Vascular stability of brain arteriovenous malformations after partial embolization.

INTRODUCTION: Brain arteriovenous malformation (bAVM) might have a higher risk of rupture after partial embolization, and previous studies have shown that some metrics of vascular stability are related to bAVM rupture risk. OBJECTIVE: To analyze vascular stability of bAVM in patients after partial embolization. METHODS: Twenty-four patients who underwent partial embolization were classified into the short-term, medium-term, and long-term groups, according to the time interval between partial embolization and surgery. The control group consisted of 9 bAVM patients who underwent surgery alone. Hemodynamic changes after partial embolization were measured by angiogram. The inflammatory infiltrates and cell-cell junctions were evaluated by MMP-9 and VE-cadherin. At the protein level, the proliferative and apoptotic events of bAVMs were analyzed by immunohistochemical staining of VEGFA, eNOS, and caspase-3. Finally, neovascularity and apoptotic cells were assessed by CD31 staining and TUNEL staining. RESULTS: Immediately after partial embolization, the blood flow velocity of most bAVMs increased. The quantity of MMP-9 in the medium-term group was the highest, and VE-cadherin in the medium-term group was the lowest. The expression levels of VEGFA, eNOS, and neovascularity were highest in the medium-term group. Similarly, the expression level of caspase-3 and the number of apoptotic cells were highest in the medium-term group. CONCLUSION: The biomarkers for bAVM vascular stability were most abnormal between 1 and 28 days after partial embolization.

Impact of qualifying artery on the efficacy of stenting plus medical therapy versus medical therapy alone in patients with symptomatic intracranial stenosis: a post-hoc analysis of the CASSISS trial.

BACKGROUND: A recent trial failed to show any benefit of stenting plus medical therapy over medical therapy alone in patients with symptomatic intracranial stenosis. We aimed to examine whether the symptomatic qualifying artery modifies the effect of stenting plus medical therapy. METHODS: This is a post-hoc analysis of the CASSISS trial that included patients with symptomatic intracranial stenosis, randomly assigned to undergo stenting plus medical therapy or medical therapy alone; 358/380 patients were included. Multivariable logistic regression analysis was used with an interaction term to estimate the altered treatment effect by the qualifying artery. The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The five secondary outcomes included stroke or death related to the qualifying artery territory at 2 and 3 years. RESULTS: No significant treatment allocation-by-stenosis site interaction was observed (Pinteraction=0.435). Compared with medical therapy alone, the adjusted ORs for stenting plus medical therapy were 2.73 (95% CI 0.42 to 17.65) for internal carotid artery stenosis, 1.20 (95% CI 0.29 to 4.99) for M1 stenosis, 0.23 (95% CI 0.02 to 2.31) for vertebral artery stenosis, and 1.33 (95% CI 0.34 to 5.28) for basilar artery stenosis. Of the five secondary outcomes, none showed a significant treatment allocation-by-stenosis site interaction including stroke in the qualifying artery territory at 2 years (Pinteraction=0.659) and 3 years (Pinteraction=0.493). CONCLUSIONS: Among patients with transient ischemic attacks or ischemic stroke due to severe intracranial atherosclerotic stenosis, there was no evidence that the symptomatic qualifying artery could determine the addition of stenting to medical therapy.

Comparison of drug-coated balloon with conventional balloon for angioplasty in symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Drug-coated balloon (DCB) angioplasty has been studied for reducing the occurrence of restenosis after treatment for intracranial atherosclerotic stenosis (ICAS), but no comparison has been published of the use of drug-coated and non-coated balloons in angioplasty for ICAS. We aim to compare the safety and efficacy of DCB angioplasty with conventional balloon (CB) angioplasty for the treatment of symptomatic ICAS. METHODS: One hundred cases with symptomatic ICAS treated with DCB (n=49) and CB (n=51) angioplasty were retrospectively analyzed. 1:1 propensity score matching (PSM) was completed to eliminate bias in the patients selected for further analysis. The periprocedural events and follow-up outcomes between the two groups were compared. RESULTS: There were 32 cases in each group after PSM. Technical success (<50% residual stenosis) was achieved in 30 cases (93.8%) in the DCB group and in 28 cases (87.5%) in the CB group. The rates of stroke or mortality within 30 days were 3.1% in the DCB group and 6.3% in the CB group (p=1). The incidence of restenosis in the DCB group (6.3%) was significantly lower than that in the CB group (31.3%) (p=0.01). CONCLUSIONS: Compared with CB angioplasty, DCB angioplasty can effectively reduce the incidence of restenosis. Further studies are needed to validate the role of DCB angioplasty in the management of symptomatic ICAS.

Safety and efficacy of the SeparGateTM balloon-guiding catheter in neurointerventional surgery: A prospective, multicenter, single-arm clinical trial.

Objective: To evaluate the safety and efficacy of the SeparGate™ balloon-guiding catheter (BGC) for blocking flow and delivering devices in neurointerventional surgery. Method: This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy. The primary endpoint was immediate procedural success rate in flow arrest, device delivery, and withdrawal. The efficacy endpoints were intraoperative product performance, including rigidity, smoothness, fracture resistance of the catheter wall, catheter push performance, compatibility and radiopaque display, integrity, adhesion thrombus after withdrawal and balloon rupture. The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration. Result: A total of 129 patients were included; of them, 128 were analyzed in the full analysis set (FAS) and per protocol set (PPS). Immediate procedural success was achieved in 97.7% of patients with FAS and PPS. The lower bound of the 95% confidence interval was 94.6%, higher than the preset efficacy margin of 94%. Device-related adverse events occurred in 2 (1.6%) cases. One was mild adverse event of vasospasm, which resolved spontaneously. The other was serious adverse event of dissection aggravation, which was treated with stenting angioplasty. No device defects were observed. Conclusion: In neurointerventional surgery, the SeparGate™ BGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.

Long Noncoding RNA DSCAM-AS1 Facilitates Proliferation and Migration of Hemangioma Endothelial Cells by Targeting miR-411-5p/TPD52 Axis.

Background: Diagnosed as a kind of vascular neoplasm of infancy, hemangioma (HA) occurs mainly due to the aberrant proliferation of endothelial cells. Existing evidence has manifested the close relationship of long noncoding RNAs (lncRNAs) with the pathogenesis of HA. Although lncRNA DSCAM antisense RNA 1 (DSCAM-AS1) has been revealed to be implicated in the progression of human diseases, the underlying mechanism DSCAM-AS1 exerts in HA formation is unclear. Aims: To figure out how DSCAM-AS1 may regulate the progression of human hemangioma endothelial cells (HemECs). Methods: DSCAM-AS1 expression was verified through RT-qPCR detection. Functional assays including EdU assay, colony formation assay, flow cytometry analysis, TUNEL assay, and transwell assay were applied to evaluate cell proliferation, apoptosis, and migration upon DSCAM-AS1 knockdown. Moreover, RNA pull-down assay, luciferase reporter assay, RIP assay, and other mechanism experiments were utilized for evaluating the correlation of DSCAM-AS1 and RNAs in HemECs. Results: DSCAM-AS1 knockdown inhibited proliferative capability and migratory capability of HemECs whereas expedited apoptosis. Molecular mechanism results testified DSCAM-AS1 could function as a ceRNA to bind miR-411-5p in HemECs. Besides, it was confirmed that tumor protein D52 (TPD52) served as a downstream target of miR-411-5p in HemECs. More importantly, related rescue assays uncovered that elevated expression of TPD52 or inhibited expression of miR-411-5p reversed the repressive progression of HemECs mediated by DSCAM-AS1 depletion. Conclusion: DSCAM-AS1 expedited HA progression via miR-411-5p/TPD52 pathway, which provided a novel therapeutic option for HA treatment.

LncRNA GAS5 promotes abdominal aortic aneurysm formation through regulating the miR-185-5p/ADCY7 axis.

One of the causes of abdominal aortic aneurysm (AAA) is the apoptosis of vascular smooth muscle cells. Many long noncoding RNA (lncRNAs) have been implicated in AAA formation. However, the mechanism of growth arrest-specific 5 (GAS5) in AAA formation is not yet clear. The expression levels of GAS5, microRNA-185-5p (miR-185-5p) and adenylate cyclase 7 (ADCY7) were determined by quantitative real-time PCR. Angiotensin II (ANGII) was used to induce AAA cell models. Cell viability was detected by MTT assay, and cell apoptosis was assessed by flow cytometry. Western blot analysis was used to test the protein expression levels. Besides, a dual-luciferase reporter assay was used to identify the mechanism of GAS5. GAS5 was upregulated in AAA tissues and ANGII-induced human aortic smooth muscle cells (HASMCs). GAS5 overexpression inhibited proliferation and promoted apoptosis and inflammatory response in ANGII-induced HASMCs, while its knockdown had the opposite effects. MiR-185-5p could be absorbed by GAS5, and its inhibitor could invert the effects of GAS5 silencing on proliferation, apoptosis and inflammatory response in ANGII-induced HASMCs. ADCY7 was a target of miR-185-5p. ADCY7 knockdown increased proliferation, while decreased apoptosis and inflammatory response in ANGII-induced HASMCs. Also, overexpressed ADCY7 reversed the effect of miR-185-5p overexpression on proliferation, apoptosis and inflammatory response in ANGII-induced HASMCs. GAS5 positively regulated the ADCY7 expression to inhibit the activity of the AKT signaling pathway by sponging miR-185-5p. LncRNA GAS5 contributed to AAA formation through regulating HASMCs proliferation, apoptosis and inflammatory response, which might provide new ideas for the treatment of AAA.

Predictors of futile recanalization in patients undergoing endovascular treatment in the DIRECT-MT trial.

BACKGROUND: Futile recanalization-when patients have a successful recanalization but fail to achieve a satisfactory functional outcome- is a common phenomenon of endovascular treatment of acute ischemic stroke (AIS). The present study aimed to identify the predictors of futile recanalization in AIS patients who received endovascular treatment. METHODS: This is a post-hoc analysis of the DIRECT-MT trial. Demographics, clinical characteristics, acute stroke workflow interval times, biochemical parameters, and imaging characteristics were compared between futile and meaningful recanalization groups. Multivariate analysis was performed to identify the predictors of futile recanalization. RESULTS: Futile recanalization was observed in 277 patients. In multivariable logistic regression analysis, older age (p<0.001), higher baseline systolic blood pressure (SBP) (p=0.032), incomplete reperfusion defined by extended Thrombolysis In Cerebral Infarction (eTICI) grades (p=0.020), and larger final infarct volume (FIV) (p<0.001) were independent predictors of futile recanalization. CONCLUSIONS: Old age, high baseline SBP, incomplete reperfusion defined by eTICI, and large FIV were independent predictors of futile recanalization after endovascular therapy for AIS.

Comparing the efficacy and safety of the Skyflow device with those of the Solitaire FR stent in patients with acute ischemic stroke: a prospective, multicenter, randomized, non-inferiority clinical trial.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS. METHODS: This study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation. RESULTS: A total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups. CONCLUSION: Endovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells.

Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (CDK1, CDC20, MCM5, MCM7, MCM4, CCNA2, AURKB, KIF2C, ESPL1, BUB1B) and DNA replication (POLE2, PLOE, CDC45, CDC6). Gene set enrichment analysis (GSEA) reveals that TNF-α/NF-κB and KRAS pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that TNF-α/NF-κB and KRAS pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers.

Prophylactic administration of tirofiban for preventing thromboembolic events in flow diversion treatment of intracranial aneurysms.

BACKGROUND: Flow diverter (FD) is widely used in the treatment of intracranial aneurysms. However, thromboembolic events (TEs) continue to be the major complications during the periprocedural phase. To evaluate the safety and efficacy of the prophylactic use of tirofiban, combined with the conventional dual antiplatelet therapy (DAT), as a new antiplatelet protocol in patients with intracranial aneurysms treated with FDs. METHODS: At least 3-5 days before the procedure, daily DAT were administrated to the patients. Tirofiban was administered as an intravenous bolus (5 µg/kg) over a 3 min period during or immediately after FD deployment, followed by a 0.05 µg/kg/min maintenance infusion for 24-48 hours. Periprocedural TEs and hemorrhagic events (HEs) were recorded. RESULTS: A total of 331 patients were included, including 229 (69.2%) who received tirofiban administration (tirofiban group) and 102 (30.8%) who received only DAT (non-tirofiban group). Periprocedural TEs occurred in 12 (3.6%) patients, including eight (7.8%) in the non-tirofiban group and four (1.7%) in the tirofiban group. In multivariate analysis, patients receiving tirofiban administration had significantly lower TEs as compared with those who received only DAT (P=0.004). Balloon angioplasty and longer procedure time (>137 min) were also risk factors for TEs. Also, no increase was observed in the rate of HEs related to tirofiban administration. CONCLUSIONS: The current study suggested that prophylactic administration of tirofiban combined with conventional oral DAT seems safe and efficient for preventing TEs during FD treatment of unruptured intracranial aneurysms. Balloon angioplasty and prolonged procedure are associated with a high risk of TEs.

Chinese Society of Interventional Radiology Expert Consensus on the prevention and control of COVID-19 in interventional radiology procedures (first edition).

The COVID-19 pandemic seriously threatens the lives of the general public and poses momentous challenges to all medical workers, including those engaged in interventional radiology, who play an important role in the diagnosis and treatment of various diseases. To further standardize the prevention and control of nosocomial infections and ensure the safety of doctors and patients, the Chinese Society of Interventional Radiology (CSIR) organized multidisciplinary experts in the field of interventional radiology in China to prepare an "Expert Consensus" elaborating and summarizing the protective strategies and suggestions for medical workers in the field of interventional radiology when they engage in interventional diagnosis and treatment activities against the background of novel coronavirus infection control. The aim is to provide a reference for interventional procedures in hospitals and other medical institutions at all levels in China and worldwide. The key points include the following: (I) non-emergency interventional diagnosis and treatment should be suspended while work is ongoing to prevent and control the spread of COVID-19; (II) protective measures should be taken according to the appropriate level designated for COVID-19 infection prevention and control; (III) patients should take measures to protect themselves when they want to see a doctor, including accessing outpatient services online and other relevant channels of consultation.

Safety and efficacy of the SeparGate™ balloon-guiding catheter in neurointerventional surgery: Study protocol of a prospective multicenter single-arm clinical trial.

BACKGROUND: The balloon-guiding catheter (BGC) reportedly reduces the number of retrievals and occurrence of distal emboli, achieving superior revascularization results and improved clinical outcomes in acute stroke. This study will aim to examine the efficacy and safety of the new SeparGate™ BGC. DESIGN: This prospective multicenter single-arm clinical trial will aim to include 128 patients who fulfill its inclusion and exclusion criteria. All patients will receive endovascular interventional therapy with BGC assistance. The primary endpoint will be the immediate surgical success rate, while the secondary endpoint will be product performance. The safety evaluation will include serious adverse events such as puncture site hematoma and bleeding, cerebral vasospasm, vessel dissection, vessel perforation, air embolism, thrombus (acute or subacute), vessel occlusion, distal embolization, infection, adverse reaction to antiplatelet and anticoagulant drugs, intracranial hemorrhage, stroke, death, and device defect. DISCUSSION: The prospective multicenter trial will provide safety and efficacy information for the SeparGate™ BGC. Its findings will provide a clinical reference for endovascular adjuvant therapy of cerebrovascular disease. TRIAL REGISTRATION: ChiCTR1800014459.

Intracranial Stenting as a Rescue Therapy for Acute Ischemic Stroke After Stentriever Thrombectomy Failure.

OBJECTIVE: To evaluate the efficacy and safety of intracranial stenting as a rescue therapy for acute ischemic stroke (AIS) after stentriever thrombectomy failure. METHODS: Patients who received intracranial stenting as a rescue therapy for AIS after failure of stent retrieval with or without concomitant treatment between January 2014 and December 2016 were retrospectively analyzed. Recanalization results and outcome at 3 months were assessed, and perioperative complications related to the procedure were recorded. RESULTS: A total of 193 patients with AIS received stent retriever thrombectomy. Initial successful recanalization with stent retriever was achieved in 125 patients. Among the 68 patients with stent retrieval failure, 47 patients received stent placement as rescue therapy, and successful recanalization was achieved in 38 patients. The rate of successful recanalization, favorable outcome at 90 days, mortality, and symptomatic intracerebral hemorrhage were comparable between the stenting group and no-stenting group; however, the time from groin puncture to recanalization was significantly longer in the stenting group (P = 0.03). Compared with anterior circulation stroke, the rate of stent placement was significantly greater (P = 0.041) and the intracerebral hemorrhage rate was lower in the patients with posterior circulation stroke who received stent placement. CONCLUSIONS: Intracranial stenting as a rescue therapy for AIS after failure of Solitaire retrieval stent is feasible and safe. AIS of posterior circulation showed greater intracranial stent placement than anterior circulation.

Safety and efficacy of a new prophylactic tirofiban protocol without oral intraoperative antiplatelet therapy for endovascular treatment of ruptured intracranial aneurysms.

BACKGROUND: Coil embolization of intracranial aneurysms is being increasingly used; however, thromboembolic events have become a major periprocedural complication. OBJECTIVE: To determine the safety and efficacy of prophylactic tirofiban in patients with ruptured intracranial aneurysms. METHODS: Tirofiban was administered as an intravenous bolus (8.0 µg/kg over 3 min) followed by a maintenance infusion (0.10 µg/kg/min) before stent deployment or after completion of single coiling. Dual oral antiplatelet therapy (loading doses) was overlapped with half the tirofiban dose 2 h before cessation of the tirofiban infusion. Cases of intracranial hemorrhage or thromboembolism were recorded. RESULTS: Tirofiban was prophylactically used in 221 patients, including 175 (79.19%) who underwent stent-assisted coiling and 46 (20.81%) who underwent single coiling, all in the setting of aneurysmal subarachnoid hemorrhage. Six (2.71%) cases of intracranial hemorrhage occurred, including four (1.81%) tirofiban-related cases and two (0.90%) antiplatelet therapy-related cases. There were two (0.90%) cases of fatal hemorrhage, one related to tirofiban and the other related to dual antiplatelet therapy. Thromboembolic events occurred in seven (3.17%) patients (6 stent-assisted embolization, 1 single coiling), of which one (0.45%) event occurred during stenting and six (2.72%) occurred during intravenous tirofiban maintenance. No thromboembolic events related to dual antiplatelet therapy were found. CONCLUSIONS: Tirofiban bolus over 3 min followed by maintenance infusion appears to be a safe and efficient prophylactic protocol for the endovascular treatment of ruptured intracranial aneurysms and may be an alternative to intraoperative oral antiplatelet therapy, especially in the case of stent-assisted embolization.

Perioperative complications of recanalization and stenting for symptomatic nonacute vertebrobasilar artery occlusion.

BACKGROUND: Endovascular recanalization and stenting has been used to treat patients with symptomatic nonacute intracranial vertebrobasilar artery occlusion (VBAO) refractory to aggressive medical treatment. This study was performed to analyze the perioperative complications of the procedures. METHODS: Between February 2010 and March 2012, 27 consecutive patients (24 men, 3 women; age: 57 ± 10 years) with symptomatic, nonacute intracranial VBAO including 12 basilar artery occlusions and 15 vertebral artery occlusions were collected and retrospectively analyzed. RESULTS: The median time between symptom onset and recanalization was 1.5 months (interquartile range [IQR]: 0.7-3.4) and between imaging-documented occlusion and recanalization was 9.5 days (IQR: 6-18 days). Recanalization was achieved in 96% of patients (26/27). Five (5/27; 19%) perioperative complications occurred. Two patients had dissections: 1 dissection resulted in termination of the procedure without successful recanalization, and the other was handled by the placement of 2 stents. There was 1 intraprocedural acute thrombosis that was successfully treated with balloon angioplasty. One patient experienced thrombus disruption and translocation during the procedure: thrombus was dislodged after disruption by the guidewire. There was 1 acute reocclusion after procedure: while recanalization was achieved again, there was no improvement in clinical outcome. CONCLUSIONS: This study revealed that recanalization and stenting for nonacute VBAO may be technically feasible but that it is accompanied by a high risk of complication. The causative factors for perioperative complications need future study.