Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older.

OBJECTIVE: We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. METHODS: We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3-6 at discharge) and mortality using multivariable analysis. RESULTS: The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2-1.7) despite a lower proportion of poor outcomes (0.84, 0.75-0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17-0.24), statin (0.63, 0.50-0.79), ozagrel sodium (0.72, 0.60-0.86), and cilostazol (0.63, 0.51-0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51-0.68), statin (0.84, 0.75-0.94), and EPA (0.83, 0.72-0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. CONCLUSIONS: In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

Inhibition of glioblastoma cell invasion by hsa-miR-145-5p and hsa-miR-31-5p co-overexpression in human mesenchymal stem cells.

OBJECTIVE: Human bone marrow­derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. METHODS: To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells. RESULTS: In coculture, hMSCs cotransfected with hsa-miR-145-5p and -31-5p miRNAs showed markedly reduced invasion by U87 glioma cells in a contact-dependent manner both in vitro and ex vivo, with invasion of hMSCs cotransfected with these 2 miRNAs by the U87 cells reduced to 60.7% compared with control cells. According to a Matrigel invasion assay, the tropism of the hMSCs for U87 cells was not affected. In glioma cell lines U251 and LN229, hMSCs exhibited tropism in vivo, and invasion of hMSCs cotransfected with hsa-miR-145-5p and -31-5p was also significantly less than that of control cells. When U87 cells were coimplanted into the striatum of organotypic rat brain slices with hMSCs cotransfected with hsa-miR-145 and -31-5p, the relative invasive area decreased by 37.1%; interestingly, these U87 cells showed a change to a rounded morphology that was apparent at the invasion front. Whole-genome microarray analysis of the expression levels of 58,341 genes revealed that the co-overexpression of hsa-miR-145-5p and -31-5p downregulated FSCN1 expression in U87 cells. CONCLUSIONS: This study demonstrates that miRNA overexpression in hMSCs can alter the function of glioma cells via contact-dependent transfer. Co-overexpression of multiple miRNAs may be a useful and novel therapeutic strategy. The study results suggest that hMSCs can be applied as a delivery vehicle for miRNAs.

[Usefulness of image fusion for the treatment guidance of cavernous sinus dural arteriovenous fistula].

Before treating an arteriovenous fistula, it is important to understand its features, particularly the shunting point, sinus form, and drainage route. However, this can often be difficult owing to the large number of vessels that accumulate in the fistula region. In this study, we employed image fusion technology to understand the pathology of cavernous sinus dural arteriovenous fistulas (CSdAVFs) prior to treatment. We performed the following three types of fusions on the workstation: three-dimensional rotation angiography (3DRA) images from different feeding arteries to gain a detailed understanding of fistula architecture and shunting points; three-dimensional computed tomography (3DCT) and 3DRA images for determining the correlation between the skull base bone and the sinus shunt to predict the point of shunt access;and time-of-flight magnetic resonance imaging (TOF MRI) scans and 3DRA source images for investigating retrograde leptomeningeal venous drainage. Compared to individual images, the fused images more effectively provided a detailed understanding of CSdAVFs. Herein, we report our experience with image fusion for CSdAVF and review the relevant literature.