Long-term prognosis related to deep sedation in refractory status Epilepticus.

OBJECTIVE: To evaluate long-term prognosis in patients with refractory status epilepticus according to the level of sedation reached during drug-induced coma. MATERIALS AND METHODS: Longitudinal study of patients with status epilepticus who received anesthetics to induce therapeutic coma. Demographic data, clinical, and electroencephalographic characteristics were collected, as well as variables related to sedation. We considered as deep sedation the EEG burst-suppression patterns (suppression ratio > 50%). A GOSE (Glasgow Outcome Scale Extended) score of 7 or 8 was considered as good prognosis. A comparative study was carried out to identify predictors of good or poor prognosis at discharge, at 1 and 2 years of follow-up. RESULTS: We included 61 patients: 63.9% were men; mean age 53.5 ± 16.8 years (range 16-86 years), 39.3% reached deep sedation; 62.3% had > 48 h induced coma. The median hospital stay was 21 days, while 10 days in the intensive care unit (ICU). In the multiple regression analysis, an ICU length of stay ≥ 7 days was associated with poor prognosis at discharge and at long-term (P < .05), while deep sedation was associated only with poor long-term prognosis (1 and 2 years, P < .05). The Kaplan-Meier curve showed higher survival in the group that did not undergo deep sedation (P < .05). CONCLUSIONS: In refractory status epilepticus, deep sedation is associated with poor prognosis at long-term.

Ionizing radiation or mitomycin-induced micronuclei in lymphocytes of BRCA1 or BRCA2 mutation carriers.

BRCA1 and BRCA2 genes are essential in preserving the integrity of genome, and it is not unambiguously clear whether the heterozygosity status may affect BRCA1 or BRCA2 functions. This may have implications for the clinical management of BRCA1 and BRCA2 mutation carriers both in breast cancer (BC) screening modality and in cancer treatment based on DNA-damaging or DNA-repair-inhibiting drugs. We investigated whether lymphocytes carrying BRCA1 or BRCA2 mutations displayed an increased sensitivity to radiation or mitomycin C (MMC) in vitro treatments. Peripheral blood from 21 BRCA1 mutation carriers (12 with BC and 9 healthy), 24 BRCA2 carriers (13 with BC and 11 healthy), 15 familial BC patients without detected mutation in BRCA1 or BRCA2 and 16 controls without familial history of cancer (5 with BC and 11 healthy) were irradiated or treated with MMC. Chromosomal damage was measured using the cytokinesis-block micronucleus assay. We evaluated micronuclei (MN) and nucleoplasmic bridges (NPBs). The BRCA2 mutation carriers and familial BC patients without detected mutation in BRCA1 or BRCA2 showed less basal NPB than BRCA1 carriers and controls. The BRCA1 (+/-) or BRCA2 (+/-) lymphocytes did not have increased frequencies of MN or NPB after irradiation. In contrast, BRCA2 (+/-) lymphocytes presented higher levels of MN after MMC exposure than BRCA1 carriers and controls. The monoallelic BRCA1 or BRCA2 pathogenic mutations seem not to be associated with an enhanced radiosensitivity. The mutation of one BRCA2 allele conferred an increased sensitivity to MMC, presumably because of the role of this gene in the repair of MMC-induced DNA damage. This finding indicates that the MMC-induced MN analysis could be useful in identifying functional deficiencies of BRCA2 or genes related to BRCA2. Since MMC can be used as an anti-cancer drug, these data may be relevant for the management and follow-up of BRCA2 mutation carriers.