RESUMO
AIM: The aim of the study was to investigate the role of umbilical cord blood lactate as early predictors of hypoxic ischemic encephalopathy in newborns with perinatal asphyxia and to evaluate their sensitivity and specificity for the early identification of hypoxic ischemic encephalopathy infants. METHODS: We performed a descriptive cross sectional study between April 2014 and April 2015 at Hue Central Hospital, Vietnam. 41 asphyxia newborns (Apgar score ≤ 7) were included in the study. Umbilical cord blood is sampled for lactate analysis. RESULTS: Umbilical cord blood lactate levels were significantly higher among infants born with HIE (mean 8.72 ± 1.75, range 5.12 - 11.96) compared to that with asphyxic infants without HIE (mean 6.86 ± 1.33, range 4.74 - 10.30), p = 0.00. With the optimal cutoff point for umbilical cord blood lactate level of 8.12 mmol/l to susspected of HIE (area under the curve 0.799) had a sensitivity 73.7% (95% CI 48.8-90.9), specificity 86.4% (95% CI 65.1-97.1). CONCLUSION: Umbilical cord blood lactate could be used as early predictors in diagnosis of hypoxic ischemic encephalopathy in newborns with asphyxia.
RESUMO
Activation of the MAPK signaling pathway has been shown to be a unifying molecular feature in pilocytic astrocytoma (PA). Genetically, tandem duplications at chromosome 7q34 resulting in KIAA1549-BRAF fusion genes constitute the most common mechanism identified to date. To elucidate alternative mechanisms of aberrant MAPK activation in PA, we screened 125 primary tumors for RAF fusion genes and mutations in KRAS, NRAS, HRAS, PTPN11, BRAF and RAF1. Using microarray-based comparative genomic hybridization (aCGH), we identified in three cases an interstitial deletion of ~2.5 Mb as a novel recurrent mechanism forming BRAF gene fusions with FAM131B, a currently uncharacterized gene on chromosome 7q34. This deletion removes the BRAF N-terminal inhibitory domains, giving a constitutively active BRAF kinase. Functional characterization of the novel FAM131B-BRAF fusion demonstrated constitutive MEK phosphorylation potential and transforming activity in vitro. In addition, our study confirmed previously reported BRAF and RAF1 fusion variants in 72% (90/125) of PA. Mutations in BRAF (8/125), KRAS (2/125) and NF1 (4/125) and the rare RAF1 gene fusions (2/125) were mutually exclusive with BRAF rearrangements, with the exception of two cases in our series that concomitantly harbored more than one hit in the MAPK pathway. In summary, our findings further underline the fundamental role of RAF kinase fusion products as a tumor-specific marker and an ideally suited drug target for PA.
