Jorge Humberto Tapia-Pérez

The role of statins in neurosurgery

Statins are drugs used to control cholesterol disorders and prevent cardiovascular diseases. Their denominated pleiotropic effects have demonstrated a broad action spectrum that might profit some neurological and neurosurgical diseases. These effects are correlated to dose and kind of statin. We accomplished a systematic review in PubMed and MEDLINE about studies of statins and main neurosurgical diseases. If statins are administered after subarachnoid hemorrhage, a significant lower incidence of vasospasm as well as delayed ischemic deficits and decreased mortality could be found; the results of a large multicenter trial are expected. In other complex diseases as intracerebral hemorrhage or traumatic brain injury, the evidence for positive effects of a treatment with statin increased. Additionally, promising experimental results indicate that high statin doses are able to promote cell death in tumor cells, especially in gliomas. Moreover, experimental and observational studies suggest the ability of statins to modulate the immune system, by that they can reduce incidence and severity of sepsis. The origin of these multiple effects from neuroprotection to tumoral apoptosis is not totally explained so far. Recent data in literature are discussed in this review. More trials in humans are urgently required to finally determine if statins could contribute to the current management of neurosurgical diseases.

Effect of increased glucose levels on short-term outcome in hypertensive spontaneous intracerebral hemorrhage

OBJECTIVE Spontaneous intracerebral hemorrhage (ICH) can be a devastating event. Increased glucose levels in the plasma may be related to poor outcomes; however, the precise association remains unclear. METHODS We retrospectively assessed 116 patients with hypertensive ICH. Glucose level in the plasma was assessed at days 0, 1, and 3. Outcome variables were mortality within 7 and 30days and the National Institutes of Health Stroke Scale (NIHSS) score at day 14 after ICH onset. RESULTS Twenty deaths had occurred by day 7, and the 30-day mortality rate was 31.9%. Hyperglycemia at day 0 was significantly more common in patients who died within 7days or 30days. Hyperglycemia at day 1 was more common in patients with an NIHSS score >15 on admission and at day 14. No differences in glucose levels were found between diabetic and non-diabetic patients. Among non-diabetic patients, higher glucose levels were related to poorer outcomes (death or an NIHSS score >15). In multivariate analysis, glucose levels >140mg/dL at day 1 were related to the 30-day mortality (hazard ratio=2.65; 95% confidence interval [CI]=1.15-6.12, p=0.02), and glucose levels >160mg/dL at day 1 were associated with an NIHSS score >15 at day 14 (odds ratio=3.08; 95% CI=0.9-10.5, p=0.07). White blood cell counts were directly associated with poorer outcomes and significantly correlated to glucose levels. CONCLUSION Initially increased glucose levels and increased levels within 24h of ICH onset were related to poorer outcomes. Altered glucose metabolism may be due to inflammatory cell activation. Further studies are needed to clarify the association between immune activation and glucose metabolism after ICH onset.

Assessment of systemic cellular inflammatory response after spontaneous intracerebral hemorrhage.

OBJECTIVE After spontaneous intracerebral hemorrhage (ICH) a local and systemic inflammatory response is activated. Interleukin-6 (IL) is one of most relevant orchestrators of inflammatory responses in the brain and is released from multiple immune cells, including neutrophils. Herby we assessed the relevance of systemic inflammation in patients suffering ICH. METHODS From October 2010 to October 2011 we included in our routine of laboratory investigations besides to C-reactive protein (CRP), the addition of IL-6 and an analysis of the subpopulation of circulating blood cells. Values at admission, at 3rd and 7th day after admission were evaluated. We analyzed 43 patients with non-traumatic ICH; stroke-related ICH or tumor associated hemorrhage were excluded. Outcome variables were 30 and 90-day mortality and NIHSS at discharge. A natural logarithmic transformation of IL-6, lymphocytes, and monocytes was used. RESULTS 8.6% died within 30-days and mortality increased to 39.5% at 90th day. Total leukocytes and neutrophils as well as IL-6 at admission were statistically significant increased among patients who died within 30days after ICH onset (p=0.002). IL-6 and CRP in follow-up (3rd and 7th day) were higher among patients with poor outcome (NIHSS >15). The number of circulating lymphocytes and monocytes was not different in measurement. Leukocytes and neutrophils at 3rd day after admission were augmented in patients with respiratory infection and CRP in follow-up increased if some kind of infection was clinically or microbiologically detected. IL-6 at admission and in follow-up and monocytes at 7th day were related to ICH volume. CRP-values at 3rd or 7th day but not at admission were associated to bigger ICH-volume. The values of IL-6 were highly correlated to 30-day mortality and volume of ICH as CRP only with ICH volume. CONCLUSION After ICH onset a systemic activation of immune system seems to be induced and may be influencing outcome. Peripheral recruitment of leukocytes, especially neutrophils could be a target for future therapeutic interventions. Because of the tighter correlation of IL-6 at admission, it might be more accurate for prognostic issues than CRP.

Resveratrol decreases B-cell lymphoma-2 expression and viability in GH3 pituitary adenoma cells of the rat

Objective Resveratrol is a phytoestrogen with various antiproliferative and proapoptotic effects. This in vitro study aimed to analyze the effect of resveratrol on the viability and expression of modulators of apoptosis in GH3 pituitary adenoma cells of the rat. Methods GH3 cells were incubated with resveratrol concentrations from 20 to 100 μM for 48–72 hours. Cell viability was quantified using a hemocytometer. We assessed the ability of resveratrol to kill GH3 cells by an enzyme-linked immunosorbent assay (ELISA) of nucleosome liberation and by DNA degradation (unidimensional gel electrophoresis). Relative messenger RNA (mRNA) expression of survivin, B-cell lymphoma-2 protein (BCL-2) and BCL-2-associated X protein (BAX) normalized to β2 microglobulin was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Results GH3 cell survival significantly decreased with increasing concentrations of resveratrol. In GH3 cells treated with 100 μM resveratrol, ELISA demonstrated a significant rise of nucleosome liberation, which typically occurs during apoptosis. In parallel, gel electrophoresis showed degradation of DNA into random fragments, pointing to a necrotic mode of cell death in most GH3 cells. In GH3 cells treated with 100 μM resveratrol, qRT-PCR detected a significant decrease of BCL-2 mRNA expression and a decrease of survivin mRNA expression, whereas a change of BAX mRNA expression could not be found. The BAX/BCL-2 ratio was significantly increased in GH3 cells after resveratrol treatment. Conclusions Resveratrol reduces GH3 cell viability in a dose-dependent manner by inducing nonapoptotic cell death and apoptosis. Apoptosis in GH3 cells is probably mediated by resveratrol-dependent downregulation of apoptosis inhibitors, namely BCL-2 and possibly survivin. Further investigation of the potential effects of resveratrol on pituitary adenoma cells is warranted.

Experience with a new design of endoretractor for gasless laparoscopic cholecystectomy.

Background Cholecystectomy has replaced open surgery and is regarded as the standard procedure today. The pneumoperitoneum needed to create working space can induce cardiovascular changes. Gasless laparoscopic surgery is effective; we evaluate a new retractor design. Methods Patients older than 15 years with elective cholecystectomy and American Society of Anesthesiology I-II were consequently assigned to conventional or gasless surgery. We evaluated surgical time, hemodynamic stability, hours of hospital stay, and days of recuperation. Results We analyzed 22 cholecystectomies, 10 by the gasless technique and 12 by gas laparoscopy. We did not observe significant differences in surgical time, length of hospital stay, or days of recuperation. However, surgical exposition time was longer in the retractor group than was expected by chance (P<0.05). Hemodynamic stability was similar between the groups. Conclusions Similar surgical and recuperation times and length of hospital stay were observed. Our design is comparable with conventional laparoscopic surgery despite longer surgical exposition time.

Survival in granular cell astrocytomas.

BACKGROUND Granular cell astrocytomas (GCAs) are rarely encountered aggressive glial neoplasms. Treatment options comprise surgery, radiotherapy, and chemotherapy. Due to the small number of cases, a standard therapeutic regimen for GCA does not exist. MATERIAL AND METHODS We report on the case of a 64-year-old woman with GCA subjected to tumor biopsy followed by radiochemotherapy with temozolomide. We provide clinical, histopathologic, and magnetic resonance imaging findings as well as a complete follow-up. To assess the relation of age, gender, time of publication, and different treatment options with survival we performed log-rank tests and calculated Cox regression models and hazard ratios in data from all available reports on GCA. RESULTS A significant difference in survival rates in favor of adjuvant therapy (radiotherapy or radiochemotherapy) at 12 months was found. Age > 70 years at the time of diagnosis had a significantly unfavorable impact on survival at 12 months. Although not statistically significant, a tendency toward higher probability of survival at 12 months was found in cases reported after 2002. In surgically treated patients, we could not find a significant impact of extent of resection on survival. A significant impact of gender on survival was not found. CONCLUSION Adjuvant therapy is significantly related to a higher probability of survival at 12 months and may therefore be recommended for patients with a GCA. Further analysis of these rare neoplasms is warranted.