High expression of Toll-like receptor 7 is a survival factor in pediatric medulloblastoma.

PURPOSE: Medulloblastoma is an embryonal brain tumor that predominantly occurs in childhood with a wide histological and molecular variability. Our aim was to investigate the expression of Toll-like receptors (TLRs), their association with the infiltration of immune cells and with the histological subgroups, and, also, with the overall survival of patients. METHODS: Fifty-six paraffin-preserved biopsies from children with medulloblastoma of the classic, desmoplastic, and anaplastic subtypes were included. Microarrays of tissues were performed, and the infiltration of T and NK cells was quantified, as well as the expression of TLR7, TLR8, and TLR9. For all statistical analyses, significance was p < 0.05. RESULTS: CD4 + and CD8 + T lymphocytes and NK cells were found infiltrating the tumor. The infiltration of NK and CD4 + cells was greater in the classic and desmoplastic subtypes than in anaplastic. We found an important expression of TLRs in all medulloblastomas, but TLR7 and TLR8 were considerably higher in classic and desmoplastic subtypes than in anaplastic. Importantly, we observed that TLR7 was a prognostic factor for survival. CONCLUSIONS: Medulloblastomas present cellular infiltration and a differential expression of TLRs depending on the histological subtype. TLR7 is a prognostic factor of survival that is dependent on treatment and age.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates / Heterogeneidad internacional en las tasas de mortalidad pediátrica por COVID-19

Abstract Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Resumen Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.