In-hospital mortality and poor outcome after surgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage using nationwide databases: a systematic review and meta-analysis.

There has never been evidence for aneurysmal subarachnoid hemorrhage (aSAH) by endovascular coiling compared to surgical clipping with all grade. The present study and meta-analysis aimed to clarify the in-hospital mortality and poor outcome in the nationwide databases of patients with all grade aSAH between them. The outcome of modified Rankin scale (mRS) at discharge was investigated according to the comprehensive nationwide database in Japan. The propensity score-matched analysis was conducted among patients with aSAH in this database registered between 2010 and 2015. Meta-analysis of studies was conducted based on the nationwide databases published from 2007 to 2018. According to this propensity score-matched analysis, no significant association for poor outcome of mRS > 2 was shown between surgical clipping and endovascular coiling (47.7% vs 48.3%, p = 0.48). However, significantly lower in-hospital mortality was revealed after surgical clipping than endovascular coiling (7.1% vs 12.2%, p < 0.001). Meta-analysis of propensity score-matched analysis in the nationwide database showed no significant association for poor outcome at discharge between them (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.93 to 1.26; p = 0.31). Meta-analysis of propensity score-matched analysis for in-hospital mortality was lower after surgical clipping than after endovascular coiling, however, without significant difference (OR, 0.74; 95% CI, 0.52 to 1.04; p = 0.08). Further prospective randomized controlled study with all grade aSAH should be necessary to validate the in-hospital mortality and poor outcome.

Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Mechanisms underlying increased vascular smooth muscle contractility in the rabbit basilar artery following subarachnoid hemorrhage.

Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Here, we summarize our current knowledge regarding molecular mechanisms that contribute to increased smooth muscle contractility of rabbit basilar artery following SAH. Our studies demonstrated that upregulation of receptor expression, impairment of feedback regulation of receptor activity, and enhancement of myofilament Ca²âº sensitization might lead to increased smooth muscle contractility following SAH.

Ten-year national trends in in-hospital mortality and functional outcomes after intracerebral hemorrhage by age in Japan: J-ASPECT study.

INTRODUCTION: National-level data on trends in the prognosis of age-stratified patients with intracerebral hemorrhage (ICH) are lacking. This study aimed to assess time trends in in-hospital mortality and functional outcomes of ICH patients by sex and age, and to explore factors associated with changes in in-hospital mortality trend. PATIENTS AND METHODS: Using the largest nationwide, J-ASPECT stroke database in Japan, this serial cross-sectional study included ICH patients aged ⩾18 years who were hospitalized for non-traumatic ICH from April 2010 to March 2020. We examined trends in in-hospital mortality and functional outcomes using the modified Rankin Scale at discharge, as well as differences in in-hospital mortality change between age groups. RESULTS: Among 262,399 ICH patients from 934 hospitals, crude in-hospital mortality showed a significant decreasing time trend (from 19.5% to 16.7%), and this trend was consistent across sex and age groups. In addition, differences in in-hospital mortality change over the 10-year study period were significant between male patients aged ⩾75 years and those aged ⩽64 years (-3.9% [95% confidence interval, -5.4 to -2.4] for 75-84 years; -4.1% [-6.3 to -1.9] for ⩾85 years). On the other hand, the proportion of dependent patients (mRS 3-5) at discharge increased from 52.0% to 54.9% over the 10-year study period. CONCLUSION: The in-hospital mortality of ICH patients improved, whereas the proportion of patients with dependent functional outcome at discharge increased, over the 10-year study period. Elucidating the mechanism underlying differences in in-hospital mortality reduction in men may provide insights into effective interventions in the future.

Midline Suboccipital Unilateral Trans-Cerebellomedullary Fissure Approach for Clipping of Ruptured VA-PICA Aneurysm: Two-Dimensional Operative Video.

The vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysm poses a technical challenge for microsurgical clipping due to its anatomical complexity, which requires dissection of lower cranial nerves. Endovascular treatment is regarded as a feasible first-line therapeutic option for VA-PICA aneurysm because it has an acceptable aneurysm occlusion rate and is less invasive. However, microsurgical clipping remains an effective treatment option. We present the case of a 62-year-old man who presented with subarachnoid hemorrhage (SAH) due to a ruptured VA-PICA aneurysm. Neuroradiologic examination revealed a 2-3 mm medially pointing left VA-PICA aneurysm with acute obstructive hydrocephalus due to massive SAH in the posterior cranial fossa. As the patient had acute obstructive hydrocephalus and a relatively small aneurysm, we selected clipping over endovascular treatment. Because the aneurysm was located close to the midline and anterolateral to the medulla oblongata, we approached it from the midline. A midline suboccipital craniotomy, C1 laminectomy, and drilling of the left condylar fossa were performed; a unilateral cerebellomedullary fissure opening was added; and the aneurysm was clipped. Postoperative neuroradiologic examinations revealed complete obliteration of the aneurysm. As shown in this video, unilateral cerebellomedullary fissure opening combined with adequate removal of the condylar fossa provides a wide operative field in the cerebellomedullary cistern while avoiding strong retraction of the cerebellum. We believe that this technique makes VA-PICA aneurysm clipping safe and successful. Patient consent was obtained to perform the surgery and to publish the surgical video (Video 1).

Percutaneous transluminal angioplasty for persistent primitive hypoglossal artery stenosis: illustrative case.

BACKGROUND: We report a case of symptomatic, progressive stenosis of a persistent primitive hypoglossal artery (PPHA), which was successfully treated with percutaneous transluminal angioplasty (PTA) of the origin of the PPHA. The PPHA is a type of carotid-basilar anastomosis with an incidence of 0.02% to 0.10%. It originates from the internal carotid artery (ICA), passes through the hypoglossal canal, and merges with the basilar artery. In many cases, the ipsilateral vertebral artery is hypoplastic; therefore, PPHA stenosis causes cerebral infarction in the posterior circulation territory, as in this case. OBSERVATIONS: The patient's right PPHA had severe and progressive stenosis; therefore, he experienced cerebral infarction despite medical treatment. Therefore, PTA for the stenosis was performed, which ceased the recurrence of cerebral infarction and dizziness by improving blood flow in the posterior circulation. LESSONS: Several reports have described ICA stenosis accompanied by PPHA or PPHA stenosis in patients receiving endovascular treatments. Almost all cases were nonprogressive, and the treatment procedure was stenting. However, in our case, the PPHA stenosis was progressive, and we performed PTA because the patient experienced resistance to antiplatelet drugs and had poor collateral flow.

A cavernous sinus dural arteriovenous fistula treated by direct puncture of the superior ophthalmic vein with craniotomy: illustrative case.

BACKGROUND: The authors report a case of symptomatic cavernous sinus (CS) dural arteriovenous fistula (dAVF) that was successfully treated using direct puncture of the superior ophthalmic vein (SOV) with craniotomy. CS dAVF is commonly treated using transvenous embolization (TVE), with the most common access route via the inferior petrosal sinus (IPS). However, this route is sometimes unavailable because of an occluded, hypoplastic, aplastic, or tortuous IPS. The SOV is an alternative, albeit tortuous and long, route to the CS; therefore, direct SOV puncture is occasionally performed. Direct SOV puncture is mostly percutaneous; however, in this case, it was difficult because of subcutaneous SOV narrowing. OBSERVATIONS: As the patient experienced increased intraocular pressure, decreased vision, and eye movement disorders, CS embolization was performed via direct puncture with a craniotomy because of other access difficulties. LESSONS: Several reports have described CS dAVF in patients receiving endovascular treatment via direct SOV puncture using a transorbital approach. However, to the best of the authors' knowledge, this is the first reported case of a CS dAVF treated using TVE with craniotomy. This approach is useful when the SOV cannot be reached intravenously and its distance from the epidermis is long.

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study.

OBJECTIVES: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. DESIGN: Retrospective study. SETTING: Six hundred and thirty-one primary care institutions in Japan. PARTICIPANTS: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points). RESULTS: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. CONCLUSIONS: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Efficacy of combined use of a stent retriever and aspiration catheter in mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: The efficacy of combined stent retriever (SR) and aspiration catheter (AC; combined technique: CBT) use for acute ischemic stroke (AIS) is unclear. We investigated the safety and efficacy of single-unit CBT (SCBT)-retrieving the thrombus as a single unit with SR and AC into the guide catheter-compared with single use of either SR or contact aspiration (CA). METHODS: We analysed 763 consecutive patients who underwent mechanical thrombectomy for AIS between January 2013 and January 2020, at six comprehensive stroke centers. Patients were divided into SCBT and single device (SR/CA) groups. The successful recanalization with first pass (SRFP) and other procedural outcomes were compared between groups. RESULTS: Overall, 240 SCBT and 301 SR/CA (SR 128, CA 173) patients were analyzed. SRFP (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2c, 43.3% vs 27.9%, p<0.001; mTICI 3, 35.8% vs 25.5%, p=0.009) and final mTICI ≥2b recanalization (89.1% vs 82.0%, p=0.020) rates were significantly higher, puncture-to-reperfusion time was shorter (median (IQR) 43 (31.5-69) vs 55 (38-82.2) min, p<0.001), and the number of passes were fewer (mean±SD 1.72±0.92 vs 1.99±1.01, p<0.001) in the SCBT group. Procedural complications were similar between the groups. In subgroup analysis, SCBT was more effective in women, cardioembolic stroke patients, and internal carotid artery and M2 occlusions. CONCLUSIONS: SCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.

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.

Effects of case volume and comprehensive stroke center capabilities on patient outcomes of clipping and coiling for subarachnoid hemorrhage.

OBJECTIVE: Improved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH. METHODS: The authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1-25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH. RESULTS: Overall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55-0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53-0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59-0.96 vs Q4 OR 0.65, 95% CI 0.51-0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54-0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes. CONCLUSIONS: The effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

Microsurgical Anatomy of the Jugular Process as an Anatomical Landmark to Access the Jugular Foramen: A Cadaveric and Radiological Study.

BACKGROUND: The jugular process forms the posteroinferior surface of the jugular foramen and is an important structure for surgical approaches to the foramen. However, its morphological features have not been well described in modern texts. OBJECTIVE: To elucidate the microsurgical anatomy of the jugular process and examine its morphological features. METHODS: Five adult cadaveric specimens were dissected in a cadaveric study, and computed tomography data from 31 heads (62 sides) were examined using OsiriX (Pixmeo SARL, Bernex, Switzerland) to elucidate the morphological features of the jugular process. RESULTS: The cadaveric study showed that it has a close relationship with the sigmoid sinus, jugular bulb, rectus capitis lateralis, lateral atlanto-occipital ligament, and lateral and posterior condylar veins. The radiographic study showed that 9/62 sigmoid sinuses protruded inferiorly into the jugular process and that in 5/62 sides, this process was pneumatized. At the entry of the jugular foramen, if the temporal bone has a bulb-type jugular bulb, and if surgery concerns the right side of the head, the superior surface of the jugular process is more likely to be steep. CONCLUSION: The jugular process forms the posteroinferior border of the jugular foramen. Resection of the jugular process is a critical step for opening the jugular foramen from the posterior and lateral aspects. Understanding the morphological features of the jugular process, and preoperative and radiographical examination of this process thus help skull base surgeons to access the jugular foramen.

The Influence of Age on the Outcomes of Traumatic Brain Injury: Findings from a Japanese Nationwide Survey (J-ASPECT Study-Traumatic Brain Injury).

BACKGROUND: The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients. METHODS: Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients. RESULTS: Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P < 0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at >7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P < 0.001), and incidence of acute subdural hematoma (OR, 1.89; P < 0.001) were associated with in-hospital mortality in elderly patients with TBI. CONCLUSIONS: Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

National trends in outcomes of ischemic stroke and prognostic influence of stroke center capability in Japan, 2010-2016.

BACKGROUND: Limited national-level information on temporal trends in comprehensive stroke center capabilities and their effects on acute ischemic stroke patients exists. AIMS: To examine trends in in-hospital outcomes of acute ischemic stroke patients and the prognostic influence of temporal changes in comprehensive stroke center capabilities in Japan. METHODS: This retrospective study used the J-ASPECT Diagnosis Procedure Combination database and identified 372,978 acute ischemic stroke patients hospitalized in 650 institutions between 2010 and 2016. Temporal trends in patient outcomes and recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy usage were examined. Facility comprehensive stroke center capabilities were assessed using a validated scoring system (comprehensive stroke center score: 1-25 points) in 2010 and 2014. The prognostic influence of temporal comprehensive stroke center score changes on in-hospital mortality and poor outcomes (modified Rankin Scale: 3-6) at discharge were examined using hierarchical logistic regression models. RESULTS: Over time, stroke severity at admission decreased, whereas median age, sex ratio, and comorbidities remained stable. The median comprehensive stroke center score increased from 16 to 17 points. After adjusting for age, sex, comorbidities, consciousness level, and facility comprehensive stroke center score, proportion of in-hospital mortality and poor outcomes at discharge decreased (from 7.6% to 5.0%, and from 48.7% to 43.1%, respectively). The preceding comprehensive stroke center score increase (in 2010-2014) was independently associated with reduced in-hospital mortality and poor outcomes, and increased rt-PA and mechanical thrombectomy use (odds ratio (95% confidence interval): 0.97 (0.95-0.99), 0.97 (0.95-0.998), 1.07 (1.04-1.10), and 1.21 (1.14-1.28), respectively). CONCLUSIONS: This nationwide study revealed six-year trends in better patient outcomes and increased use of rt-PA and mechanical thrombectomy in acute ischemic stroke. In addition to lesser stroke severity, preceding improvement of comprehensive stroke center capabilities was an independent factor associated with such trends, suggesting importance of comprehensive stroke center capabilities as a prognostic indicator of acute stroke care.

Relationship Between the Horizontal Part of the Sigmoid Sinus and the Line Through the Digastric Point and Posterior Edge of the Condyle: An Anatomic and Radiologic Study.

OBJECTIVE: This study aims to determine whether the line between the digastric point and posterior edge of the occipital condyle (DC line) could be a new surface landmark for the posterior margin of the horizontal part of the sigmoid sinus. METHODS: Cadaveric specimens were used to show the relationship between the DC line and retrosigmoid craniotomy. Three-dimensional computed tomography angiography images of adult heads (56 sides) were analyzed to measure the distance between the DC line and the horizontal part of the sigmoid sinus at the digastric point, posterior edge of the condyle, and midpoint of the line. RESULTS: The DC line was roughly parallel and posterior to the posterior margin of the sigmoid sinus. The distance between the DC line and the posterior edge of the sigmoid sinus at the digastric point, condyle, and midpoint of the line measured 4.7 ± 3.3 mm, 5.9 ± 2.6 mm, and 1.3 ± 2.2 mm, respectively. All sigmoid sinuses coursed anterior to the digastric point and condyle but in 17.9% (10/56 sides) the posterior edge of the sigmoid sinus extended a maximum of 4.1 mm posterior to the midpoint of the DC line. CONCLUSIONS: The DC line can be used as a new surface landmark for estimating the position of the horizontal part of the sigmoid sinus. The posterior edge of the sinus may extend posterior to the line at the midpoint; thus, care should be taken to prevent sinus injury when drilling around the midpoint of the line.

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.

Surgical Anatomy of the Eustachian Tube for Endoscopic Transnasal Skull Base Surgery: A Cadaveric and Radiologic Study.

OBJECTIVE: The endoscopic endonasal approach to the anatomically complex lateral skull base presents technical challenges. The use of the eustachian tube as a landmark to identify the petrous internal carotid artery has recently been reported, and this study aims to define the anatomic relationship between the eustachian tube and its surrounding structures using cadaveric dissection and radiologic analysis. METHODS: To clarify the relationship of the eustachian tube with its surrounding structures, we performed endoscopic and microscopic dissection of 4 adult cadaveric heads and analyzed computed topography scans from 20 patients. RESULTS: The eustachian tube is divided into the osseous and cartilaginous parts. The cartilaginous part can be further subdivided into the posterolateral, middle, and anteromedial parts, based on its relationship to the skull base. The eustachian tube is closely related to the pterygoid process of the sphenoid bone, the foramen lacerum, and the petrosal apex and is directed away from the oblique sagittal plane almost parallel to the vidian canal at 12.2° ± 6.2° (mean ± standard deviation). The relationship between the course of the vidian canal and the eustachian tube can aid the estimation of the anatomic course of the horizontal segment of the petrous carotid artery. CONCLUSIONS: The eustachian tube is a useful landmark for predicting the course of the internal carotid artery when accessing the lateral skull base regions via an endonasal route. A profound understanding of the relationship between the eustachian tube and the surrounding skull base structures is important for endoscopic endonasal skull base surgeries.

Effect of treatment modality on in-hospital outcome in patients with subarachnoid hemorrhage: a nationwide study in Japan (J-ASPECT Study).

OBJECTIVE Although heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities. METHODS They analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis. RESULTS Patients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3-6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate. CONCLUSIONS Despite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.