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Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76–3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83–3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0–2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12–24 h (common OR 5·86 [95% CI 3·14–10·94]) than those randomly assigned within 6–12 h (1·76 [1·18–2·62]; pinteraction=0·0087). These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window. Stryker Neurovascular.

Cerebral collateral status is considered an independent prognostic factor in stroke patients. We aimed to assess whether collateral extent also modifies first-pass recanalization (FPR) and distal emboli generation across different mechanical thrombectomy (MT) strategies. Two in-vitro neurovascular models were created: good (GCM) and poor collaterals model (PCM). Both were identical up to the M2 segment of the middle cerebral artery (MCA), but only the GCM included primary and secondary anastomoses. Soft (stiffness = 53.72 ± 5.32 kPa) and stiff (stiffness = 110.02 ± 10.59 kPa) clot analogs embolized the M1-MCA. The study was randomized for thrombectomy technique: direct aspiration thrombectomy, partial stent retriever retraction and complete stent retriever retraction. Outcome measures were: complete (TICI2c-3), substantial (TICI2b-3) recanalization, and distal emboli parameters. A total of 240 MTs were performed (20 experiments per technique/model/clot type). Overall rates of complete and substantial recanalization were 23.8% and 68.8% respectively. Complete recanalization was higher in GCM (33.3%) than in PCM (14.2%; p  < 0.01) regardless of clot type or technique. Across all clot types and collateral status, complete stent-retriever technique achieved highest rate of TICI 2b-3 and direct aspiration the highest rates of TICI 2c-3, particularly in PCM. Partial stent-retriever retraction technique was the least effective. In our experimental setup, there were no significant differences in distal embolization according to collaterals or clot types, however partial stent-retriever retraction technique generated the highest embolic load and direct aspiration the lowest. The degree of collateral circulation may modify MT angiographic outcomes with different impacts according to techniques or clot composition and could be used to guide therapeutic decisions.

BackgroundA repeated number of passes during mechanical thrombectomy leads to worse clinical outcomes in acute ischemic stroke. Initial experiences with the simultaneous double stent-retriever (double-SR) technique as the first-line treatment showed promising safety and efficacy results.ObjectiveTo characterize the potential benefits of using the double-SR as first-line technique as compared with the traditional single-SR approach.MethodsThree types of clot analogs (soft, moderately stiff, and stiff) were used to create terminal internal carotid artery (T-ICA=44) and middle cerebral artery (MCA=88) occlusions in an in vitro neurovascular model. Sixty-six cases were randomized into each treatment arm: single-SR or double-SR, in combination with a 0.071\" distal aspiration catheter. A total of 132 in vitro thrombectomies were performed. Primary endpoints were the rate of first-pass recanalization (%FPR) and procedural-related distal emboli.ResultsFPR was achieved in 42% of the cases. Overall, double-SR achieved a significantly higher %FPR than single-SR (52% vs 33%, P=0.035). Both techniques showed similar %FPR in T-ICA occlusions (single vs double: 23% vs 27%, P=0.728). Double-SR significantly outperformed single-SR in MCA occlusions (63% vs 38%, P=0.019), most notably in saddle occlusions (64% vs 14%, P=0.011), although no significant differences were found in single-branch occlusions (64% vs 50%, P=0.275). Double-SR reduced the maximal size of the clot fragments migrating distally (Feret diameter=1.08±0.65 mm vs 2.05±1.14 mm, P=0.038).ConclusionsThis randomized in vitro evaluation demonstrates that the front-line double-SR technique is more effective than single-SR in achieving FPR when treating MCA bifurcation occlusions that present saddle thrombus.

In this randomized trial involving patients with acute ischemic stroke with proximal anterior circulation occlusion, endovascular treatment with a Solitaire stent retriever was more effective than medical therapy alone in improving functional outcomes at 90 days. Recently completed prospective, randomized trials involving patients with acute stroke have consistently shown a clinical benefit for mechanical thrombectomy. 1 – 4 Our study, called the Randomized Trial of Revascularization with Solitaire FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset (REVASCAT), shares the following four features with the previously cited trials: enrollment limited to patients with imaging-based evidence of proximal occlusion of the M1 segment (main trunk) of the middle cerebral artery with or without concomitant occlusion of the internal carotid artery, imaging-based exclusion . . .

Background: Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches. Methods: We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. Results: Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3–43.6; p < 0.001] and 32.1 min (95% CI: 15.1–49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer (n = 1753) and mothership patients (n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97–1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups. Conclusion: DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients. Registration: This study was registered in PROSPERO (CRD42020213621).

The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11–78.42; p  = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50–0.95; p  = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64–26.42, p  = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23–13.03; p  = 0.021), and smoking (OR 2.91, 95% CI 1.08–7.90; p  = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83–0.94; p  < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.

ObjectiveTo evaluate direct transfer to the angiosuite protocol of patients with acute stroke, candidates for endovascular treatment (EVT).MethodsWe studied workflow metrics of all patients with stroke who had undergone EVT in the past 12 months. Patients followed three protocols: direct transfer to emergency room (DTER), CT room (DTCT) or angiosuite (DTAS, only last 6 months if admission National Institute of Health Stroke Scale (NIHSS) score >9 and time from onset <4.5 hours) according to staff/suite availability. DTAS patients underwent cone-beam CT before femoral puncture. Dramatic clinical improvement was defined as 10 NIHSS points drop at 24 hours.Results201 patients were included: 87 DTER (43.3%), 74 DTCT (36.8%), 40 DTAS (19.9%).Ten DTAS patients (25%) did not receive EVT: 3 (7.5%) showed intracranial hemorrhage on cone-beam CT and 7 (17.5%) did not show an occlusion on angiography. Mean door-to-puncture (D2P) time was shorter in DTAS (17±8 min) than DTCT (60±29 min; p<0.01). D2P was longer in DTER (90±53 min) than in the other protocols (p<0.01). For outcome analyses only patients who received EVT were compared; no significant differences in baseline characteristics, including time from symptom-onset to admission, puncture-to-recanalization, or recanalization rate, were seen. However, time from symptom-to-puncture (DTAS: 197±72 min, DTER: 279±156, DTCT: 224±142 min; p=0.01) and symptom-to-recanalization (DTAS: 257±74, DTER: 355±158, DTCT: 279±146 min; p<0.01) were longer in the DTER group. At 24 hours, there were no differences in NIHSS score (p=0.81); however, the rate of dramatic clinical improvement was significantly higher in DTAS: 48.6% (DTER 24.1%, DTCT 27.4%); p=0.01). An adjusted model pointed to shorter onset-to-puncture time as an independent predictor of dramatic improvement (OR=1.23, 95% CI 1.13 to 133; p<0.01)ConclusionIn a subgroup of patients direct transfer and triage in the angiosuite seems feasible, safe, and achieves significant reduction in hospital workflow times.

BackgroundEndovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke (AIS) due to large vessel occlusion. However, many patients fail to achieve good outcomes, especially without first pass reperfusion. Intra-arterial thrombolytics such as recombinant tissue plasminogen activator (rtPA) and tirofiban have shown potential as adjunctive therapies. The aim of this study was to compare the in vitro effects of rtPA, tirofiban, and their sequential combination on EVT retrieved clots.MethodsHuman clot obtained during EVT was tested in an in vitro model of cerebral circulation. A three-dimensional printed arterial flow loop was used to replicate middle cerebral artery circulation. Clots were exposed to four treatment arms: plasma (control), rtPA, tirofiban, or both rtPA and tirofiban sequentially. Thrombolytic efficacy was quantified by clot weight reduction with multivariable statistical analyses adjusted by clinical variables.Results70 clots were collected and used to perform 172 thrombolytic experiments. Both rtPA and tirofiban significantly reduced clot weight (tirofiban 20.6%, rtPA 20.7%, P<0.001), with a greater reduction when administered sequentially (37.9%, P<0.001). The treatment arm was the only significant predictor of thrombolytic effect. Clinical variables showed no statistically significant associations, although occlusion location and diabetes showed trends toward an association with clot weight reduction.ConclusionsThis study supports the use of clot based in vitro models with autologous plasma for standardized drug testing for patients with AIS. Sequential administration of rtPA and tirofiban resulted in greater clot degradation than either agent alone. Further studies are needed to confirm clinical applicability and optimize dual thrombolytic strategies.

BackgroundRapid identification of large vessel occlusion (LVO) in acute ischemic stroke (AIS) is essential for reperfusion therapy. Screening tools, including Artificial Intelligence (AI) based algorithms, have been developed to accelerate detection but rely heavily on pre-test LVO prevalence. This study aimed to review LVO prevalence across clinical contexts and analyze its impact on AI-algorithm performance.MethodsWe systematically reviewed studies reporting consecutive suspected AIS cohorts. Cohorts were grouped into four clinical scenarios based on patient selection criteria: (a) high suspicion of LVO by stroke specialists (direct-to-angiosuite candidates), (b) high suspicion of LVO according to pre-hospital scales, (c) and (d) any suspected AIS without considering severity cut-off in a hospital or pre-hospital setting, respectively. We analyzed LVO prevalence in each scenario and assessed the false discovery rate (FDR) - number of positive studies needed to encounter a false positive, if applying eight commercially available LVO-detecting algorithms.ResultsWe included 87 cohorts from 80 studies. Median LVO prevalence was: (a) 84% (77–87%), (b) 35% (26–42%), (c) 19% (14–25%), and (d) 14% (8–22%). At high prevalence levels: (a) FDR ranged between 0.007 (1 false positive in 142 positives) and 0.023 (1 in 43), whereas in low prevalence scenarios (Ccand d), FDR ranged between 0.168 (1 in 6) and 0.543 (over 1 in 2).ConclusionTo ensure meaningful clinical impact, AI algorithms must be evaluated within the specific populations and care pathways where they are applied.