Medicine and Health Sciences Commons^™

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Prechemotherapy And Intravenous Chemotherapy Eras., Evan B. Selzer, R. Joel Welch, Pascal Jabbour, Ann M. Leahey, Carol L. Shields

Wills Eye Hospital Papers

Purpose: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB) however, little information exists regarding its use in older patients (>5 years). In the present study, we evaluate the use of IAC (2008-2018) for RB in older patients and compare the outcomes to those in the prechemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Methods: A retrospective analysis of all patients older than 5 years treated with IAC for RB from 2008-2018. Comparisons were made to 26 active RB cases in older children treated in the prechemotherapy era and to 12 active RB cases treated in the IVC era.

Results: There were …

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in …

Effects Of The 2017 Clinical Practice Guidelines On Hypertension In Children And Adolescents: A Commentary, Bonita Falkner

Department of Medicine Faculty Papers

No abstract provided.

Biochemical And Clinical Response After Umbilical Cord Blood Transplant In A Boy With Early Childhood-Onset Beta-Mannosidosis., Troy C. Lund, Weston P. Miller, Julie B. Eisengart, Katrina Simmons, Laura Pollard, Deborah L. Renaud, David A. Wenger, Marc C. Patterson, Paul J. Orchard

Department of Neurology Faculty Papers

BACKGROUND: Deficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available.

METHODS: We report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease.

RESULTS: We show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of …

Promoting Adherence To Influenza Vaccination Recommendations In Pediatric Practice., Lloyd N. Werk, Maria Carmen Diaz, Adriana Cadilla, James P. Franciosi, Jobayer Hossain

Aria Health Papers

OBJECTIVES: In the United States, nonadherence to seasonal influenza vaccination guidelines for children and adolescents is common and results in unnecessary morbidity and mortality. We conducted a quality improvement project to improve vaccination rates and test effects of 2 interventions on vaccination guidelines adherence.

METHODS: We conducted a cluster randomized control trial with 11 primary care practices (PRACTICE) that provided care for 11 293 individual children and adolescents in a children's health care system from September 2015 through April 2016. Practice sites (with their clinicians) were randomly assigned to 4 arms (no intervention [Control], computerized clinical decision support system [CCDSS], …

Biomarkers In Patients With Mucopolysaccharidosis Type Ii And Iv., Honoka Fujitsuka, Kazuki Sawamoto, Hira Peracha, Robert W. Mason, William Mackenzie, Hironori Kobayashi, Seiji Yamaguchi, Yasuyuki Suzuki, Kenji Orii, Tadao Orii, Toshiyuki Fukao, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Glycosaminoglycans (GAGs), dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS), are the primary biomarkers in patients with mucopolysaccharidoses (MPS); however, little is known about other biomarkers. To explore potential biomarkers and their correlation with GAGs, blood samples were collected from 46 MPS II patients, 34 MPS IVA patients, and 5 MPS IVB patients. We evaluated the levels of 8 pro-inflammatory factors (EGF, IL-1β, IL-6, MIP-1α, TNF-α, MMP-1, MMP-2, and MMP-9), collagen type II, and DS, HS (HS0S, HSNS), and KS (mono-sulfated, di-sulfated) in blood. Eight biomarkers measured were significantly elevated in untreated MPS II patients, compared with those …

Whole Genome Metagenomic Analysis Of The Gut Microbiome Of Differently Fed Infants Identifies Differences In Microbial Composition And Functional Genes, Including An Absent Crispr/Cas9 Gene In The Formula-Fed Cohort, Matthew D. Di Guglielmo, Karl Franke, Courtney Cox, Erin L. Crowgey

Department of Pediatrics Faculty Papers

Background: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short- term or long-term composition and function of the gut microbiome.

Results: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence …

Quantitative Sensory Testing In Children With Sickle Cell Disease: Additional Insights And Future Possibilities., Robin E. Miller, Dawn S. Brown, Scott W. Keith, Sarah E. Hegarty, Yamaja Setty, Claudia M. Campbell, Suzanne M. Mccahan, Suhita Gayen-Betal, Hal Byck, Marie Stuart

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Quantitative sensory testing (QST) is used in a variety of pain disorders to characterize pain and predict prognosis and response to specific therapies. In this study, we aimed to confirm results in the literature documenting altered QST thresholds in sickle cell disease (SCD) and assess the test-retest reliability of results over time. Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat and cold detection and pain threshold testing using a Medoc TSAII. Participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months. An important facet of our study was the development and …

Health Insurance Coverage Of Recommended Gender-Affirming Health Care Services For Transgender Youth: Shopping Online For Coverage Information, Nadia L. Dowshen, Julie Christensen, Siobhan Gruschow

Student Papers, Posters & Projects

We assessed online health insurance plan indication of coverage and accessibility of information for recommended services for transgender youth (TY). Content analysis was performed for plans used at a pediatric Gender Clinic by reviewing information about coverage of puberty blockers, hormones, masculinizing chest surgery, and counseling. Transgender-specific exclusions and the time required for the research assistant to review each plan's online information were noted. No plan (0%; n=36) indicated coverage of all four categories of recommended services online. Forty-nine percent indicated ≥1 transgender-specific exclusion. The median time required for a research assistant to review online coverage information for each insurance …

Histological Chorioamnionitis Induces Differential Gene Expression In Human Cord Blood Mononuclear Leukocytes From Term Neonates., Suhita Gayen Nee’ Betal, Swati Murthy, Michael Favara, Gina Fong, Joanna Chan, Sankar Addya, Thomas H. Shaffer, Jay S. Greenspan, Vineet Bhandari, Irfan Rahman, Zubair H. Aghai

Department of Pediatrics Faculty Papers

Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. HCA is associated with increased mortality and morbidity in both premature and term neonates. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. The objective of this study was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates to identify key genes and pathways involved in HCA. We found 366 differentially expressed probe IDs with exposure to HCA …

Maternal And Gestational Influences On Childhood Blood Pressure., Bonita Falkner

Department of Medicine Faculty Papers

Exposures that contribute to a sub-optimal intrauterine environment can have an effect on the developing fetus. Impaired fetal growth that results in low birth weight is an established risk factor for cardio-metabolic disorders later in life. Recent epidemiologic and prospective cohort studies that include the maternal and gestational period have identified maternal and gestational conditions that confer increased risk for subsequent cardio-metabolic disorders in the absence of low birth weight. Maternal pre-conception health status, including chronic obesity and type 2 diabetes, increase risk for childhood obesity and obesity-related higher blood pressure (BP) in child offspring. Maternal gestational exposures, including gestational …

A Closer Look At Arsa Activity In A Patient With Metachromatic Leukodystrophy., Kathleen Doherty, S. Barron Frazier, Matthew Clark, Anna Childers, Sumit Pruthi, David A. Wenger, Jessica Duis

Department of Neurology Faculty Papers

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Pharmacological And Non-Pharmacological Treatments For The Neonatal Abstinence Syndrome (Nas)., A. K. Mangat, G. M. Schmölzer, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of …

Minimally Invasive Surgery In Neonates With Congenital Anomalies: Experience From The Nsqip-P, Emily Sagalow, Katerina Dukleska, Md, Courtney Devin, Md, Erin Teeple, Md, Scott W. Cowan, Md, Charles D. Vincour, Md, Loren Berman, Md

Phase 1

Background: Congenital diaphragmatic hernias (CDH) and tracheoesophageal fistulas (TEF) are managed with minimally invasive surgery (MIS) or open surgery. Little is known about the patient populations and outcomes for those treated by each approach. Hypothesis/Specific Aims: We expect that there will be fewer complications, better outcomes, and longer operative times for the MIS group versus the open group.

Methods: National Surgical Quality Improvement Program-Pediatric Participant Use Files (NSQIP-P PUFs) from 2012-2015 were used to identify neonates (up to 30 days old) who underwent CDH and TEF repair. The patient characteristics, post-operative complications, and 30-day mortality were analyzed using multivariable logistic …

Management Of Retinoblastoma In Older Children (>5 Years) Using Intra-Arterial Chemotherapy: Comparison Of Outcomes To Pre-Chemotherapy And Intravenous Chemotherapy Eras, Evan Selzer, Ms, R. Joel Welch, Md, Pascal Jabbour, Md, Ann Leahey, Md, Carol L. Shields, Md

Phase 1

Introduction: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB), but little information exists regarding its use in older patients (>5 years). We evaluate the use of IAC (2008-2018) for RB in older patients and compare outcomes to those in the pre-chemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras.

Objective: To evaluate the hypothesis that IAC is effective in managing RB in older patients.

Methods: We performed a retrospective analysis of all patients older than 5 years who were treated with IAC for RB from 2008-2018 on the Ocular Oncology Service at the Wills Eye Hospital. Comparisons were made to historic, …

Cross-Sectional Analysis Of Sound Levels In The Neonatal Intensive Care Unit (Nicu) At Thomas Jefferson University Hospital, Caroline Komlo, Martin Morris, Robert Ries, Michael Velez

Phase 1

Introduction . Infants in the NICU are considered at greater risk of developmental delay. It is now known that excessively loud noise can have a negative impact on parameters such as blood pressure, breathing, heart beat and oxygen saturation. Previous research has concluded that the optimal decibel (dB) level for proper growth of neonate hair cells rests around 45dB. Consequently, the American Academy of Pediatrics recommends that noise levels in the NICU be maintained to a maximum of 45dBA. However, little research has focused on designing new noise-altering products and their impact on neonatal outcomes.

Methods. This was a cross …