III.

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Purpose: The purpose of this study was to determine whether seeding density of placental mesenchymal stromal cells (PMSCs) on extracellular matrix (ECM) during in utero repair of myelomeningocele (MMC) affects motor function and neuronal preservation in the ovine model. Methods: MMC defects were surgically created in 33 fetuses and repaired following randomization into four treatment groups: ECM only (n=10), PMSC-ECM (42K cells/cm2) (n=8), PMSC-ECM (167K cells/cm2) (n=7), or PMSC-ECM (250–300K cells/cm2) (n=8). Motor function was evaluated using the Sheep Locomotor Rating Scale (SLR). Serial sections of the lumbar spinal cord were analyzed by measuring their cross-sectional area which were then normalized to normal lambs. Large neurons (LN, diameter 30–70μm) were counted manually and density calculated per mm2 gray matter. Results: Lambs treated with PMSCs at any density had a higher median SLR score (15 [IQR 13.5–15]) than ECM alone (6.5 [IQR 4–12.75], p=0.036). Cross-sectional areas of spinal cord and gray matter were highest in the PMSC-ECM (167K/cm2) group (p=0.002 and 0.006, respectively). LN density was highest in the greatest density PMSC-ECM (250–300K/cm2) group (p=0.045) which positively correlated with SLR score (r=0.807, p<0.0001). Conclusions: Fetal repair of myelomeningocele with high density PMSC-ECM resulted in increased large neuron density, which strongly correlated with improved motor function.

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BACKGROUND Trauma is the leading cause of death in children, and most deaths occur within 24 hours of injury. A better understanding of the causes of death in the immediate period of hospital care is needed. METHODS Trauma admissions younger than 18 years from 2009 to 2019 at a Level I pediatric trauma center were reviewed for deaths (n = 7,145). Patients were stratified into ages 0–6, 7–12, and 13–17 years old. The primary outcome was cause of death, with early death defined as less than 24 hours after trauma center arrival. RESULTS There were 134 (2%) deaths with a median age of 7 years. The median time from arrival to death was 14.4 hours (interquartile range, 0.5–87.8 hours). Half (54%) occurred within 24 hours. However, most patients who survived initial resuscitation in the emergency department died longer than 24 hours after arrival (69%). Traumatic brain injury was the most common cause of death (66%), followed by anoxia (9.7%) and hemorrhage (8%). Deaths from hemorrhage were most often in patients sustaining gunshot wounds (73% vs. 11% of all other deaths, p < 0.0001), more likely to occur early (100% vs. 50% of all other deaths, p = 0.0009), and all died within 6 hours of arrival. Death from hemorrhage was more common in adolescents (21.4% of children aged 13–17 vs. 6.3% of children aged 0–6, and 0% of children aged 7–12 p = 0.03). The highest case fatality rates were seen in hangings (38.5%) and gunshot wounds (9.6%). CONCLUSION Half of pediatric trauma deaths occurred within 24 hours. Death from hemorrhage was rare, but all occurred within 6 hours of arrival. This is a critical time for interventions for bleeding control to prevent death from hemorrhage in children. Analysis of these deaths can focus efforts on the urgent need for development of new hemorrhage control adjuncts in children. LEVEL OF EVIDENCE Epidemiological study, level IV.