Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Perioperative Low-Dose Aspirin Management for Planned Clipping Surgery: When, How Long, and With What Precautions?

BACKGROUND AND OBJECTIVE: Perioperative low-dose aspirin (ASA) management for open craniotomy surgery lacked information. We analyze to establish the perioperative ASA strategy to minimize both hemorrhagic and thromboembolic complications. METHODS: The investigators designed a multicenter retrospective study, which included patients scheduled to have clipping surgery for unruptured intracranial aneurysm. The incidence and risk factors were analyzed for postoperative hemorrhagic complications and major cardio- and cerebrovascular events (MACCEs) within 1 month postoperation. RESULTS: This study included 503 long-term ASA users of 3654 patients at three tertiary centers. The incidence of hemorrhagic complications and MACCEs was 7.4% (37/503) and 8.8% (44/503), respectively. Older age (>70 years, odds ratio [OR]: 2.928, 95% CI [1.337-6.416]), multiple aneurysms operation (OR: 2.201, 95% CI [1.017-4.765]), large aneurysm (>10 mm, OR: 4.483, 95% CI [1.485-13.533]), and ASA continuation (OR: 2.604, 95% CI [1.222-5.545]) were independent risk factors for postoperative hemorrhagic complications. Intracranial hemorrhage was the only type of hemorrhagic complication that increased in the ASA continuation group (10.6% vs 2.9%, P = .001). Between the ASA continuation and discontinuation groups, the overall incidence of MACCEs was not significantly different (log-rank P = .8). In the subgroup analysis, ASA discontinuation significantly increased the risk of MACCEs in the secondary prevention group (adjusted hazard ratio: 2.580, 95% CI [1.015-6.580]). CONCLUSION: ASA continuation increased the risk of postoperative intracranial hemorrhage. Simultaneously, ASA discontinuation was the major risk factor for postoperative MACCEs in the high-risk group. Without evidence of intracranial hemorrhage, early ASA resumption was indicated (a total cessation duration <7-10 days) in the secondary prevention group.

Prediction of cerebral hemorrhagic transformation after thrombectomy using a deep learning of dual-energy CT.

OBJECTIVES: To develop and validate a deep learning model for predicting hemorrhagic transformation after endovascular thrombectomy using dual-energy computed tomography (CT). MATERIALS AND METHODS: This was a retrospective study from a prospective registry of acute ischemic stroke. Patients admitted between May 2019 and February 2023 who underwent endovascular thrombectomy for acute anterior circulation occlusions were enrolled. Hemorrhagic transformation was defined using follow-up magnetic resonance imaging or CT. The deep learning model was developed using post-thrombectomy dual-energy CT to predict hemorrhagic transformation within 72 h. Temporal validation was performed with patients who were admitted after July 2022. The deep learning model's performance was compared with a logistic regression model developed from clinical variables using the area under the receiver operating characteristic curve (AUC). RESULTS: Total of 202 patients (mean age 71.4 years ± 14.5 [standard deviation], 92 men) were included, with 109 (54.0%) patients having hemorrhagic transformation. The deep learning model performed consistently well, showing an average AUC of 0.867 (95% confidence interval [CI], 0.815-0.902) upon five-fold cross validation and AUC of 0.911 (95% CI, 0.774-1.000) with the test dataset. The clinical variable model showed an AUC of 0.775 (95% CI, 0.709-0.842) on the training dataset (p < 0.01) and AUC of 0.634 (95% CI, 0.385-0.883) on the test dataset (p = 0.06). CONCLUSION: A deep learning model was developed and validated for prediction of hemorrhagic transformation after endovascular thrombectomy in patients with acute stroke using dual-energy computed tomography. CLINICAL RELEVANCE STATEMENT: This study demonstrates that a convolutional neural network (CNN) can be utilized on dual-energy computed tomography (DECT) for the accurate prediction of hemorrhagic transformation after thrombectomy. The CNN achieves high performance without the need for region of interest drawing. KEY POINTS: • Iodine leakage on dual-energy CT after thrombectomy may be from blood-brain barrier disruption. • A convolutional neural network on post-thrombectomy dual-energy CT enables individualized prediction of hemorrhagic transformation. • Iodine leakage is an important predictor of hemorrhagic transformation following thrombectomy for ischemic stroke.

Stereotactic radiosurgery for noncavernous sinus dural arteriovenous fistulas: treatment outcomes and their predictors.

OBJECTIVE: Stereotactic radiosurgery (SRS) has emerged as a safe and effective treatment modality for dural arteriovenous fistulas (dAVFs), particularly cavernous sinus (CS) dAVFs. However, the long-term outcomes of non-CS dAVFs are not well known. This study aimed to evaluate the efficacy and safety of SRS for non-CS dAVFs and to investigate the risk factors for incomplete obliteration. METHODS: Between 2007 and 2020, 65 non-CS dAVFs in 63 patients were treated using SRS at a single institution. Demographic characteristics, initial clinical presentations, clinical outcomes, and radiological findings were retrospectively reviewed. The procedure-related complications were assessed. Radiological outcomes were evaluated as complete obliteration, incomplete obliteration, and angiographic worsening, whereas clinical outcomes were evaluated for symptom recovery. RESULTS: At a median follow-up of 17 months, the overall complete obliteration rate was 63.1%, and the cumulative obliteration rates were 24.6%, 60.0%, 70.0%, and 74.3% at 12, 24, 36, and 48 months, respectively. Six patients underwent retreatment due to angiographic worsening; in 5 of these patients, recruitment of arterial feeders was newly observed in the adjacent sinus, which was not treated in the initial SRS. In the multivariate analysis, high-flow shunt and venous ectasia were associated with incomplete obliteration. No adverse events occurred after SRS. CONCLUSIONS: SRS for non-CS dAVFs is safe, and its efficacy is highly variable according to location. High-flow shunts may indicate greater radioresistance. In the retreated cases, new fistulas tended to be accompanied by sinus steno-occlusion and formed in the adjacent sinus segments.

Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm.

BACKGROUND: To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA). METHODS: Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs. RESULTS: In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping. CONCLUSIONS: Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters.

Endoscope-assisted microsurgical clipping and reduction of post-clipping cerebral infarction: historical comparison using diffusion-weighted images.

Endoscopic assistance for aneurysm clipping and its possible benefits have been suggested in previous studies, but its clinical significance has not been fully elucidated. This study aimed to present the efficacy of endoscopy-assisted clipping in reducing post-clipping cerebral infarction (PCI) and clinical outcomes via a historical comparison of patients in our institution from January 2020 to March 2022. A total of 348 patients were included, 189 of whom underwent endoscope-assisted clipping. The overall incidence of PCI was 10.9% (n = 38); it was 15.7% (n = 25) before applying endoscopic assistance and decreased to 6.9% (n = 13) after endoscope application (p = 0.010). The application of a temporary clip (odds ratio [OR]: 2.673, 95% confidence interval [CI]: 1.291-5.536), history of hypertension (OR: 2.176, 95% CI: 0.897-5.279), history of diabetes mellitus (OR: 2.530, 95% CI: 1.079-5.932), and current smoker (OR: 3.553, 95% CI: 1.288-9.802) were independent risk factors of PCI, whereas endoscopic assistance was an independent inverse risk factor (OR: 0.387, 95% CI: 0.182-0.823). Compared to the location of the unruptured intracranial aneurysms, internal carotid artery aneurysms showed a significant decrease in the incidence of PCI (5.8% vs. 22.9%, p = 0.019). In terms of clinical outcomes, PCI was a significant risk factor for longer admission duration, intensive care unit stay, and poor clinical outcomes. However, endoscopic assistance itself was not a significant risk factor for clinical outcomes on the 45-day modified Rankin Scale. In this study, we noted the clinical significance of endoscope-assisted clipping in preventing PCI. These findings could reduce the incidence of PCI and improve the understanding of its mechanisms of action. However, a larger and longer-term study is required to evaluate the benefits of endoscopy on clinical outcomes.

Subdural hygroma and hemorrhagic conversion after microsurgical clipping for unruptured intracranial aneurysm.

BACKGROUND: Chronic subdural hematoma (cSDH) is a unique hemorrhagic complication associated with microsurgical clipping. We aimed to investigate the risk factors of subdural hygroma (SDG) formation and its hemorrhagic conversion to cSDH. METHODS: We reviewed the medical records of 229 patients who underwent microsurgical clipping for unruptured intracranial aneurysms (UIA) from 2016 to 2019. Risk factors for SDG and cSDH formation were analyzed. RESULTS: Male sex, age ≥ 60 years, higher degree of arachnoid dissection, severe brain atrophy, and a large volume of subdural fluid collection (SFC) before discharge were independent risk factors for SDG formation. The risk factors for hemorrhagic conversion from SDG were continuous use or early resumption of antiplatelet drugs (odds ratio (OR): 15.367, 95% CI: 1.172-201.402) and a larger volume of SFC before discharge (OR: 0.932, 95% CI: 0.886-0.980). In the early resumption group, antiplatelet drug was resumed at a mean duration of 7.48 days postoperatively, and hemorrhagic conversion was detected earlier than that in the late resumption or no-use groups (4.09 vs. 7.18 weeks, P = 0.046). Following the receiver operating characteristic analysis, the SFC cutoff volume for hemorrhagic conversion was determined to be 23.55 mL. CONCLUSION: These findings can assist clinicians in identifying patients at a high risk of SDG and cSDH formation. Antiplatelet resumption and its timing should be determined with consideration of the risk of cSDH formation as well as individual medical conditions.

Added Predictive Values of Proton Density Magnetic Resonance Imaging on Posterior Communicating Artery Aneurysms and Surrounding Soft Tissues with Simple Classification.

OBJECTIVE: Deciphering the anatomy of posterior communicating artery (PCoA) aneurysms in relation to surrounding structures is essential to determine adjuvant surgical procedures. However, it is difficult to predict surgical structures through preoperative imaging studies. We aimed to present anatomical structures using preoperative high-resolution three-dimensional proton densityweighted turbo spin-echo magnetic resonance (PDMR) imaging with simple classification. METHODS: From January 2020 to April 2022, 30 patients underwent PDMR before microsurgical clipping for unruptured PCoA aneurysms in a single tertiary institute. We retrospectively reviewed the radiographic images and operative data of these patients. The structural relationship described by PDMR and intraoperative findings were compared. Subsequently, we classified aneurysms into two groups and analyzed the rate of adjuvant surgical procedures and contact with the surrounding structures. RESULTS: Correlations between preoperative PDMR predictions and actual intraoperative findings for PCoA aneurysm contact to the oculomotor nerve, temporal uncus, and anterior petroclinoid fold (APCF) reported a diagnostic accuracy of 0.90, 0.87, and 0.90, respectively. In 12 patients (40.0%), an aneurysm dome was located on the plane of the oculomotor triangle and was classified as the infratentorial type. Compared to the supratentorial type PCoA aneurysm, adjuvant procedures were required more frequently (66.7% vs. 22.2%, p=0.024) for infratentorial type PCoA aneurysm clipping. CONCLUSION: Preoperative PCoA aneurysm categorization using PDMR can be helpful for predicting surgical complexity and planning of microsurgical clipping.

Comparison of Single-Session, Neoadjuvant, and Adjuvant Embolization Gamma Knife Radiosurgery for Arteriovenous Malformation.

BACKGROUND: The purpose of intracranial arteriovenous malformations (AVMs) treatment is to prevent bleeding or subsequent hemorrhage with complete obliteration. For large, difficult-to-treat AVMs, multimodal approaches including surgery, endovascular embolization, and gamma knife radiosurgery (GKRS) are frequently used. OBJECTIVE: To analyze the outcomes of AVMs treated with single-session, neoadjuvant, and adjuvant embolization GKRS. METHODS: We retrospectively reviewed a database of 453 patients with AVMs who underwent GKRS between January 2007 and December 2017 at our facility. The obliteration rate, incidence of latent period bleeding, cyst formation, and radiation-induced changes were compared among the 3 groups, neoadjuvant-embolized, adjuvant-embolized, nonembolized group. In addition, the variables predicting AVM obliteration and complications were investigated. RESULTS: A total of 228 patients were enrolled in this study. The neoadjuvant-embolized, adjuvant-embolized, and nonembolized groups comprised 29 (12.7%), 19 (8.3%), and 180 (78.9%) patients, respectively. Significant differences were detected among the 3 groups in the history of previous hemorrhage and the presence of aneurysms ( P < .0001). Multivariate Cox regression analyses revealed a significant inverse correlation between neoadjuvant embolization and obliteration occurring 36 months after GKRS (hazard ratio, 0.326; P = .006). CONCLUSION: GKRS with either neoadjuvant or adjuvant embolization is a beneficial approach for the treatment of AVMs with highly complex angioarchitectures that are at risk for hemorrhage during the latency period. Embolization before GKRS may be a negative predictive factor for late-stage obliteration (>36 months). To confirm our conclusions, further studies involving a larger number of patients and continuous follow-up are necessary.

Photoresponsive Hydrogels for Studying Mechanotransduction of Cells.

Hydrogels are important platform materials for in vitro cellular studies. Mechanistic studies on durotaxis, the directional movement of a cell affected by a spatial gradient of stiffness of the underlying substrate, requires materials such as polyacrylamide, polyethylene glycol, or PDMS, in which the stiffness can be controlled in a spatiotemporal manner. Here, we describe the synthesis of an o-nitrobenzyl-based photocleavable cross-linker and its incorporation into a polyacrylamide hydrogel to render it photoresponsive. Precise control over the physical properties of the gel allows observation of glioblastoma durotaxis under surface stiffness conditions relevant to the actual brain environment.

Efficacy and safety of stereotactic radiosurgery versus endovascular treatment for symptomatic cavernous sinus dural arteriovenous fistula without ophthalmological emergency: a single-center 10-year experience.

OBJECTIVE: Stereotactic radiosurgery (SRS) is emerging as a treatment option for cavernous sinus dural arteriovenous fistula (CS dAVF); it is less invasive and has a lower complication rate than conventional surgeries. However, little is known regarding the advantages and limitations of SRS compared to those of endovascular treatment (EVT). The aim of this study was to compare the efficacy and safety between EVT and SRS for treatment of CS dAVF. METHODS: Between January 2011 and April 2021, a total of 86 consecutive patients diagnosed with CS dAVF were treated with EVT or SRS. Among them, 8 patients with ophthalmological emergency and 8 without follow-up data at ≥ 12 months were excluded. During the same period, no neurological deficit due to intracranial hemorrhage or seizure was noted in any of the patients. Ultimately, 70 patients (EVT 33, SRS 37) were included in this study. Demographic characteristics, initial clinical presentations, clinical outcomes, and radiological findings were retrospectively reviewed and compared. Procedure-related complications were also assessed after the treatments. RESULTS: The patients' baseline characteristics (except conjunctival symptoms) and angiographic features of CS dAVF were not significantly different between the EVT and SRS groups. Conjunctival symptoms were more frequently noted in the EVT than in the SRS group (69.7% vs 40.5%, p = 0.015). After EVT, initial complete obliteration was achieved in 20 cases (60.6%). Complete obliteration was achieved at 6 months in 86.4% of cases with EVT and in 77.8% of those treated with SRS (p = 0.507), and at 12 months in 86.4% cases with EVT and in 94.4% of those treated with SRS (p = 0.357). Worsening of symptoms developed at 1 month in 24.2% of cases with EVT and in 5.4% of those treated with SRS (p = 0.038); at 6 months in 22.6% of cases with EVT and in 10.8% of those treated with SRS; and at 12 months in 30.0% of cases with EVT and in 13.5% of those treated with SRS (p = 0.099). The angioarchitecture of CS dAVF did not affect angiographic obliteration after SRS. Procedure-related morbidity and mortality occurred more frequently in the EVT than in the SRS group (27.3% vs 8.1%, p = 0.034). CONCLUSIONS: Both EVT and SRS were effective for the treatment of CS dAVF without ophthalmological emergency. However, procedure-related morbidity and mortality was less frequent in SRS than in EVT, and consequently SRS may be more advantageous in terms of safety.

Alterations of vital signs as prognostic factors after intraprocedural rupture of intracranial aneurysms during endovascular treatment.

OBJECTIVE: To report our experience with intraprocedural rupture (IPR) of intracranial aneurysms during endovascular treatment and evaluate alterations in vital signs as independent prognostic factors to predict the outcomes of IPR. METHODS: Between January 2008 and August 2021, 34 patients (8 ruptured and 26 unruptured) were confirmed to have IPR based on our dataset with 3178 endovascular coiling procedures. The patients who underwent additional surgeries related to IPR were classified as the OP group (n=9), while those who did not receive additional surgeries were classified as the non-OP group (n=25). Vital signs were recorded during the procedure by anesthesiologists and analyzed. RESULTS: Of the 34 patients included in this study, eight initially presented with subarachnoid hemorrhage due to a ruptured aneurysm. The clinical outcomes at discharge were significantly different between the two groups (p=0.046). In the OP group, five patients showed favorable outcomes at discharge, while four showed unfavorable outcomes. In the non-OP group, 23 patients showed favorable outcomes at discharge while two patients showed unfavorable outcomes. Maximal (MAX) systolic blood pressure (SBP) (odds ratio [OR] 1.520, 95% confidence interval [CI] 1.084-2.110; p=0.037) and higher differential value MAX-median blood pressure (MBP) (OR 1.322, 95% CI 1.029-1.607; p=0.044) remained independent risk factors for poor prognosis after IPR on multivariate logistic regression analysis. CONCLUSIONS: The MAX SBP and the difference between the maximal and baseline values of MBP are key factors in predicting the prognosis of patients after IPR, as well as providing useful information for predicting the outcome. Further research is required to confirm the relationship between naive pressure and prognosis.

Risk factors for recanalization of basilar tip aneurysm after endovascular treatment: a retrospective cohort study.

OBJECTIVES: Endovascular treatment (EVT) of basilar tip aneurysms (BTAs) is arduous because of the lesions' angioarchitecture and the relatively high recanalization rate after EVT. In this study, we aimed to report the clinical characteristics of BTAs and evaluate the incidence of and risk factors for recanalization. METHODS: One hundred twenty-five patients with BTAs (11 ruptured, 114 unruptured) treated with EVT between 2009 and 2019 at one institution were retrospectively reviewed. Among them, 113 patients were included in statistical analyses. The anatomical parameters of the aneurysms and clinical data were analyzed. Univariate (chi-square test and t-test) and multivariate (multiple logistic regression) analyses were performed to identify risk factors for recanalization. RESULTS:         Recanalization of the BTA occurred in 15 patients (13.3%). One patient (0.9%) was retreated endovascularly. The mean follow-up duration was 49.8 months. Neck size, posterior cerebral artery (PCA) angle, maximum diameter, and the rupture rate differed significantly between the recanalization and non-recanalization groups (P=.007, P<.001, P=.006, and P=.048, respectively). The maximum diameter (odds ratio, 1.483 per mm; 95% confidence interval, 1.145-1.919; P=.003) and PCA angle (odds ratio, 1.020 per degree; 95% confidence interval, 1.001-1.039; P=.036) were independently associated with recanalization. CONCLUSIONS: Of all investigated BTAs, 96.8% were wide-neck aneurysms. The recanalization rate of BTAs after EVT was 13.3%. The PCA angle and maximal aneurysmal diameter were independently associated with recanalization; no associations were observed regarding vertebral artery dominance or modality of treatment. As such, BTA patients with wide PCA angles should be carefully monitored over time.

Angioarchitectural Analysis of Arteriovenous Shunts in Dural Arteriovenous Fistulas and Its Clinical Implications.

BACKGROUND: Detailed understanding of the angioarchitecture of arteriovenous shunts in dural arteriovenous fistulas (DAVFs) is essential when planning endovascular treatment. OBJECTIVE: To analyze shunt patterns and their clinical implications in transverse-sigmoid sinus and superior sagittal sinus DAVFs. METHODS: A total of 48 DAVFs treated with endovascular embolization between January 2010 and June 2021 were investigated. The preprocedural and intraprocedural digital subtraction angiograms were examined to characterize the shunt patterns of DAVFs in terms of anatomic relations to the sinuses and cortical veins. Treatment characteristics and outcomes were evaluated. RESULTS: The shunt patterns were categorized into 4 types: the direct sinus fistula (n = 8/48, 16.7%), compartmental sinus channel (n = 14/48, 29.1%), mural channel (n = 13/48, 27.1%), and bridging vein shunt (n = 13/48, 27.1%). Mural channel lesions revealed direct (n = 4/13, 30.8%) and indirect (n = 6/13, 46.2%) cortical venous connections. Multiple shunt types were seen in 7 patients. Overall, complete or near-complete occlusion was achieved in 43 patients (89.6%) after the final embolization. Patients with mural channels received the most embolization sessions (1.4 sessions per patient). Procedural venous drainage-related complications occurred in patients with multiple shunt types including mural channel shunts (n = 3). All bridging vein shunts were completely occluded during a single transarterial embolization session. CONCLUSION: The 4 shunt patterns of DAVFs demonstrate distinct characteristics for the fistula, sinus and cortical vein connection. Meticulous analysis of the angioarchitectural characteristics and clinical implications is warranted for safe and effective treatment.

Directed cell migration towards softer environments.

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery.

Optimal Duration of Dual Antiplatelet Therapy after Stent- Assisted Coil Embolization of Unruptured Intracranial Aneurysms : A Prospective Randomized Multicenter Trial.

OBJECTIVE: Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). METHODS: This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

Incidence rate and predictors of recurrent aneurysms after clipping: long-term follow-up study of survivors of subarachnoid hemorrhage.

Recurrent aneurysms are a major cause of re-aneurysmal subarachnoid hemorrhage (aSAH), but information on long-term clip durability and predictors is insufficient. This study aimed to present the incidence rate of > 10 years and investigate predictors of a recurrent aneurysm in aSAH survivors. We included 1601 patients admitted with aSAH and treated by microsurgical clipping between January 1993 and May 2010. Of these patients, 435 aSAH survivors were included in this study (27.2%). The total follow-up time was 5680.9 patient-years, and the overall incidence rate was 0.77% per patient-year. The cumulative probability of recurrence without residua and regrowth of the neck remnant was 0.7% and 13.9% at 10 years, respectively. Neck remnant (hazard ratio [HR], 10.311; 95% confidence interval [CI], 5.233-20.313) and alcohol consumption over the moderate amount (HR, 3.166; 95% CI, 1.313-7.637) were independent risk factors of recurrent aneurysm. Current smoking and multiplicity at initial aSAH presentation were significant factors in a univariate analysis. Furthermore, de novo intracranial aneurysms (DNIAs) were more common in the recurrent group than in the non-recurrent group (40.9% vs. 11.5%, P < 0.001). In the present study, we noted the long-term clip durability and predictor of recurrence after microsurgical clipping. These findings can assist clinicians in identifying patients at a high risk of recurrent aneurysm and recommending selective long-term surveillance after microsurgical clipping.

Adsorption mechanisms on perfluorooctanoic acid by FeCl3 modified granular activated carbon in aqueous solutions.

Perfluorooctanoic acid (PFOA) is an emerging organic pollutant that is persistent in the environmental, and has been detected in humans, and wildlife. Several technologies, such as activated carbon (AC) adsorption have been used to remove PFOA from water. In this study, Fe-impregnation with/without post-thermal treatment of AC was applied to improve the adsorption of PFOA. The adsorption mechanisms were evaluated using three kinetic models: pseudo-first-order model, pseudo-second-order model, and intra-particle diffusion models. Interpretation of experimental results with the kinetic models revealed that chemical interactions, such as electrostatic attraction or complexation were suggested as the adsorption mechanisms along with physical adsorption. Two isotherm models demonstrated that the modified ACs (171.0-189.9 mg g-1) had increases in adsorption capacities than the unmodified AC (164.9 mg g-1), which indicated that modification improved the maximum achievable surface concentrations and adsorption affinity to some extent. The evenly distributed iron content on the modified ACs was visualized using an energy dispersive X-ray spectroscopy. The Fe-impregnated AC showed a reduction in the specific surface area and total pore volume; however, post-thermal treatment largely recovered the pore structures. The isotherms normalized by the accessible surface area revealed the importance of the Fe-impregnated surfaces on PFOA adsorption. Comparable pH values of the point of zero charge and chemical compositions of the ACs implied that an increase in Fe-impregnated surface was crucial to improve PFOA adsorption. Thus, substantial enhancement of PFOA removal can be achieved by implementing a proper strategy for AC modification, especially using Fe-impregnation.

Endovascular treatment for large (> 10 mm) basilar tip aneurysms: a retrospective case series.

PURPOSE: To report the long-term clinical and angiographic outcomes of the endovascular treatment of large/giant basilar tip aneurysms (BTAs) in our institutions. METHODS: We retrospectively reviewed cases of BTA larger than 10 mm that received endovascular treatment between January 2009 and December 2019. Data on the demographic and clinical characteristics and radiologic severity were obtained from the patients' medical records. The collected clinical follow-up data included neurological evaluation. Magnetic resonance angiography (MRA) was performed 6 to 12 months after the procedure, followed by once every 1 to 2 years as needed. RESULTS: A total of 12 patients with BTA were included in this study. The median age was 60.08 years (27-80 years), and the mean clinical follow-up was 66.78 months (19.00-142.87 months). Almost half of the patients presented with unruptured BTAs (58.33%, n = 7). The median maximum aneurysm diameter was 13.00 mm (10.46-20.90 mm) and the mean neck size was 8.34 mm (4.82-13.04 mm). A Modified Raymond Roy Classification (MRRC1) of 1 or 2 was observed in 66.67% of the patients (n = 8) immediately after the first procedure. Procedural morbidity and mortality were 33.33% and 8.33%, respectively. Major recanalization occurred in two patients, one of whom underwent additional coiling with the other being merely observed due to older age. CONCLUSION: It is very difficult to cure a large BTA completely at once and recanalization occurred often after endovascular treatment. Conducting long-term follow-up studies at short intervals is warranted, as well as improving existing treatment methods and developing new approaches.

Flow diverter for the treatment of large (> 10 mm) vertebral artery dissecting aneurysms.

OBJECTIVE: To evaluate the outcomes of flow-diverting device (FDD) treatment for large vertebral artery dissecting aneurysms (VADAs). METHODS: This retrospective study evaluated 12 patients with 12 VADAs who were treated using FDD between 2013 and 2020. Clinical and radiographic data, including procedure-related complications and clinical outcomes assessed using the modified Rankin Scale (mRS) at the time of the last follow-up, were collected and reviewed. RESULTS: All 12 patients had unruptured aneurysms. There were 3 (25%) female and 9 (75%) male patients, and the mean patient age was 54.6 years. The mean size of the aneurysm was 15.9 ± 4.8 mm. The mean follow-up duration was 15.8 months. Single FDD without additional coils was used in all patients. One patient underwent second-line treatment with FDD for recurrence of large VADA after stent-assisted coiling. Immediate follow-up angiography after placement of the FDD demonstrated intra-aneurysmal contrast stasis. There were 2 (17%) patients who had peri-procedural stroke. Angiography at the 6-month follow-up in 10 patients showed favorable occlusion (OKM grade C3 + D). A total of 11 (92%) patients had good clinical outcome (modified Rankin Scale ≤ 2) at the last follow-up. No re-treatment or delayed aneurysm rupture occurred during the follow-up period. CONCLUSIONS: Reconstructive technique with FDD is a feasible and effective modality for the treatment of large VADAs, showing favorable occlusion rate and clinical outcome.