Microembolic signals in subarachnoid hemorrhage

Microembolic signals (MES) detected by transcranial Doppler (TCD) have been reported in subarachnoid hemorrhage (SAH), although their origin and contribution to brain ischemia remain uncertain. We conducted a prospective study to evaluate the frequency of MES among patients with SAH and to determine their origin. Twenty-seven patients with SAH, comprising 15 aneurysmal and 12 non-aneurysmal patients, participated in the study. TCD evaluation was performed using a 2 MHz probe. Patients were studied three times per week during their in-patient stay to detect vasospasm, and then each middle cerebral artery (MCA) was monitored for 30 min using the Monolateral Multigate mode to detect MES. Using this method, MES were detected in 7 out of 15 patients (47%) with aneurysmal SAH and were not seen in non-aneurysmal patients (p = 0.007). Vasospasm occurred in 52% (14/27) of cases. However, clinical signs and symptoms of vasospasm were identified in only 18.5% (5/27). There was no significant relationship between MES and vasospasm (p = 0.224). Also, no relationship was found between MES and the location of the aneurysm (p = 0.685). Thus, in this study MES were only detected in aneurysmal SAH. However, we did not find a relationship between the location of the aneurysm and MES, or the presence of vasospasm and MES. Therefore, MES in patients with SAH may also originate from vascular pathology other than the aneurysm sac or vascular spasm.     

Dexmedetomidine as an anesthetic adjuvant for intracranial procedures: Meta-analysis of randomized controlled trials

This meta-analysis aimed to systematically collect the current evidence regarding the efficacy and safety of dexmedetomidine (DEX) as an anesthetic adjuvant for patients undergoing intracranial surgery. A systematic literature search of randomized controlled trials (RCT) was conducted to compare DEX with placebo or opioids in patients undergoing intracranial procedures. Hemodynamic data, opioid consumption, and recovery parameters were pooled. Eight RCT were included. Results showed that patients treated with DEX required less intraoperative treatment for hypertension and hypotension (risk ratio [RR] = 0.48, 95% confidence interval [CI] 0.31–0.75, p = 0.001; and RR = 0.66, 95% CI 0.43–1.01, p = 0.05, respectively) and less postoperative treatment for hypertension and tachycardia (RR = 0.37, 95% CI 0.17–0.79, p = 0.01; and RR = 0.14, 95% CI 0.03–0.59, p = 0.007, respectively) compared with placebo. Patients also had lower mean arterial pressure and heart rate when extubated (mean difference [MD] = −9.74 mmHg, 95% CI −12.35 to −7.12, p < 0.00001; and MD = −16.35 beats/minute, 95% CI −20.00 to −12.70, p < 0.00001, respectively), a lower intraoperative additional fentanyl consumption (MD = −0.78 μg/kg, 95% CI −1.51 to −0.05, p = 0.04), and lower postoperative antiemetic requests (RR = 0.51, 95% CI 0.33–0.80, p = 0.003). DEX may not increase extubation time, postoperative P_aCO₂, or the risk of perioperative bradycardia. Only a small number of RCT are available, but meta-analysis shows evidence that DEX as an anesthetic adjuvant during intracranial procedures leads to better perioperative hemodynamic control, less intraoperative opioid consumption, and fewer postoperative antiemetic requests.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

The efficacy and safety of teriflunomide based therapy in patients with relapsing multiple sclerosis: A meta-analysis of randomized controlled trials

The aim of this study was to evaluate the efficacy and safety of teriflunomide in reducing the frequency of relapses and progression of physical disability in patients with relapsing multiple sclerosis (RMS). Literatures were searched in Pubmed, Medline and Embase to screen citations from January 1990 to April 2015. Studies of parallel group design comparing teriflunomide and placebo for RMS were screened. After independent review of 234 citations by two authors, seven studies were identified as meeting the inclusion criteria. The results showed teriflunomide (7 and 14 mg) could significantly reduce annualized relapse rate and teriflunomide at the higher dose could also decrease the disability progression (risk ratio (RR) = 0.69, 95% confidence interval (CI): 0.55–0.87). And teriflunomide significantly reduce annualized rates of relapses with sequelae-EDSS/FS, relapses leading to hospitalization, and relapses requiring IV corticosteroids. Patients treated with teriflunomide 14 mg have a lower annualized rate of relapses with sequelae-investigator (RR = 0.37, 95% CI: 0.26–0.52). Teriflunomide 7 mg has a higher incidence of diarrhea (RR = 1.73, 95% CI: 1.32–2.26) and hair thinning (RR = 1.99, 95% CI: 1.4–2.81), while teriflunomide 14 mg has a higher incidence of diarrhea (RR = 1.71, 95% CI: 1.34–2.18), hair thinning (RR = 2.81, 95% CI: 2.02–3.91) and nausea (RR = 1.65, 95% CI: 1.03–2.31) compared with placebo. The incidence of elevated alanine aminotransferase levels was also higher with teriflunomide than with placebo. However, the incidence of serious adverse events was similar across groups. In conclusion, teriflunomide significantly reduces annualized relapse rates and disability progression with a similar safety and tolerability profile to placebo.     

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p < 0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p < 0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.     

Traumatic interhemispheric subdural haematoma: Study of 35 cases

The clinical and radiological findings, management, and outcomes in 35 patients with traumatic interhemispheric subdural haematoma (ISH) were reviewed retrospectively. Twenty-five patients had favourable outcomes and 10 had poor outcomes. All patients were treated conservatively for ISH. Univariate analysis found that the Glasgow Coma Scale (GCS) score (p < 0.001), hypovolemic shock (p = 0.018), skull fracture (p = 0.008), convexity or posterior fossa subdural haematoma (p = 0.008), and subarachnoid haemorrhage (SAH) were correlated with outcome (p < 0.001). Multivariate analysis showed that GCS score (p = 0.031; odds ratio [OR], 0.6; 95% confidence interval [CI], 0.3–0.9) and the presence of SAH (p = 0.023; OR, 14.2; 95% CI, 1.5–138.2) were significantly related to poor outcome. This study provides important information on the clinicoradiological findings and prognoses in patients with traumatic ISH.     

Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: Characterization of differential expression patterns in cerebral vasospasm

Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biomarkers and to better understand the pathogenesis of cerebral vasospasm. Nine female patients with aneurysmal subarachnoid hemorrhage underwent serial analysis of 239 different serum protein levels using quantitative, multiplexed immunoassays (DiscoveryMAP 250+ v2.0, Myriad RBM, Austin, TX, USA) on post-hemorrhage days 0 and 5. A repeated measures analysis of variance determined that mean protein concentration decreased significantly in patients who developed vasospasm versus those who did not for alpha-2-macroglobulin (F [1.00,7.00] = 16.33, p = 0.005), angiogenin (F [1.00,7.00] = 7.65, p = 0.028), apolipoprotein A-IV (F [1.00,7.00] = 6.308, p = 0.040), granulocyte colony-stimulating factor (F [1.00,7.00] = 9.08, p = 0.020), macrophage-stimulating protein (F [1.00,7.00] = 24.21, p = 0.002), tetranectin (F [1.00,7.00] = 5.46, p < 0.039), vascular endothelial growth factor receptor 3 (F [1.00,7.00] = 6.94, p = 0.034), and significantly increased for vitronectin (F [1.00,7.00] = 5.79, p = 0.047). These biomarkers may be of value in detecting cerebral vasospasm, possibly aiding in the identification of patients at high-risk prior to neurological deterioration.     

Minimally invasive surgery for primary supratentorial intracerebral haemorrhage

The use of minimally invasive surgery (MIS) in the treatment of primary supratentorial intracerebral haemorrhage (ICH) is controversial. This review was undertaken to combine all available evidence on this topic and to assess the efficacy of MIS compared to medical treatment or haematoma evacuation via craniotomy for patients with primary supratentorial ICH. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases were searched for randomised controlled trials which compared MIS to any control treatment for intracerebral haemorrhage. Conference proceedings, reference lists and internet-based clinical trial registries were searched for additional studies. Quality was assessed using the Cochrane “risk of bias” analysis tool. The methodological quality of studies was not high, with only two studies conforming to all quality standards assessed. There were 11 studies with 1717 patients. There was a significant reduction in relative risk (RR) for death at end of follow-up when MIS was compared to both medical management (RR = 0.67, 95% confidence interval 0.53–0.84) and craniotomy (RR = 0.57, 95% confidence interval 0.39–0.84) with no significant heterogeneity. Non-significant benefits were observed for the outcomes death or dependent survival (RR = 0.95, 95% confidence interval 0.91–1.00) and independent survival (RR = 1.24, 95% confidence interval 0.99–1.55). There was significant heterogeneity for both these outcomes. MIS for primary supratentorial ICH is associated with a significant reduction in the RR of death when compared to medical management and craniotomy. Other important outcomes need further evaluation.     

Metabolic syndrome and stroke: A meta-analysis of prospective cohort studies

Background and aimThe relationships between metabolic syndrome (MetS) and risk of incident stroke are inconsistent. We summarized the evidence by a meta-analysis of prospective cohort studies.Methods and resultsWe searched the PubMed, EMBASE, and Google Scholar databases from their inception until June 2016 for prospective cohort studies investigating this research question, relevant information was extracted by two independent investigators, and then aggregated using the fixed-effects models.We identified 16 studies, including 116,496 participants who were initially free of cardiovascular diseases. Comparing the persons without MetS, those with MetS have a significantly higher risk of incident stroke, and the pooled relative risk (RR) was 1.70 (95% confidence interval (CI): 1.49–1.95). Subgroup analyses suggested that women were more sensitive to this effect (with an RR of 1.83, 95% CI: 1.31–2.56) than men (RR = 1.47 (95% CI: 1.22–1.78). And those with MetS have a significantly higher risk of ischemic stroke (RR = 2.12, 95% CI: 1.46–3.08) than hemorrhagic stroke (RR = 1.48, 95% CI: 0.98–2.24).ConclusionsThis meta-analysis suggests that metabolic syndrome might be an important risk factor of stroke, particularly among women and those with ischemic stroke.     

In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA

Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007–2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p < 0.001), predominantly male (53.3% versus 38.5%, p < 0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p < 0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p < 0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p < 0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27–1.61, p < 0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69–0.87, p < 0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted.     

Should we treat patients with impaired consciousness and periodic patterns on EEG?

PurposeThe significance of periodic EEG patterns in patients with impaired consciousness is controversial. We aimed to determine if treating these patterns influences clinical outcome.MethodWe studied all patients who had periodic discharges on their EEG recordings from January 2007 to December 2009. Patients with clinical seizures within the preceding 24 h, or with unequivocal electrographical seizure activity were excluded. Logistic regression was performed to analyze for factors associated with (a) mortality (b) functional status (c) resolution of EEG pattern.ResultsOf the 4246 patients who had EEG, 111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted analysis, higher mortality was associated with acute symptomatic etiology (OR 17.74, 95% CI 1.61–196.07, p = 0.019), and presence of clinical seizures (OR 4.73, 95% CI 1.10–20.34, p = 0.037). For each unit decrement of GCS, the odds of inpatient mortality and a poorer functional state on discharge increased by 23% (95% CI 7–37%, p = 0.009) and 33% (95% CI 9–51%, p = 0.011) respectively. Administration of abortive therapy was an independent risk factor for poorer functional status on discharge (adjusted OR 41.39, 95% CI 2.88–594.42, p = 0.006), while patients with history of pre-existing cerebral disease appeared more likely to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI 1.40–17.86, p = 0.013).ConclusionTreatment of periodic EEG patterns does not independently improve clinical outcome of patients with impaired conscious levels. Occurrence of seizures remote to the time of EEG and lower GCS scores independently predict poor prognoses.     

Percutaneous endoscopic lumbar discectomy for lumbar disc herniation

This study aims to compare the advantages and disadvantage of percutaneous endoscopic lumbar discectomy (PELD) and standard discectomy (SD) for the treatment of lumbar intervertebral disc herniation (LDH). We searched in MEDLINE, EMBASE, PubMed, Web of Science and Cochrane databases for relevant trials that compare PELD and SD for the treatment of LDH. The Cochrane Collaboration’s Revman 5.3 software was used for data analyses. This meta-analysis compiled 1301 cases from four random controlled trials and three retrospective studies. Compared with SD, PELD showed a shorter operative time (mean difference (MD) = −18.68, 95% confidence interval (CI): −24.92 to −12.43; p < 0.00001), less blood loss (MD = −64.88, 95% CI: −114.51 to −15.25, p < 0.0001), shorter hospital stay (MD = −3.51, 95% CI: −4.93 to −2.08, p < 0.00001), and shorter mean disability period (MD = −34.34, 95% CI: −53.90 to −14.77, p < 0.006). However, there were no significant differences in the visual analogue scale (VAS) scores at the final follow up (MD = −0.23, 95% CI: −0.53 to 0.07, p = 0.14), Macnab criteria at the final follow up (MD = 1.04, 95% CI: 0.72 to 1.50, p = 0.82), complications (RR = 0.76, 95% CI: 0.40 to 1.43, p = 0.39), recurrence rate (risk ratio (RR) = 1.00, 95% CI: 0.61 to 1.64, p = 1) and reoperation rate (RR = 1.40, 95% CI: 0.90 to 2.16, p = 0.13). In conclusion, despite PELD showing significant benefit in short term outcomes such as hospital course and mean disability period, similar clinical efficacy and long term outcomes were observed when compared to SD. Therefore, we suggest that PELD can be a feasible alternative to the conventional posterior approach for the LDH depending on surgeon preference and indication. High-quality randomized controlled trials with sufficient large sample sizes necessary further confirm these results.     

Independent predictors of mortality following spine surgery

We investigated the effect of preoperative patient demographics and operative factors on mortality in the 30 day postoperative period after spine surgery. Postoperative mortality from surgical interventions has significantly decreased with progressive improvement in surgical techniques and patient selection. Well-studied preoperative risk factors include age, obesity, emphysema, clotting disorders, renal failure, and cardiovascular disease. However, the prognostic implications of such risk factors after spine surgery specifically remain unknown. The medical records of all consecutive patients undergoing spine surgery from 2008–2010 at our institution were reviewed. Patient demographics, comorbidities, indication for operation, surgical details, postoperative complications, and mortalities were collected. The association between preoperative demographics or surgical details and postoperative mortality was assessed via logistic regression analysis. All 1344 consecutive patients (1153 elective, 191 emergency) met inclusion criteria for the study; 19 (1.4%) patients died in the 30 days following surgery. Multivariable logistic regression found several predictive factors of mortality for all spine surgery patients: operation in the cervical area (odds ratio [OR]: 7.279, 95% confidence interval [CI]: 1.37–42.83, p = 0.02), postoperative sepsis (OR: 5.75, 95% CI: 1.16–26.38, p = 0.03), operation for neoplastic (OR: 7.68, 95% CI: 1.53–42.71, p = 0.01) or traumatic (OR: 13.76, 95% CI: 2.40–88.68, p = 0.03) etiology, and age as defined as a continuous variable (OR: 1.05, 95% CI: 1.01–1.10, p = 0.03). This study demonstrates predictive factors to help identify and evaluate patients who are at higher risk for mortality from spinal surgery, and potentially devise methods to reduce this risk.     

A meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures

A meta-analysis was conducted to assess the safety and efficacy of balloon kyphoplasty (KP) compared to percutaneous vertebroplasty (VP) in the treatment of osteoporotic vertebral compression fractures (OVCF). Ten studies, encompassing 783 patients, met the inclusion criteria. Overall, the results of the meta-analysis indicated that there were significant differences between the two groups in the long-term kyphosis angle (mean difference [MD] = –2.64, 95% confidence interval [CI] = –4.66 to –0.61; p = 0.01), the anterior height of the vertebral body (MD = 3.67, 95% CI = 1.40 to 5.94; p = 0.002), and the cement leakage rates (risk ratio [RR] = 0.70, 95% CI = 0.52 to 0.95; p = 0.02). However, there were no significant differences in the short-term visual analog scale (VAS) scores (MD = –0.57, 95% CI –1.33 to 0.20; p = 0.15), the long-term VAS scores (MD = –0.99, 95% CI = –2.29 to 0.31; p = 0.14), the short-term Oswestry Disability Index (ODI) scores (MD = –6.54, 95% CI = –14.57 to 1.48; p = 0.11), the long-term ODI scores (MD = –2.01, 95% CI = –11.75 to 7.73; p = 0.69), the operation time (MD = 4.47, 95% CI = –0.22 to 9.17; p = 0.06), the short-term kyphosis angle (MD = –2.25, 95% CI = –5.14 to 0.65; p = 0.13), or the adjacent-level fracture rates (RR = 1.52, 95% CI = 0.76 to 3.03; p = 0.24). This meta-analysis demonstrates that KP and VP are both safe and effective surgical procedures for treating OVCF. Compared with VP, KP can significantly relieve a long-term kyphosis angle, improve the height of the vertebral body, and reduce the incidence of bone cement leakage. However, because of the limitations of this meta-analysis, a large randomized controlled trial is required to confirm our findings.     

Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt–Hess grade 4–5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5–3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1–4.8), aneurysm size >10 mm (OR 1.7, 95% CI 1.1–2.6), body temperature ?38.3 °C (OR 2.5, 95% CI 1.1–5.4), and hyperglycemia >200 mg/dL (OR 2.7, 95% CI 1.6–4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt–Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes.     

A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme

Combining bevacizumab with irinotecan is a new chemotherapy regimen for patients with recurrent glioblastoma multiforme (GBM). Recent phase II trials suggest that this combined chemotherapy is beneficial to patients, but the subsequent adverse events may lead to treatment discontinuation. No comparison has yet demonstrated conclusively that the combined chemotherapy is more beneficial than single-agent chemotherapy. Thus, a meta-analysis was conducted to assess the efficacy and safety of bevacizumab compared to bevacizumab combined with irinotecan for the treatment of recurrent GBM. A total of 480 patients were included in the study, with 183 patients (38.1%) in the bevacizumab group and 297 patients (61.9%) in the bevacizumab plus irinotecan group. The median overall survival was 8.63 months (95% confidence interval [CI], 8.54–8.72 months) and 8.91 months (95% CI, 8.69–9.13 months), respectively. The mean objective response rate (complete response plus partial response rate) was 33.9% (95% CI, 18.1–52.1%) and 45.8% (95% CI, 28.2–66.7%), respectively. The 6-month progression-free survival rates (PFS-6) were 38.8% (95% CI, 18.8–57.0%) and 48.3% (95% CI, 25.4–54.3%), respectively. The rate of discontinuation was 5.5% and 20.0%, respectively. Compared with patients treated with bevacizumab only, those in the bevacizumab plus irinotecan group had higher PFS-6 (p = 0.046), objective response (p = 0.013) and rate of discontinuation (p = 0.000) but there was no statistically significant difference in overall survival between the groups (p = 0.487). Thus, although the combination of bevacizumab and irinotecan may increase the rate of discontinuation, it provided no obvious improvement in overall survival in patients with recurrent GBM. Therefore, the benefits of drug combination are outweighed by the treatment discontinuity and quality of life effects of drug toxicity and should be considered on an individual patient basis only.     

Carotid artery disease and perioperative stroke risk after surgical aortic valve replacement: A nationwide inpatient sample analysis

To study the role of carotid stenosis (CS) and cerebrovascular disease as independent risk factors for perioperative stroke following surgical aortic valve replacement (SAVR). The National Inpatient Sample (NIS) database was used for our study. All patients who underwent SAVR from 1999 to 2011 were identified using ICD-9 codes. Univariate and multivariate analysis of baseline characteristics, Elixhauser comorbidities and other covariates were examined to identify independent predictors of perioperative strokes following SAVR. Data on 50,979 patients who underwent SAVR from 1999 to 2011 was obtained. The mean age of the study cohort was 60.5. The study patients were predominantly Caucasian (79.3%) and males (60.01%). The incidence of perioperative stroke was 2.48%. CS (OR 1.8, 95%CI 1.1–2.8, p = 0.009) and cerebral arterial occlusion (OR 3.4, 95% CI 1.3–8.9) significantly increased perioperative stroke risk following SAVR. Infective endocarditis (OR 4.6, 95%CI 3.8–5.6, p = 0.00) and neurological disorders (OR 4.8, 95% CI 4–5.8, p = 0.00) appeared to be the strongest risk factors for strokes. Other risk factors found to be significant predictors of perioperative strokes (p < 0.05) were – age, higher VWR scores, CS, cerebral arterial occlusion, infective endocarditis, DM, HTN, renal failure, neurological disorders, coagulopathy and hypothyroidsm. In conclusion, perioperative stroke risk has remained more or less constant despite advancements in surgical techniques with risk having gone up in patients <65 years of age. CS and cerebral arterial occlusion significantly increase stroke risk following SAVR. Improved patient selection with pre-operative risk stratification and institution of preventive strategies are necessary to improve operative outcomes following SAVR.     

Angiotensin-converting enzyme-inhibitors,statins and the risk of hemorrhage from cerebral dural arteriovenous fistulae

Leptomeningeal venous drainage and symptomatic presentation are known risk factors for cerebral dural arteriovenous fistula (dAVF) hemorrhage. An evaluation of potentially modifiable risk factors such as hypertension and medication usage has not been undertaken to our knowledge. The authors thus reviewed a cohort of 45 consecutive patients with cerebral dAVF with leptomeningeal venous drainage and compared the rate of hemorrhagic presentation for patients with and without a history of hypertension, hyperlipidemia or the usage of certain medications. Logistic regression was performed to determine the statistical significance of associations of each factor with hemorrhagic presentation. On univariate analysis, angiotensin-converting enzyme (ACE)-inhibitors (odds ratio [OR] 0.100, 95% confidence interval [CI] 0–0.764, p = 0.024) and statins (OR 0.142, 95% CI 0.025–0.825, p = 0.030) were associated with a statistically significant lower rate of hemorrhagic presentation. A trend toward a lower rate of hemorrhagic presentation was seen for patients taking aspirin (OR 0.153, 95% CI 0.016–1.43, p = 0.10). These trends continued on multivariate analysis; however they did not meet statistical significance (p > 0.05). Beta-blockers, calcium channel blockers, warfarin and selective serotonin reuptake inhibitors did not have a statistically significant association with the rate of hemorrhagic presentation (p > 0.05). Although limited by small sample size, these results may suggest a beneficial effect of statins and ACE-inhibitors on the rate of dAVF hemorrhagic presentation, potentially as a result of anti-inflammatory, anti-angiogenic or even venous antithrombotic mechanisms. Despite this study’s limitations, we hope it encourages further evaluation of potentially modifiable risk factors for vascular malformation hemorrhage.     

Performance status during and after radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma multiforme

For elderly patients with glioblastoma multiforme (GBM), radiotherapy plus concomitant and adjuvant temozolomide has resulted in longer survival. We investigated patient performance status, treatment-related toxicity and overall survival (OS) following treatment. Twenty patients aged 70 years or older with a newly diagnosed GBM were treated with radiotherapy (60 Gy in 16 patients and 40 Gy in four patients) plus concomitant and adjuvant temozolomide. We assessed age, the extent of tumor removal, and initial performance status as possible prognostic factors for OS and good performance status following treatment. The median OS was 11.8 months (95% confidence interval [CI], 8.7–14.8). The median time for patients to reach an Eastern Cooperative Oncology Group (ECOG) performance status grade 2 was 3.0 months (95% CI, 2.4–3.5), and the time to ECOG performance status grade 3 was 5.8 months (95% CI, 1.6–9.9). World Health Organization grade III or grade IV toxicity was observed in four patients (20%), leucopenia and thrombocytopenia was noted in two patients, and major infection occurred in two patients. Univariate analysis showed a significantly longer OS (p = 0.003) and a longer time with good performance status for gross total removal (GTR) (p = 0.003). An initial good performance status was related to a good performance status during and after treatment (p = 0.003). Based on multivariate analysis, GTR was significantly associated with a longer OS (hazard ratio [HR] = 0.236; 95% CI, 0.060–0.922, p = 0.038) and a good performance status (HR = 0.124; 95% CI, 0.022–0.693, p = 0.017). During and after treatment, elderly patients with GBM frequently exhibited an early deterioration of performance status. Therefore, in light of a rapidly fatal illness, elderly patients should be treated to preserve and respect their quality of life.     

Risk factors for calcification of the vertebrobasilar arteries in cardiovascular patients referred for a head CT,the SMART study

Background and purposeVertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan.Materials and methodsAll patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤ 0.90, ≥ 1.30, continuous), internal carotid artery stenosis ≥ 70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex.ResultsOf the 471 patients included (57% male, median age 58 [interquartile range 47–63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years = 1.70 [95%CI 1.46–1.99]), DM (RR = 1.45 [95%CI 1.03–2.06]), obesity (RR = 1.53 [95%CI 1.10–2.12]), ABI ≤ 0.90 (RR = 1.57 [95%CI 1.02–2.41]), and an increased carotid IMT (RR = 2.60 per mm [95%CI 1.20–5.62]). Other measurements were not associated with VBAC.ConclusionsWe identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention.