Globoid-cell leukodystrophy (GLD) is an inherited demyelinating disease caused by the deficiency of the lysosomal enzyme galactosylceramidase (GALC). A previous study in the murine model of GLD (twitcher) demonstrated a dramatic synergy between CNS-directed adeno-associated virus 2/5 (AAV2/5) gene therapy and myeloreductive bone marrow transplantation (BMT). However, the mechanism by which these two disparate therapeutic approaches synergize is not clear. In addition, the therapeutic efficacy may have been limited since the CNS-directed gene therapy was restricted to the forebrain and thalamus. In the current study, intrathecal and intracerebellar injections were added to the therapeutic regimen and the mechanism of synergy between BMT and gene therapy was determined. Although AAV2/5 alone provided supraphysiological levels of GALC activity and reduced psychosine levels in both the brain and spinal cord, it significantly increased CNS inflammation. Bone marrow transplantation alone provided essentially no GALC activity to the CNS and did not reduce psychosine levels. When AAV2/5 is combined with BMT, there are sustained improvements in motor function and the median life span is increased to 123 d (range, 92–282 d) compared with 41 d in the untreated twitcher mice. Interestingly, addition of BMT virtually eliminates both the disease and AAV2/5-associated inflammatory response. These data suggest that the efficacy of AAV2/5-mediated gene therapy is limited by the associated inflammatory response and BMT synergizes with AAV2/5 by modulating inflammation.
Purpose
Adrenocortical carcinoma (ACC) is a rare tumor in children with important distinctions from the adult disease. We reviewed the National Cancer Data Base (NCDB) to determine factors associated with long-term survival.
Methods
The NCDB was queried for patients less than 18 years of age who were diagnosed with ACC between 1998 and 2011. Kaplan–Meier analysis was utilized to determine factors significantly associated with overall survival.
Results
A total of 111 patients were included (median age: 4 years, 69% female). ACC was more common in the youngest cohort, with 48% of cases occurring in children younger than the age of 3. Median tumor size was 9.5 cm (IQR: 6.5–13.0), and 87% of patients underwent some form of surgical resection. Among children with available data, 19 of 62 presented with metastases. Overall 1- and 3-year survival was 70% and 64%, respectively. Age, tumor size, extension of tumor into surrounding tissue, and metastatic disease were all found to be significantly associated with survival. Among patients who underwent a surgical procedure, margin status was also found to be significantly associated with survival.
Conclusion
Age, tumor size, extension of tumor, metastatic disease, and margin status are significantly associated with long-term survival in children with adrenocortical carcinoma.
Purpose
Since trauma is the leading cause of death and disability among children, understanding injury patterns may reduce morbidity and mortality through targeted prevention efforts. The purpose of this study was to identify pediatric injury patterns by year of age using a large national database.
Methods
We searched the National Trauma Database (NTDB) Research Data Set 7.0 for patients aged 0–18 years with the following relevant ICD-9 external-cause-of-injury codes (e-codes). We also reviewed our institutional trauma registry data (1999–2009). Data were analyzed using χ2 analysis and ANOVA with significance defined as p < 0.05.
Results
We identified 354,196 pediatric trauma patients. The leading MOI were motor-vehicle collisions (MVC) for ages 10–18 years and falls for ages 0–9 years. Fire was the second leading MOI among 1-year-olds, but not a major MOI in other age groups. Penetrating trauma was the MOI for 21% of injuries among adolescents with public or no insurance (versus 7.5% adolescents with private insurance). Injury severity scores were highest for children < 1 year old and children 14–18 years old. Our review of 1209 patients from our institution yielded additional detail.
Conclusion
MVC and falls remain leading pediatric MOI. In our year-of-age analysis, we found several interesting trends, including a higher-than-expected rate of penetrating trauma. Our findings may support targeted injury prevention efforts.
Our study demonstrates that non-Hispanic Black and Hispanic infants are significantly more likely to be diagnosed with NEC. In addition, non-Hispanic Black and Hispanic infants have higher odds of death after NEC compared to non-Hispanic White infants. Further studies are necessary to investigate the etiology of these health disparities and to test interventions to improve these health outcomes.
Background
Thrombosis in the neonatal population is rare, but increasing. Its incidence and management are not well understood.
Objectives
To investigate the incidence, associated factors, and management of thrombosis in the neonatal intensive care unit (NICU) population.
Patients/Methods
We performed a retrospective cohort study of infants admitted to a Pediatrix Medical Group‐affiliated NICU from 1997 through 2015. We determined the prevalence of venous and arterial thrombosis, and assessed demographic characteristics and known risk factors. Categorical variables were compared with the Pearson χ2 test and continuous variables with Wilcoxon rank‐sum tests. Stepwise logistic regression was used to identify associated factors. The primary outcome was incidence of thrombosis. Secondary analyses investigated correlations between clinical and demographic characteristics and thrombosis.
Results
Among 1 158 755 infants, we identified 2367 (0.20%) diagnosed with thrombosis. In a multivariable regression analysis, prematurity, male sex, congenital heart disease, sepsis, ventilator support, vasopressor receipt, central venous catheter, invasive procedures, and receipt of erythropoietin were associated with increased risk of thrombosis, while Black race and Hispanic ethnicity were associated with reduced risk. The majority of infants diagnosed with thrombosis (73%) received no anticoagulation, but anticoagulant use in infants with thrombosis was higher than those without (27% versus 0.2%, P < .001). Thrombosis in infants was associated with higher mortality (11% versus 2%, P < .001) and longer hospital stays (57 days, [interquartile range (IQR) 28‐‐100] versus 10 days, [IQR 6‐‐22], P < .001).
Conclusions
In the largest national study to date, we found that thrombosis in NICU patients is associated with prematurity, low birth weight, sepsis, and invasive procedures.
Purpose
Variable approaches to the care of infants with congenital diaphragmatic hernia (CDH) by multiple providers may contribute to inconsistent care. Our institution developed a comprehensive evidence-based protocol to standardize the management of CDH infants. This report reviews patient outcomes prior to and after implementation of the protocol.
Methods
Retrospective chart review of CDH infants managed with individualized care (Pre-protocol group, January 1997–December 2001, n=22) or on the protocol (Protocol group, January 2002–July 2009, n=47). Survival and other categorical variables were compared by chi square analysis and continuous variables were compared using one-sided ANOVA analysis with significance defined as p<0.05.
Results
Survival to discharge was significantly greater in the Protocol group (40/47 (85%)) than the Pre-protocol group (12/22 (52%) p=.006) although mean gestational age, mean birth weight, and expected survival were not statistically different between the two groups. The use of supportive therapies, including high frequency jet ventilation, inhaled nitric oxide, and extracorporeal life support was similar between groups as well.
Conclusions
Since implementation of a management protocol for infants with CDH, survival has improved significantly compared with expected survival and pre-protocol controls. Reduction in the variability of care through use of an evidence-based protocol use may improve the survival of CDH infants.
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