundice, abdominal pain, and the presence of an abdominal mass. We present the case of a six-year-old child presenting only with abdominal pain upon arrival to our ED and was ultimately diagnosed by POCUS to have a choledochal cyst.

Effects Of Wharton's Jelly-Derived Mesenchymal Stem Cells On Neonatal Neutrophils, I. Khan, L. Zhang, M. Mohammed, F. E. Archer, J. Abukharmah, Z. Yuan, S. S. Rizvi, M. G. Melek, B. Weinberger, A. M. Vetrano, +2 Additional Authors

Journal Articles

BACKGROUND: Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils. METHODS: WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression …

The Erythroblastic Island As An Emerging Paradigm In The Anemia Of Inflammation, J. Hom, B. M. Dulmovits, N. Mohandas, L. Blanc

Journal Articles

Terminal erythroid differentiation occurs in the bone marrow, within specialized niches termed erythroblastic islands. These functional units consist of a macrophage surrounded by differentiating erythroblasts and have been described more than five decades ago, but their function in the pathophysiology of erythropoiesis has remained unclear until recently. Here we propose that the central macrophage in the erythroblastic island contributes to the pathophysiology of anemia of inflammation. After introducing erythropoiesis and the interactions between the erythroblasts and the central macrophage within the erythroblastic islands, we will discuss the immunophenotypic characterization of this specific subpopulation of macrophages. We will then integrate these …

Judging Quality Of Current Septic Shock Definitions And Criteria, M. Shankar-Hari, G. Bertolini, F. M. Brunkhorst, R. Bellomo, D. Annane, C. S. Deutschman, M. Singer

Journal Articles

Septic shock definitions are being revisited. We assess the feasibility, reliability, and validity characteristics of the current definitions and criteria of septic shock. Septic shock is conceptualised as cardiovascular dysfunction, tissue perfusion and cellular abnormalities caused by infection. Currently, for feasibility, septic shock is identified at the bedside by using either hypotension or a proxy for tissue perfusion/cellular abnormalities (e.g., hyperlactatemia). We propose that concurrent presence of cardiovascular dysfunction and perfusion/cellular abnormalities could improve validity of septic shock diagnosis, as we are more likely to identify a patient population with all elements of the illness concept. This epidemiological refinement should …

Mutations In Ddx3x Are A Common Cause Of Unexplained Intellectual Disability With Gender-Specific Effects On Wnt Signaling, L. Snijders Blok, E. Madsen, J. Juusola, C. Gilissen, D. Baralle, M. R. Reijnders, H. Venselaar, J. Fox, J. Mclaughlin, T. Kleefstra, +73 Additional Authors

Journal Articles

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common …

Obtaining Research Biopsies During Pediatric Colonoscopy: Safety And Adverse Events, J. Mait-Kaufman, S. Kahn, G. Tomer

Journal Articles

AIM: To investigate the safety profile of acquiring additional intestinal biopsies for research purposes in children undergoing a medically indicated colonoscopy. METHODS: A retrospective review of 122 pediatric patients who underwent colonoscopy over a 9 mo time period was completed. 38/122 participants consented to a research study in which 4 additional biopsies were obtained, in addition to routine biopsies. The outcomes after colonoscopy were measured in the research participants, and compared to 84 control participants who did not consent for the study. Groups were compared with regard to number of biopsies obtained, underlying diagnosis, and both serious and minor adverse …

Oral Feeding Assessment Predicts Length Of Hospital Stay In Late Preterm Infants, C. Lau, K. Bhat, D. Potak, R. J. Schanler

Journal Articles

BACKGROUND: When compared with term infants, late preterm (LP) infants have greater morbidity and mortality, longer hospital stay, and greater rate of hospital readmission. Oral feeding difficulty is one of the prominent reasons for delayed discharge in LP infants. OBJECTIVE: To identify the maturity levels of LP infants' oral feeding skills (OFS) at the time of their first oral feeding and to determine the relationship between OFS maturity levels and length of hospital stay. METHODS: OFS was assessed in 48 LP infants born between 340/7 and 356/7 weeks gestational age at the time of their first oral feeding within 24 …

Risk Factors Associated With Intracranial Hemorrhage In Neonates With Persistent Pulmonary Hypertension On Ecmo, S. Doymaz, M. Zinger, T. Sweberg

Journal Articles

BACKGROUND: Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN. METHODS: A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children's hospital. …