No abstract

Anthracycline induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane prior to anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages 0 to 21 years) who received or did not receive dexrazoxane during the years 2008 to 2013. Forty-four patients with AML (ages 4.5 months to 21.7 years) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, p=0.41) or 2-year overall survival (OS) (69% vs. 69%, p=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (p=0.0262) and shortening fraction (p=0.0381) trended significantly higher in patients that received dexrazoxane compared to those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane prior to anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or OS relative to institutional controls and appears to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.

The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV) transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma.

OBJECTIVE: Pediatric hospitalizations are a missed opportunity for delivery of the human papilloma virus (HPV) vaccination. In this study, the authors’ aim was to increase HPV vaccination rates among adolescents cared for by the pediatric hospital medicine (PHM) service at our academic children’s hospital. METHODS: This quality improvement (QI) study included adolescents ≥13 years who were discharged from PHM. Interventions included: modification of discharge order sets to include vaccination status and provider training seminars regarding the delivery of the HPV vaccine. Follow-up materials were distributed to providers by e-mail. The primary outcome measure was adolescent HPV vaccination rates. Secondary outcome measures were adolescent meningococcal vaccination rates and accuracy of immunization status documentation. The balancing measure was length of stay (LOS). Data were collected via chart review. Statistical process control charts were used to analyze for special cause variation. RESULTS: From May 2019 through February 2020, 440 patients were included in this analysis. Throughout the study, HPV and meningococcal vaccination rates increased from a baseline median of 4.6% to 21.2% and 8.3% to 26.6%, respectively. HPV vaccination was not significantly associated with sex, HPV dose due, or admitting service. Accuracy of immunization status documentation and LOS remained unchanged. CONCLUSIONS: Using QI methodology we were successful in increasing HPV and meningococcal vaccination rates among hospitalized adolescents. Considering the relationship of these 2 vaccines is a potential topic of future work. Discerning the correct immunization status at time of admission may be a potential opportunity for improvement in future work.

Dapsone gel is a topical treatment for facial acne in adolescents and adults, and while systemic dapsone therapy is known to be associated with methemoglobinemia, once‐daily topical dapsone has been well tolerated with few side effects in large randomized controlled trials. We describe the first reported case of severe methemoglobinemia in a healthy adolescent using daily topical dapsone. Although the medication was prescribed for facial use only, the patient reported topical use over her back and chest as well. This case illustrates the potential for significant systemic dapsone absorption even with daily topical dosing and demonstrates the need for clear anticipatory guidance to prevent the potential morbidity and mortality associated with methemoglobinemia from improper topical dapsone use.