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Intraoperative MRI versus 5-ALA in high-grade glioma resection: a network meta-analysis

Danielle Golub, Jonathan Hyde, Siddhant Dogra, Joseph Nicholson, Katherine A. Kirkwood, Paulomi Gohel, Stephen Loftus, and Theodore H. Schwartz

OBJECTIVE

High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence.

METHODS

PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models.

RESULTS

This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65–9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127–3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905–3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival.

CONCLUSIONS

IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.

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Treatment of chronic subdural hematoma with atorvastatin combined with low-dose dexamethasone: phase II randomized proof-of-concept clinical trial

Dong Wang, Chuang Gao, Xin Xu, Tao Chen, Ye Tian, Huijie Wei, Shu Zhang, Wei Quan, Yi Wang, Shuyuan Yue, Zengguang Wang, Ping Lei, Craig Anderson, Jingfei Dong, Jianning Zhang, and Rongcai Jiang

OBJECTIVE

The authors sought to test the hypothesis that adding dexamethasone (DXM) to atorvastatin (ATO) potentiates the effects of ATO on chronic subdural hematoma (CSDH).

METHODS

Sixty patients with CSDH underwent 5 weeks of treatment with an additional 7-week follow-up. Patients were randomized to receive a 5-week regimen of ATO 20 mg daily or ATO 20 mg daily plus a DXM regimen (ATO+DXM). The 5-week DXM regimen was 2.25 mg daily for 2 consecutive weeks, followed by 0.75 mg twice daily for 2 weeks and 0.75 mg once daily for 1 week. The primary endpoint was hematoma reduction assessed by neuroimaging at baseline and at 5 weeks of follow-up. Secondary outcomes included neurological improvement assessed by using the Markwalder’s Grading Scale and Glasgow Coma Scale (MGS-GCS).

RESULTS

The mean patient age was 66.6 years, and 25% of patients were women. The patients who were treated with ATO+DXM had more obvious hematoma reduction at the 5th week (between-groups difference 18.37 ml; 95% CI 8.17–28.57; p = 0.0005). This reduction started from the 2nd week (14.51 ml; 95% CI 4.31–24.71; p = 0.0056) of treatment and persisted until the 12th week (17.50 ml; 95% CI 7.30–27.70; p = 0.0009). Complete recovery of neurological function (MGS-GCS grade 0) at 5 weeks was achieved in 83.33% and 32.14% of patients in the ATO+DXM and ATO groups, respectively. At the 5th week, patients receiving ATO+DXM had significantly lower levels of T cells and higher levels of regulatory T cells and endothelial progenitor cells in their peripheral blood.

CONCLUSIONS

ATO+DXM was more effective than ATO alone in reducing hematoma and improving neurological function in patients with CSDH. These results require further confirmation in a randomized placebo-controlled trial.

Clinical trial registration no.: ChiCTR-IPR-14005573 (http://www.chictr.org.cn/index.aspx)