Glioblastoma (GBM) is the most highly malignant brain tumor in the human central nerve system. In this paper, we review new and significant molecular findings on angiogenesis and possible resistance mechanisms. Expression of a number of genes and regulators has been shown to be upregulated in GBM microvessel cells, such as interleukin-8, signal transducer and activator of transcription 3, Tax-interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2. The regulator factors that may strongly promote angiogenesis by promoting endothelial cell metastasis, changing the microenvironment, enhancing the ability of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are reviewed. Based on the current knowledge, several potential targets and strategies are proposed for better therapeutic outcomes, such as its mRNA interference of DII4-Notch signaling pathway and depletion of b1 integrin expression. We also discuss possible mechanisms underlying the resistance to anti-angiogenesis and future directions and challenges in developing new targeted therapy for GBM.

IntroductionAcute basilar artery occlusion (BAO) can result in extremely high disability and mortality. Stent retrievers (SRs) can achieve a high recanalization rate for BAO, therefore improving favorable outcomes. However, the efficacy of a direct aspiration first pass technique (ADAPT) to treat BAO is unclear. Our aim was to compare the efficacy and safety of firstline ADAPT with that of firstline SR for patients with acute BAO.MethodsThree databases were systematically searched for literature reporting outcomes on thrombectomy for acute BAO with both firstline ADAPT and firstline SR. The modified Newcastle–Ottawa scale was applied to assess bias risk. The random effects model was used.ResultsOf 50 articles, 5 cohort studies (2 prospective and 3 retrospective) were included in our research. 193 cases were treated with firstline ADAPT and 283 cases received firstline SR. Successful recanalization rate was significantly higher in the firstline ADAPT group (OR=2.0, 95% CI 1.1 to 3.5). Procedure time (mean difference=−27.6 min, 95% CI −51.0 to −4.3) and the incidence of new territory embolic event (OR=0.2, 95% CI 0.05 to 0.83) was significantly less in the firstline ADAPT group. No significant difference was observed between the firstline ADAPT and firstline SR groups for rate of complete recanalization, rescue therapy, any hemorrhagic complication, favorable outcomes, or mortality at 90 days.ConclusionsOur meta-analysis suggested that for patients with acute BAO, firstline ADAPT might achieve higher and faster recanalization, comparable neurological improvement and safety compared with firstline SR. Further studies are needed to confirm these results.

Flow diverter devices (FDDs) are increasingly used in the treatment of intracranial aneurysm. The safety and feasibility of FDD were assessed in published literature. In accordance with strict inclusion criteria, Medline, Embase, Cochrane, China National Knowledge Infrastructure, and Web of Science databases were searched for literature that covers a period until February 2015. The baseline characteristics of patients, aneurysms, aneurysm occlusion, morbidity, and mortality were also collected. A meta-analysis was conducted using STATA 12.0, and a chi-squared test was performed to evaluate whether statistically significant differences existed between complications and mortality of aneurysm patients. Finally, a total of 48 studies were selected, including 2508 patients with 2826 aneurysm cases. The mean follow-up interval is 6.3 months, and the aneurysm occlusion rate is 77.9 % (95 % CI 73.8-81.9, I (2) = 43.4 %). The total morbidity and mortality rates are 9.8 and 3.8 %, respectively. The rates of spontaneous rupture and intraparenchymal hemorrhage are 2.0 and 2.5 %, respectively. The rate of ischemic stroke is 5.5 %. The morbidity and mortality rates of giant aneurysms are significantly higher than those of small and large aneurysms (χ (2) = 56.96, p < 0.05; χ (2) = 14.88, p < 0.05). The morbidity rates of posterior aneurysms are significantly higher than those of anterior (χ (2) = 11.29, p < 0.05) and unruptured aneurysms (χ (2) = 10.36, p < 0.05), respectively. The publication bias of aneurysm occlusion was detected by Begg's rank, and the corrected result is less than 0.05. Our meta-analysis suggests that the treatment of intracranial aneurysm with FDD is feasible and effective with a high occlusion rate, acceptable morbidity, and mortality. However, the morbidity or mortality of giant aneurysms is still high.

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Purpose Diabetes mellitus indicated poor clinical prognosis for patients with acute ischemic stroke. Furthermore, diabetes mellitus could also impact the hemostatic system, while its influence on the histological composition of thrombus is unclear. Methods Consecutive patients with retrieved clots were included. Histologic staining for thrombus included hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor. The differences in clot composition were compared according to diabetes mellitus history or hyperglycemia (≥7.8 mmol/L) on admission. Results A total of 52 patients were included; half of them were diagnosed as diabetes mellitus previously. Diabetic patients showed higher serum glucose on admission (8.90 vs. 7.40, p = 0.012). The baseline characteristics (expect smoking history and thrombus location), procedural, and clinical outcomes were similar between diabetic patients and nondiabetic patients. As for histologic composition, thrombus in patients with diagnosed diabetes mellitus had more fibrin (44.2% vs. 28.3%, p = 0.004) and fewer red blood cells (26.0% vs. 42.9%, p = 0.013) and equivalent content of platelets (24.0% vs. 21.5%, p = 0.694) and von Willebrand factor (0.041 vs. 0.031, p = 0.234) than patients without diabetes mellitus. However, there was no statistical difference in the content of red blood cells (41.6% vs. 27.3%, p = 0.105), fibrin (37.6% vs. 34.3%, p = 0.627), platelets (21.2% vs. 24.2%, p = 0.498), and von Willebrand factor (0.038 vs. 0.034, p = 0.284) between patients with or without hyperglycemia on admission. Conclusion Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results.

Objective: Although the benefits of good collateral circulation on infarct volume and outcomes have been confirmed in previous studies, few studies have investigated the relationship between hemorrhagic transformation (HT) and collateral circulation in acute ischemic stroke (AIS). This study aimed to assess whether collateral circulation is an essential factor of HT after endovascular treatments (EVTs).Methods: In total, 71 consecutive AIS patients who underwent EVTs between July 2015 and February 2019 were retrospectively studied. The correlations among HT, collateral vessels on 4D CT angiography (4D CTA), and other predictive factors for HT [e.g., National Institutes of Health Stroke Scale (NIHSS) score, age, sex, serum glucose, and atrial fibrillation history] were evaluated by logistic regression analysis.Results: The rate of hemorrhagic transformation was 42.3% (30/71) in AIS patients. Multivariate logistic regression showed that a good collateral status (OR 0.76, 95% CI 0.73-0.80) was associated with a lower risk of HT. History of atrial fibrillation (OR 2.35, 95% CI 1.96-2.82), baseline NIHSS scores (OR 2.00, 95% CI 1.72-2.32), and higher serum glucose levels (OR 1.70, 95% CI 1.57-1.85) were all independent risk factors of HT.Conclusions: Patients with poor collateral circulation are at a higher risk of HT after receiving endovascular therapy. Thus, variations in collateral circulation based on 4D CTA may be an important factor for personalized clinical treatments. In addition, high blood glucose, atrial fibrillation and the baseline NIHSS score are all important independent predictors of HT.

Purpose This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients. Methods Consecutive patients with AIS due to large artery occlusion in the anterior circulation treated with mechanical thrombectomy (MT) were enrolled in a tertiary stroke center. Demographic and medical history data, admission lab results, and Circle of Willis (CoW) variations were collected from all patients. Results Altogether, 90 patients were included in this study; among them, 34 (37.8%) had HT after MT. The final pruned decision tree (DT) model consisted of collateral score and platelet to lymphocyte ratios (PLR) as predictors. Confusion matrix analysis showed that 82.2% (74/90) were correctly classified by the model (sensitivity, 79.4%; specificity, 83.9%). The area under the ROC curve (AUC) was 81.7%. The DT model demonstrated that participants with collateral scores of 2–4 had a 75.0% probability of HT. For participants with collateral scores of 0–1, if PLR at admission was <302, participants had a 13.0% probability of HT; otherwise, participants had an 75.0% probability of HT. The final adjusted multivariate logistic regression analysis indicated that collateral score 0–1 (OR, 10.186; 95% CI, 3.029–34.248; p < 0.001), PLR (OR, 1.005; 95% CI, 1.001–1.010; p = 0.040), and NIHSS at admission (OR, 1.106; 95% CI, 1.014–1.205; p = 0.022) could be used to predict HT. The AUC for the model was 0.855, with 83.3% (75/90) were correctly classified (sensitivity, 79.4%; specificity, 87.3%). Less patients with HT achieved independent outcomes (mRS, 0–2) in 90 days (20.6% vs. 64.3%, p < 0.001). Rate of poor outcomes (mRS, 4–6) was significantly higher in patients with HT (73.5% vs. 19.6%; p < 0.001). Conclusion Both the DT model and multivariate logistic regression model confirmed that the lower collateral status and the higher PLR were significantly associated with an increased risk for HT in AIS patients after MT. PLR may be one of the cost-effective and practical predictors for HT. Further prospective multicenter studies are needed to validate our findings.