Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.

BACKGROUND: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. METHODS: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. FINDINGS: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. INTERPRETATION: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. FUNDING: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

Rescue Strategy for Hemorrhagic Complication During Mechanical Thrombectomy and the Clinical Outcome.

PURPOSE: Hemorrhagic complications occasionally occur during mechanical thrombectomy and may lead to catastrophic outcomes. Therefore, remedial strategies require careful investigation. Herein, we aimed to evaluate a cohort of patients who experienced hemorrhage during endovascular procedures, the rescue methods used, and outcomes observed. METHOD: This prospective study included patients who had hemorrhagic complications observed on digital subtraction angiography (DSA) during mechanical thrombectomy, between October 2017 and October 2022, at a high-volume stroke center. Functional outcomes were assessed using the modified Rankin scale (mRS) score at a 90-day follow-up. The primary outcomes were favorable outcomes (mRS score: 0-2 points) and mortality rates. The secondary outcomes were rescue therapy success rates, according to extravasation observed on the final DSA, recanalization status, and causes of hemorrhage. RESULTS: From October 2017 to October 2022, 1537 patients with stroke received emergency endovascular therapy, and 1147 patients completed a 90-day follow-up. Hemorrhage was observed in 33 (2.1%) patients in the process of endovascular interventions. Eighteen (54.5%) cases of hemorrhage were caused by microwire or microcatheter perforation. Mechanical stretching of the vessel during stent retriever withdrawal resulted in 8 (24.2%) cases of hemorrhage. Nine (27.3%) instances of hemorrhage stopped after the reversal of heparin administration and introduction of blood pressure control measures. Further endovascular rescue treatment was performed in 11 patients. Intracranial inflation of the balloon for tamponade stopped 10 hemorrhages, and 1 patient underwent additional coil embolization. Fifteen (45.5%) patients died within 90 days after the procedure. Three (9.1%) patients recovered functional independence (mRS score: 0-2 points) within 90 days. CONCLUSION: Hemorrhage during mechanical thrombectomy is a rare but severe complication of acute ischemic stroke with high mortality and disability rates. Intracranial inflation of a balloon for tamponade can effectively stop extravasation. CLINICAL IMPACT: This paper described haemorrhagic events characterised by contrast extravasation in the procedure of mechanical thrombectomy due to various causes. Although this complication is rare, patients showed a high mortality and disability rate. There are limited reports available. We found self-limiting haemorrhage had a rather benign prognosis and balloon tamponade could effectively stop the extravasation and might reduce the death rate within 90d. The methods we adopted could be applied in the clinical practice and help neuro-interventionist cope with this complication more promptly and effectively.

Which glucose parameter best predicts poor outcome after mechanical thrombectomy for acute large vessel occlusion stroke?

BACKGROUND: Hyperglycaemia is related to adverse outcomes in patients with acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT). AIMS: To compare the predictive ability of admission blood glucose (ABG), fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) in patients with acute large vessel occlusion (ALVO) stroke undergoing MT. METHODS: The study retrospectively analysed the data of 329 consecutive acute stroke patients treated with MT. Multivariate logistic regression analysis was performed to investigate the predictors of poor functional outcome. Receiver operating characteristic (ROC) analysis was performed to identify the predictive ability of ABG, FBG and HbA1c for poor functional independence in patients with ALVO stroke undergoing MT. In addition, subgroup analyses were performed for both diabetic and non-diabetic patients. RESULTS: Multiple logistic regression analysis demonstrated that ABG and FBG were independent predictors of 3-month poor functional outcome; however, HbA1c could not predict poor functional outcome. ROC analysis showed that FBG has a higher predictive ability than ABG (areas under the ROC curve (AUC): 0.689 vs 0.624; P = 0.037) and HbA1c (AUC: 0.689 vs 0.541; P < 0.001) for poor function outcome. CONCLUSIONS: ABG and FBG are independent predictors of poor functional outcome in patients with AIS undergoing MT, and FBG has a higher predictive ability than ABG and HbA1c.

Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke: The RESCUE BT Randomized Clinical Trial.

Importance: Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022. Interventions: Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 948 patients randomized (mean age, 67 years; 391 [41.2%] women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% [95% CI, -0.2% to 6.8%]). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.

Experiment Study for Wrist-Wearable Electro-Tactile Display.

Tactile sensation is a promising information display channel for human beings that involves supplementing or replacing degraded visual or auditory channels. In this paper, a wrist-wearable tactile rendering system based on electro-tactile stimulation is designed for information expression, where a square array with 8 × 8 spherical electrodes is used as the touch panel. To verify and improve this touch-based information display method, the optimal mode for stimulus signals was firstly investigated through comparison experiments, which show that sequential stimuli with consecutive-electrode-in-active mode have a better performance than those with single-electrode-in-active mode. Then, simple Chinese and English characters and 26 English characters' recognition experiments were carried out and the proposed method was verified with an average recognition rate of 95% and 82%, respectively. This wrist-wearable tactile display system would be a new and promising medium for communication and could be of great value for visually impaired people.

Anatomical distribution of lower-extremity deep venous thrombosis in patients with acute stroke.

OBJECTIVE: Post-stroke paralysis is a common contributor to deep vein thrombosis (DVT) of the lower extremities, but little is known about its epidemiology and anatomy. This prospective study aimed to investigate the clinical incidence and anatomical distribution of lower-extremity DVT in acute stroke. PATIENTS AND METHODS: A total of 679 patients diagnosed with acute stroke (ischemic stroke, n = 507; hemorrhagic stroke, n = 172) were enrolled. Lower-extremity DVT was evaluated using vascular ultrasonography, and classified into three subtypes: central type, peripheral type and mixed type. Then, the incidence and anatomical distribution of DVT were analyzed. RESULTS: For patients with ischemic stroke, a total of 107 patients (21.1%) were affected by DVT, and 119 extremities were found with DVT, which included 114 extremities with peripheral-type DVT and five extremities with mixed-type DVT. For patients with hemorrhagic stroke, a total of 49 patients (28.5%) were affected by DVT, and 55 extremities were found with DVT, which included 51 extremities with peripheral-type DVT and four extremities with mixed-type DVT. The incidence of DVT was significantly higher in patients with hemorrhagic stroke than in patients with ischemic stroke (P < 0.05). Intermuscular veins were the most commonly affected (96.6%), followed by peroneal veins (15.5%), posterior tibial veins (9.2%), popliteal veins (4.0%), and femoral veins (4.0%). There was no significant difference in the anatomical distribution of DVT between ischemic and hemorrhagic stroke (P > 0.05). CONCLUSION: DVT is a common complication of acute stroke, and hemorrhagic stroke is associated with a higher incidence of DVT. The anatomical distribution of DVT revealed no heterogeneity between ischemic and hemorrhagic stroke, and isolated DVT in intermuscular veins were the most common.

The Therapeutic Effects of Endovascular Therapy with mTICI2b and 3 Recanalization for Acute Anterior Circulation Stroke Patients.

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction (mTICI)2b/3 has been considered the criterion for successful reperfusion in endovascular treatment. This study aimed to compare the therapeutic safety and efficacy of mTICI2b and mTICI3 recanalization, and to analyze the factors related to outcomes in everyday clinical practice. MATERIALS AND METHODS: This is a single-center retrospective analysis of 224 patients who underwent successful thrombectomy (achieving a mTICI score ≥2b). The primary outcomes included a modified Rankin score (mRS) of 0-2 at 90-day, mortality, and symptomatic intracranial hemorrhage. RESULTS: A total of 111 patients achieved mTICI2b status (49.6%), and 113 achieved mTICI3 status (50.4%). The comparison between mTICI2b and 3 reperfusions showed no differences in short-term outcomes, 90-day mRS, complications, and mortality. There was a trend toward more passes in mTICI2b patients, although the difference was not significant. The univariate analysis showed that poor outcomes after endovascular treatment were associated with older age, previous history of coronary heart disease, atrial fibrillation, diabetes, tandem occlusions, high National Institutes of Health Stroke Scale (NIHSS) score on admission, and general anesthesia. A previous history of coronary heart disease, a high NIHSS score on admission, and the use of general anesthesia were independent factors that affected the therapeutic effects. CONCLUSION: The superiority (efficacy and safety) of mTICI3 reperfusion was not significant compared with that of mTICI2b reperfusion. Prolonged efforts to achieve mTICI3 after achieving mTICI2b should be considered prudently for those with difficulty achieving 100% reperfusion.

Current Understanding of Dolichoarteriopathies of the Internal Carotid Artery: A Review.

Dolichoarteriopathies of the internal carotid artery (DICAs) are not uncommon, and although several studies have investigated DICAs, several questions regarding the etiology and best management course for DICAs remain unanswered. It is also difficult to correlate the occurrence of DICAs with the onset of clinical symptoms. Therefore, we surveyed the literature in PubMed and performed a review of DICAs to offer a comprehensive picture of our understanding of DICAs. We found that DICAs can be classified into three types, specifically tortuous, coiling and kinking, and are not associated with atherosclerotic risk factors. Cerebral hemodynamic changes are mainly associated with the degree of bending of DICAs. DICAs can result in symptoms of the brain and eyes due to insufficient blood supply and can co-occur with a pulsatile cervical mass, a pharyngeal bulge and pulsation. The diagnostic tools for the assessment of DICAs include Doppler ultrasonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), and although DSA remains the gold standard, Doppler ultrasonography is a convenient method that provides useful data for the morphological evaluation of DICAs. CTA and MRA are efficient methods for detecting the morphology of the cervical segment of DICAs. Some DICAs should be treated surgically based on certain indications, and several methods, including correcting the bending or shortening of DICAs, have been developed for the treatment of DICAs. The appropriate treatment of DICAs results in good outcomes and is associated with low morbidity and mortality rates. However, despite the success of surgical reconstruction, an appropriate therapeutic treatment remains a subject of numerous debates due to the lack of multicentric, randomized, prospective studies.

Intra-arterial tenecteplase during thrombectomy for acute stroke (BRETIS-TNK II): rationale and design.

BACKGROUND: Our recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS) patients with large-vessel occlusion (LVO). AIMS: To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom onset. SAMPLE SIZE ESTIMATES: A maximum of 380 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, baseline systolic blood pressure, prestroke modified Rankin Scale (mRS), baseline National Institute of Health stroke scale, baseline ASPECTS, time from onset to groin puncture, intravenous thrombolysis before EVT, stroke territory and stroke aetiology. DESIGN: Intra-arterial TNK during thrombectomy for acute stroke (BRETIS-TNK II) study is a prospective, randomised, adaptive enrichment, open-label, blinded end point, multicentre study. Eligible AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:1. The experimental group will be treated with intra-arterial infusion of TNK during EVT. The control group will be treated with standard EVT. OUTCOME: The primary end point is a favourable outcome, defined as an mRS score of 0-2 at 90 days. The primary safety end point is symptomatic intracranial haemorrhage within 48 hours, which is defined as an increase in the National Institutes of Health Stroke Scale score of ≥4 points as a result of the intracranial haemorrhage. CONCLUSIONS: The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

Balloon angiopLasty for intracranial Atherosclerotic minor Stroke/TIA (BLAST): study protocol for a multicenter prospective cohort study.

Rationale/Aim: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke in Asia and is significantly associated with stroke recurrence. The Balloon angiopLasty for intracranial Atherosclerotic minor Stroke/TIA (BLAST) study aims to evaluate the safety and effectiveness of early submaximal balloon angioplasty (SBA) combined with standard medical therapy vs. standard medical therapy alone in patients with minor stroke or transient ischemic attack (TIA) due to ICAS. Methods: The BLAST study is a multicenter prospective cohort study which will enroll patients with minor stroke or TIA due to symptomatic ICAS within 1 week of symptom onset from 20 centers in China. Eligible patients will receive either SBA with standard medical therapy or standard medical therapy alone based on the decision of the patient or legal representative. Participants will be followed up for 1 year. Study outcomes: The primary outcome is a composite of stroke or death within 30 days or ischemic stroke in the culprit artery territory from 30 days to 1 year. Secondary outcomes include stroke or death within 30 days, ischemic stroke in the culprit artery territory from 30 days to 1 year, restenosis rate of the culprit artery at 1 year, and neurological improvement at 90 days (assessed by mRS score). Safety outcomes include intracranial hemorrhage within 30 days and endovascular complications. Sample size estimate: According to previous studies, the incidence of the composite clinical outcomes is 15% in the group receiving medical therapy alone. We assumed the incidence would decrease to 5% in the SBA combined with the medical therapy group. The target sample size is 416 patients (208 per group), with 90% power and 5% type I error, allowing for a 10% loss to follow-up. Implications: The BLAST study will provide evidence regarding whether early SBA can reduce stroke recurrence and mortality in patients with minor stroke/TIA due to ICAS compared with medical therapy alone.Clinical trial registration:Clinicaltrials.gov, NCT06014723.

Revascularization of vertebrobasilar artery occlusion at the chronic stage.

We describe a patient who underwent intracranial angioplasty and Solitaire stent placement for recanalization of a vertebrobasilar artery occlusion 2 months after symptom onset. Computed tomography angiography and digital subtraction angiography showed that both vertebral arteries and the proximal basilar artery were occluded. Balloon angioplasty was performed on a segment of the occluded left vertebral artery and basilar artery, followed by successful detachment of one Solitaire stent. Repeat angiography showed near normal patency of the left vertebrobasilar artery. The patient`s symptoms improved significantly, and postoperative transcranial Doppler sonography 3 months later showed no evidence of in-stent restenosis.

Comprehensive classifications for the endovascular recanalization of vertebral artery stump syndrome.

Background: and purpose: To share our single-center vertebral artery stump syndrome (VASS) treatment experience and assess the role of comprehensive classification based on anatomic development, proximal conditions, and distal conditions (PAD). Materials and methods: Data were retrospectively collected from patients who underwent endovascular thrombectomy (EVT) at the Stroke Center of the First Hospital of Jilin University between January 2016 and December 2021. Among patients with acute ischemic stroke in the posterior circulation, those with acute occlusion of the intracranial arteries and occlusion at the origin of the vertebral artery confirmed by digital subtraction angiography were selected. The clinical data were summarized and analyzed. Results: Fifteen patients with VASS were enrolled in the study. The overall success rate of surgical recanalization was 80%. The successful proximal recanalization rate was 70.6%, and the recanalization rates for P1, P2, P3, and P4 were 100%, 71.4%, 50%, and 66.67%, respectively. The mean operation times for the A1 and A2 types were 124 and 120 â€‹min, respectively. The successful distal recanalization rate was 91.7%, and the recanalization rates for types D1, D2, D3, and D4 were 100%, 83.3%, 100%, and 100%, respectively. Five patients experienced perioperative complications (incidence rate: 33.3%). Distal embolism occurred in three patients (incidence rate: 20%). No dissection or subarachnoid hemorrhage occurred in any patient. Conclusion: EVT is a technically feasible treatment for VASS, and comprehensive PAD classification can, to a certain extent, help initially estimate the difficulty of surgery and provide guidance for interventional procedures.

Associations between NIHSS sub-item scores and prognosis and intracranial hemorrhage after endovascular therapy for acute anterior circulation ischemic stroke.

Purpose: The relationship between sub-item scores on the National Institutes of Health Stroke Scale (NIHSS) scores and prognosis and intracranial hemorrhage in patients with acute ischemic stroke undergoing endovascular treatment (EVT) has been insufficiently studied. The aim of this study was to investigate the correlation between NIHSS sub-item scores, prognosis, and intracranial hemorrhage. Methods: This study included patients with acute anterior circulation ischemic stroke undergoing EVT between February 2019 and April 2022. The outcomes included functional independence, defined as a modified Rankin Scale (mRS) score ≤ 2 at 3 months after EVT, intracranial hemorrhage within 24 h after EVT, and mortality within 3 months. A multivariate regression analysis was performed, including NIHSS sub-item scores and other adjusted variables. Results: A total of 568 patients were enrolled. Of the 568 patients, 239 (45%) achieved functional independence at 3 months after EVT. The median age in this group was 63 years (IQR 52-69) and 176 (73.6%) were male patients. Intracranial hemorrhage within 24 h after EVT occurred in 170 (30%) patients. The median age in this group was 65 years (IQR 56-71) and 105 (61.8%) were male patients. In a multivariate analysis adjusted for age, gender, and factors with a value of p of <0.05, the NIHSS limb movement sub-item score was strongly associated with prognosis at 3 months (OR 0.833, 95% CI 0.758-0.915) and intracranial hemorrhage within 24 h after EVT (OR 1.161, 95% CI 1.037-1.300). Conclusion: Higher limb movement sub-item scores on the NIHSS were independently associated with a poorer prognosis at 3 months and a higher rate of intracranial hemorrhage within 24 h after EVT among patients with acute anterior circulation ischemic stroke.

Improving neurological outcome for acute basilar artery occlusion with sufficient recanalization after thrombectomy by intraarterial tenecteplase (INSIST-IT): Rationale and design.

BACKGROUND: The potential benefit of intraarterial tenecteplase in acute basilar artery occlusion (BAO) patients with successful reperfusion following endovascular treatment (EVT) has not been studied. AIMS: To explore the efficacy and safety of intraarterial tenecteplase in acute BAO patients with successful reperfusion after EVT. SAMPLE SIZE ESTIMATES: A maximum of 228 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by center. DESIGN: We will conduct a prospective, randomized, adaptive-enrichment, open-label, blinded-end point, multicenter trial. Eligible BAO patients with successful recanalization after EVT [modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3] will be randomly assigned into the experimental and control group with a 1:1 ratio. Patients in the experimental group will receive intraarterial tenecteplase (0.2-0.3 mg/min for 20-30 min), while patients in the control group will receive routine treatment according to the usual practice of each center. Patients in both groups will receive standard guideline-based medical treatment. OUTCOME: The primary efficacy endpoint is a favorable functional outcome, defined as the modified Rankin Scale 0-3 at 90 days after randomization. The primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 48 h after randomization. Subgroup analysis of the primary outcome will be performed by age, gender, baseline NIHSS score, baseline pc-ASPECTS, intravenous thrombolysis, time from estimated symptom onset to treatment, mTICI, blood glucose, and stroke etiology. CONCLUSIONS: The results of this study will provide evidence of whether adjunct use of intraarterial tenecteplase after successful reperfusion with EVT is associated with better outcomes for acute BAO patients.

Intracranial hemorrhage in large vessel occlusion patients receiving endovascular thrombectomy with or without intravenous alteplase: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: Alteplase before thrombectomy for patients with large vessel occlusion stroke raises concerns regarding an increased risk of intracranial hemorrhage (ICH), but the details of this relationship are not well understood. METHODS: This was a secondary analysis of the DIRECT-MT trial. ICH and its subtypes were independently reviewed and classified according to the Heidelberg Bleeding Classification. The effects of alteplase before thrombectomy on ICH and ICH subtypes occurrence were evaluated using logistic regression. Clinical and imaging characteristics that may modify these effects were exploratorily tested. RESULTS: Among 591 patients, any ICH occurred in 254 (43.0%), including hemorrhagic infarction type 1 in 12 (2.1%), hemorrhagic infarction type 2 in 127 (21.7%), parenchymal hematoma type 1 in 34 (5.8%), parenchymal hematoma type 2 in 50 (8.6%), and other hemorrhage types (3a-3c) in 24 (4.1%). Similar ICH frequencies were observed with combined alteplase and thrombectomy versus thrombectomy only (134/292 (45.9%) vs 120/299 (40.1%); OR 1.27, 95% CI 0.91 to 1.75, P=0.16), but patients treated with alteplase had a higher parenchymal hematoma rate (51/287 (17.8%) vs 33/297 (11.1%); OR 1.75, 95% CI 1.08 to 2.85, P=0.024). In the adjusted model, difference in parenchymal hematoma occurrence between groups remained significant (adjusted OR 1.71, 95% CI 1.00 to 2.92, P=0.049). Patients with history of diabetes (Pinteraction=0.048), hypertension (Pinteraction=0.02), antiplatelet therapy (Pinteraction=0.02), anticoagulation therapy (Pinteraction=0.04), and statin administration (Pinteraction=0.02) harbored a higher ICH rate when they received combination therapy. CONCLUSIONS: Our data showed that in the DIRECT-MT trial, alteplase did not increase overall ICH for large vessel occlusion patients treated with thrombectomy, but it increased the parenchymal hematoma rate.

Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Rescue thrombolysis for medium vessel occlusion (RESCUE-TNK): Rationale and design of a phase 2 randomized trial.

Background: The best reperfusion strategy for medium-sized vessel occlusion (MeVO) is not well established. Given the proven treatment effect of intra-arterial thrombolysis in patients with large vessel occlusion (LVO), we hypothesized that intra-arterial tenecteplase (TNK) could increase the recanalization rate of MeVO and thus improve clinical outcome. Aims: To explore the safety and efficacy of intra-arterial TNK in patients with MeVO. Sample size estimates: A maximum of 80 patients are required to test the superiority hypothesis, using power = 80% and α = 0.025 to conduct the one-sided test. Design: Rescue treatment for mEdium veSsel oCclUsion by intra-artErial TNK (RESCUE-TNK) is a pilot, randomized, open-label, blinded end point, and multicenter trial. Eligible patients including primary MeVO as detected by the first DSA examination or secondary MeVO after endovascular treatment (EVT) for LVO will be assigned into the experimental group and control group as a ratio of 1:1. The experimental group will be treated with intra-arterial TNK (0.2-0.3 mg/min, for 20-30 min) via a microcatheter placed proximal to the site of occlusion, and the control group will be treated with routine therapy. Both groups of patients will be given standard stroke care based on the guidelines. Outcome: The primary efficacy end point is successful recanalization of MeVO, defined as the expanded treatment in cerebral ischemia (eTICI) score 2b67-3 after the procedure, while the primary safety end point is symptomatic intracranial hemorrhage (sICH), defined as National Institutes of Health Stroke Scale score increase ≥4 caused by intracranial hemorrhage within 24 (-6/+24) hours after randomization. Conclusion: The results of RESCUE-TNK will provide evidence for the efficacy and safety of intra-arterial TNK in the recanalization of patients with MeVO.

Neck-brain integrated ultrasound as a noninvasive screening tool to identify morphological features of middle cerebral artery disease.

BACKGROUND AND AIMS: Endovascular treatment is suitable for middle cerebral artery (MCA) with focal lesion. Therefore, accurate evaluation of the morphological features of MCA disease is critical. Ultrasonography is commonly used to screen for MCA lesions. However, there are few studies on lesion length. Using ultrasonography, we aimed to prospectively evaluate MCA disease with focal stenosis, long stenosis, focal occlusion, and long occlusion. METHODS: Patients with symptomatic MCA disease scheduled for digital subtraction angiography were enrolled. The ultrasonic parameters recorded included mean flow velocity at MCA (VMCA) and extracranial internal carotid artery (VICA), bilateral VMCA ratio, bilateral VICA ratio, and MCA flow continuity. RESULTS: A total of 278 MCAs were included. Compared to normal vessels, the bilateral VMCA ratio increased in the focal stenosis group and decreased in the long lesion and focal occlusion groups (all p < 0.05); the VICA and bilateral VICA ratio decreased in the long lesion group (all p < 0.01), and there was no significant difference in the focal lesion group (all p > 0.05). The optimal cut-offs were bilateral VMCA ratio <0.80 to predict long lesions and focal occlusions (sensitivity: 0.898, specificity: 0.975), and bilateral VICA ratio <0.84 to predict long lesions (sensitivity: 0.704, specificity: 0.879). The sensitivity and specificity to predict long occlusions were 96.7% and 94.8%, respectively, in the absence of MCA flow continuity. CONCLUSIONS: Neck-brain integrated ultrasound is an appropriate screening method for identifying MCA lesions with different morphologies. Endovascular treatment might not be recommended when bilateral VICA ratio <0.84 in patients with MCA lesions.

A sensitive triple nanoparticle-assisted PCR assay for detection of fowl adenovirus, infectious bursal disease virus and chicken anemia virus.

Fowl adenovirus (FAdV) infections in chickens have resulted in global economic losses in the poultry industry. Infectious bursal disease virus (IBDV) and chicken anemia virus (CAV) infections lead to immunosuppression in chickens, and concomitant co- infection with FAdV usually produces severe and lethal infections. These co-infections are common occurrences on chicken farms and affect large number of chickens. Thus, a rapid, sensitive and specific diagnostic test for these viruses becomes a prerequisite to effective control and isolation measures. We developed a triplex nanoparticle-assisted PCR (nano-PCR) assay that can simultaneously detect these 3 viruses in a single assay tube using PCR primers directed at respective specific genes of each virus. The assay was specific for FAdVs, CAV and IBDV, and it did not amplify Newcastle disease virus, infectious bronchitis virus, egg drop syndrome virus or Marek's disease virus. The minimum detection limit was 27.2 femtogram (fg) for all three viruses and was 1000-fold more sensitive than multiplex PCR using identical primers. Screening of 69 clinical samples from 40 to 50 days old chickens with obvious lesions in liver using the nano-PCR compared with a multiplex PCR yielded identical results. Of the 69 samples, 13 were detected positive including 4 for FAdV, 4 for IBDV and 6 for CAV single virus infections, respectively, as well as 5 for FAdV/CAV, 2 for FAdV/IBDV and 3 for IBDV/CAV co-infections. The triple nano-PCR assay developed in our laboratory is a sensitive, specific and simple method that can be used for detection of FAdV, CAV and IBDV as single or mixed infections.