The Childrens Hospital Of Philadelphia

Philadelphia, PA, United States

The Childrens Hospital Of Philadelphia

Philadelphia, PA, United States

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Kestenbaum L.A.,The Childrens Hospital Of Philadelphia | Feemster K.A.,University of Pennsylvania
Pediatric Annals | Year: 2015

In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as “vaccine hesitant.” This phenomenon has developed due to the confluence of multiple social, cultural, political, and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. © SLACK Incorporated.

Law C.,The Childrens Hospital Of Philadelphia | Raffini L.,University of Pennsylvania
Pediatric Drugs | Year: 2015

Increasing thrombotic complications in children with complex medication conditions have led to more widespread use of anticoagulants [Raffini et al. in Pediatrics 124(4):1001–8, 2009]. While current guidelines for the management of antithrombotic therapy in neonates and children exist, they are based on low- and very low-quality evidence [Monagle et al. in Chest 141(2 Suppl):e737–801S, 2012]. Despite numerous differences, current anticoagulation practice is largely extrapolated from adult studies. This is sub-optimal, particularly in neonates who have a rapidly evolving hemostatic system. The majority of pediatric patients have underlying medical conditions that may significantly influence drug choice and bleeding risk. This article reviews the use of anticoagulants in children with thrombosis, focusing on practical aspects such as dosing, monitoring, and complications. Low molecular weight heparin has become the preferred anticoagulant in children, although unfractionated heparin and warfarin remain frequently used. Other anticoagulants, including fondaparinux, direct thrombin inhibitors, and the newer target-specific oral anticoagulants are also discussed. Given the many unique challenges surrounding the use of anticoagulants in children, pediatric hospitals should have written practice guidelines as well as experienced providers to care for children with thrombosis. This is an evolving field, and further studies of the use of anticoagulants in neonates and children are greatly needed to help optimize care. © 2015, Springer International Publishing Switzerland.

Victoria T.,The Childrens Hospital Of Philadelphia | Andronikou S.,University of Witwatersrand
Pediatric Radiology | Year: 2014

Background: A pattern of abnormal signal at fetal MRI may be seen in the setting of primary or secondary congenital lymphangiectasia, manifested as a heterogeneous appearance of the lung parenchyma and the presence of subtle T2-hyperintense branching tubular structures that emanate from the hila. We have named this pattern the nutmeg lung.Objective: We describe the nutmeg lung appearance seen in fetal MRI scans, with discussion of possible etiologies and outcomes in a series of eight fetuses.Materials and methods: We retrospectively reviewed imaging from a database of patients demonstrating features of nutmeg lung on fetal MRI. Medical records were used to determine the postnatal diagnosis, clinical course and outcome.Results: Among the eight fetal cases of nutmeg lung, two had postnatal confirmation of primary lymphangiectasia and the remaining six had secondary lymphangiectasia, presumably secondary to congenital cardiac anomalies. There were various-size pleural effusions in all cases. Only one of the cases demonstrated hydrops fetalis.Conclusion: We present the description of the nutmeg lung sign on fetal MRI as T2-hyperintense heterogeneous lungs with fluid-filled, serpiginous branching structures that extend from the pulmonary hila to the periphery of the lung, often accompanied by pleural effusions. The sign denotes findings of primary or secondary lymphangiectasia. Findings of secondary lymphangiectasia in our series were a result of cardiac insufficiency. Recognizing this sign might be helpful in the diagnostic algorithm of the fetus with abnormal lung parenchyma. © 2014, Springer-Verlag Berlin Heidelberg.

Refakis C.A.,The Childrens Hospital Of Philadelphia
Journal of Pediatric Orthopaedics | Year: 2016

BACKGROUND:: Although many studies have separately investigated the treatment of developmental dysplasia of the hip and spastic hip disease, little data exist regarding the treatment of infants with dislocated hips and underlying spasticity. The purpose of this study was to review our results after the surgical treatment of these infants. METHODS:: We retrospectively reviewed all children below 3 years of age who underwent hip reconstruction for dislocated hips in the setting of cerebral palsy or other spastic/high-tone neuromuscular disease. Medical records were reviewed for clinical data including treatment course, complications, and need for further surgery. Preoperative and postoperative radiographs were used to determine International Hip Dysplasia Institute (IHDI) grade of dislocation, acetabular index, migration percentage, and presence of avascular necrosis according to the Salter criteria. RESULTS:: Eleven patients with 15 hips met our inclusion criteria with a mean age of 20±8 (range, 6 to 34) months. Preoperatively, 12 of 15 hips (80%) were IHDI grade 4 and 3 of 15 (20%) were IHDI grade 3. Mean acetabular index was 29±8 (range, 19 to 46) degrees. Patients underwent open reduction (15 hips), adductor tenotomy (14 hips), femoral osteotomy (10 hips), and pelvic osteotomy (12 hips). At a mean follow-up of 40±16 (range, 13 to 71) months, 13 of 15 hips were IHDI grade 1 (86.7%), 1 was IHDI grade 2 (6.7%), and 1 hip was IHDI grade 3 (6.7%). The mean postoperative migration index was 7%±24% (range, −30% to 46%); the mean acetabular index was 22±8 (range, 9 to 38) degrees. No patients developed radiographically significant osteonecrosis. Complications included 2 femur fractures (13.3%) and 1 symptomatic implant that required early removal. One patient underwent further reconstructive hip surgery. CONCLUSIONS:: In this series of infants with hip dislocations and underlying spasticity, open reduction±pelvic osteotomy and/or femoral osteotomy has a nearly 90% success rate in achieving and maintaining adequate hip reduction at intermediate-term follow-up. In the unique population of infants with dislocated hips and underlying spasticity, comprehensive hip reconstruction is largely successful with an acceptable rate of complications. LEVEL OF EVIDENCE:: Level IV—retrospective. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Schnepp B.C.,The Childrens Hospital Of Philadelphia | Johnson P.R.,The Childrens Hospital Of Philadelphia
Advances in Experimental Medicine and Biology | Year: 2015

This chapter discusses the emerging field of vector-mediated antibody gene transfer as an alternative vaccine for infectious disease, with a specific focus on HIV. However, this methodology need not be confined to HIV-1; the general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets like hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis. This approach is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, via a recombinant adeno-associated virus (rAAV) vector; this in turn results in long-term endogenous antibody expression from the injected muscle that confers protective immunity. Vector-mediated antibody gene transfer can rapidly move existing, potent broadly cross-neutralizing HIV-1-specific antibodies into the clinic. The gene transfer products demonstrate a potency and breadth identical to the original product. This strategy eliminates the need for immunogen design and interaction with the adaptive immune system to generate protection, a strategy that so far has shown limited promise. © American Society of Gene and Cell Therapy 2015.

Blevins E.,The Childrens Hospital Of Philadelphia
Journal of Pediatric Hematology/Oncology | Year: 2014

We report extensive thrombotic complications of inferior vena cava (IVC) filters that were placed for primary prophylaxis in 2 pediatric trauma patients with spinal cord injuries. Although thrombosis is a known common complication in adults with IVC filters, we were unable to find any reports in the literature of this complication in children. These cases highlight a significant problem with the use of prophylactic IVC filters that are not subsequently retrieved, particularly in young trauma patients with decades to live. The overall reported complications of IVC filters in the pediatric literature are also reviewed. © 2014 by Lippincott Williams & Wilkins.

Grigoriou E.,The Childrens Hospital Of Philadelphia
Journal of Pediatric Orthopaedics | Year: 2014

BACKGROUND:: Aicardi syndrome (ACS) is a rare neurodevelopmental disorder that was classically characterized by the triad of agenesis of corpus callosum, infantile spasms, and chorioretinal lacunae. As new cases emerge and new common phenotypic features are being described in subsequent reports, new modified diagnostic criteria have been proposed that now classify the observed costovertebral abnormalities as supporting diagnostic features. To our knowledge there are no previous studies focusing and describing the scoliosis observed in children with ACS.METHODS:: We screened billing lists to identify patients seen in the Division of Orthopaedic Surgery at our institution with a diagnosis of ACS that were treated for scoliosis after 2001. A total of 5 patients were identified. Medical records and radiographs were retrospectively reviewed in all cases. In all of the patients the diagnosis of ACS had been confirmed through complete genetic evaluation and advanced imaging.RESULTS:: The mean age when scoliosis was first noticed was 3.9±4.2 years (range, 0.5 to 10.5 y) with a mean Cobb angle of 22.5±6.7 degrees (range, 10 to 27 degrees). The mean age at the first orthopedic visit was 5.8±5.0 years (range, 1.5 to 13 y) with a progressed mean Cobb angle of 39.5±17.3 degrees (range, 15 to 57 degrees). Congenital vertebral anomalies were observed in 1 patient. Three patients were treated surgically; 1 of the 3 patients had a surgical complication with loss of intraoperative neuromonitoring signals. Two patients had not undergone surgery at the last visit with a mean Cobb angle of 75.5 degrees. The mean postoperative follow-up for the surgical group (cases 1 to 3) was 3±3.6 years (range, 0.6 to 7.2 y) and the mean total follow-up for both groups was 6.6±2.5 years (range, 2.6 to 8.6 y).CONCLUSIONS:: Scoliosis in ACS can represent a clinically significant problem that is underdiagnosed and overshadowed by the other severe medical complications associated with the syndrome. Our data suggest that scoliosis in patients with ACS is rapidly progressive and bracing is ineffective; early screening, close observation, and low threshold for referral to an orthopedic surgeon are crucial.LEVEL OF EVIDENCE:: Level IV—case series. © 2014 by Lippincott Williams & Wilkins

Yellin J.L.,The Childrens Hospital Of Philadelphia
Journal of Pediatric Orthopaedics | Year: 2015

BACKGROUND:: Osteochondritis dissecans (OCD) is a condition that oftentimes causes significant knee pain in pediatric patient populations. If left untreated, OCD significantly increases the risk of developing degenerative osteoarthritis along with its associated consequences and costs. Although a genetic component has been suggested to play a role in this disorder, few studies have been carried out in order to determine the underlying genetic etiology of this relatively common complex trait. The goal of our study was to perform an initial genome-wide association study (GWAS) to uncover candidate loci associated with the pathogenesis of OCD. METHODS:: Blood samples were acquired from 2 cohorts, aged 0 to 18 years old, consisting of 209 OCD cases and 1855 population-matched controls. Agencourt Genfind DNA isolation technology was used to isolate high-quality DNA from each sample. Genotype data was then generated utilizing the Illumina Infinium BeadChip array to examine single-nucleotide polymorphisms (SNPs). RESULTS:: In an initial GWAS analysis of our cohort, where a SNP was excluded if the Hardy-Weinberg Equilibrium test P<0.0001, the minor allele frequency<5%, and the genotyping call rate<90%, we obtained our first results for OCD. Although there was no SNP strictly reaching the threshold for genome-wide significance at this early stage, multiple SNPs (35) at several loci revealed evidence of suggestive association with OCD (P<5.0×10). CONCLUSIONS:: The results from our preliminary study are encouraging. Herein we not only discuss the relevance and applicability of GWAS in studying a genetic basis for OCD, but have also identified top signals that may suggest loci involved in coordinated expression as well as a transcription factor involved in development that may be highly relevant to this trait. CLINICAL RELEVANCE:: If genetic predispositions for OCD are detected early enough in life, attempts at activity modification, counseling, and orthopaedic monitoring may successfully reduce progression of this condition, which may lead to progressive osteoarthritis in the third to fourth decade in at-risk patients. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Phillips M.C.,The Childrens Hospital Of Philadelphia
Sub-Cellular Biochemistry | Year: 2010

High density lipoprotein (HDL) possesses important anti-atherogenic properties and this review addresses the molecular mechanisms underlying these functions. The structures and cholesterol transport abilities of HDL particles are determined by the properties of their exchangeable apolipoprotein (apo) components. ApoA-I and apoE, which are the best characterized in structural terms, contain a series of amphipathic a-helical repeats. The helices located in the amino-terminal two-thirds of the molecule adopt a helix bundle structure while the carboxy-terminal segment forms a separately folded, relatively disorganized, domain. The latter domain initiates lipid binding and this interaction induces changes in conformation; the a-helix content increases and the amino-terminal helix bundle can open subsequently. These conformational changes alter the abilities of apoA-I and apoE to function as ligands for their receptors. The apoA-I and apoE molecules possess detergent-like properties and they can solubilize vesicular phospholipid to create discoidal HDL particles with hydrodynamic diameters of ~10 nm. In the case of apoA-I, such a particle is stabilized by two protein molecules arranged in an anti-parallel, double-belt, conformation around the edge of the disc. The abilities of apoA-I and apoE to solubilize phospholipid and stabilize HDL particles enable these proteins to be partners with ABCA1 in mediating efflux of cellular phospholipid and cholesterol, and the biogenesis of HDL particles. ApoA-I-containing nascent HDL particles play a critical role in cholesterol transport in the circulation whereas apoE-containing HDL particles mediate cholesterol transport in the brain. The mechanisms by which HDL particles are remodeled by lipases and lipid transfer proteins, and interact with SR-BI to deliver cholesterol to cells, are reviewed. © Springer Science+Business Media B.V. 2010.

The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ2 or Fisher’s exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.Bone Marrow Transplantation advance online publication, 9 May 2016; doi:10.1038/bmt.2016.84. © 2016 Macmillan Publishers Limited

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