Depth of anesthesia measured by bispectral index and postoperative mortality: A meta-analysis of observational studies.

INTRODUCTION: Whether anesthesia depth affects postoperative mortality remains uncertain. MEASUREMENTS: Several databases were systematically searched to identify all articles studying the relationship between depth of anesthesia and postoperative mortality. Post hoc subgroup analyses were conducted for follow-up period (30 days vs. longer than 90 days) and type of surgery. MAIN RESULTS: The analysis included 38,722 patients from nine studies. We observed a significant relationship between low bispectral index (BIS) and mortality (pooled aHR, 1.22;95% CI, 1.08 to 1.38; P = 0.001; I2 = 85.4%). Post hoc subgroup analyses indicated low BIS to be linked with significantly elevated mortality risk in patients with ≥90 days follow-up (pooled adjusted hazard ratio [aHR], 1.09; 95% CI, 1.00-1.19; P = 0.01; I2 = 79.4%), but this association did not achieve significance in those with a 30 day follow-up duration (pooled aHR, 1.52; 95% CI, 0.97-2.38; P = 0.28; I2 = 79.0%). In addition, this link between postoperative mortality and low BIS was significant in those who had undergone cardiac surgery (pooled aHR, 1.30; 95% CI, 1.14 to 1.49; P < 0.001; I2 = 0.0%), but not in patients that had received other forms of surgery (pooled aHR, 1.06; 95% CI, 0.98 to 1.14; P = 0.14; I2 = 73.2%). CONCLUSIONS: We observed a significant relationship between deep anesthesia and long-term mortality, though this was not significant 30 days following surgery. In patients who had received cardiac surgery, deep anesthesia may increase mortality. However, this trend was not observed in patients who had undergone other forms of surgery.

Mitochondrial ferritin, a new target for inhibiting neuronal tumor cell proliferation.

Mitochondrial ferritin (FtMt) has a significant effect on the regulation of cytosolic and mitochondrial iron levels. However, because of the deficiency of iron regulatory elements (IRE) in FtMt's gene sequence, the exact function of FtMt remains unclear. In the present study, we found that FtMt dramatically inhibited SH-SY5Y cell proliferation and tumor growth in nude mice. Interestingly, excess FtMt did not adversely affect the development of drosophila. Additionally, we found that the expression of FtMt in human normal brain tissue was significantly higher than that of neuroblastoma, but not higher than that of neurospongioma. However, the expression of transferrin receptor 1 is completely opposite. We therefore hypothesized that increased expression of FtMt may negatively affect the vitality of neuronal tumor cells. Therefore, we further investigated the underlying mechanisms of FtMt's inhibitory effects on neuronal tumor cell proliferation. As expected, FtMt overexpression disturbed the iron homeostasis of tumor cells and significantly downregulated the expression of proliferating cell nuclear antigen. Moreover, FtMt affected cell cycle, causing G1/S arrest by modifying the expression of cyclinD1, cyclinE, Cdk2, Cdk4 and p21. Remarkably, FtMt strongly upregulated the expression of the tumor suppressors, p53 and N-myc downstream-regulated gene-1 (NDRG1), but dramatically decreased C-myc, N-myc and p-Rb levels. This study demonstrates for the first time a new role and mechanism for FtMt in the regulation of cell cycle. We thus propose FtMt as a new candidate target for inhibiting neuronal tumor cell proliferation. Appropriate regulation of FtMt expression may prevent tumor cell growth. Our study may provide a new strategy for neuronal cancer therapy.