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High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100–129 mm Hg) or a standard care systolic blood pressure target group (130–185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24–36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites. Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24–36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60–1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. An intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24–36 h as compared with a standard care systolic blood pressure target of 130–185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. French Health Ministry.

Positive susceptibility vessel sign (SVS) in patients with acute ischaemic stroke has been associated with friable red blood cell-rich clots and more effective recanalisation using stent retrievers versus contact aspiration. We compared the safety and efficacy of stent retrievers plus contact aspiration (combined technique) versus contact aspiration alone as the first-line thrombectomy technique in patients with acute ischaemic anterior circulation stroke and SVS-positive occlusions. Adaptive Endovascular Strategy to the Clot MRI in Large Intracranial Vessel Occlusion (VECTOR) was a prospective, randomised, open-label study with blinded evaluation. Patients with SVS-positive anterior circulation occlusions on pretreatment MRI and arterial puncture within 24 h of symptom onset were enrolled from 22 centres in France. A centralised web-based method was used by interventional neuroradiologists for dynamic randomisation by minimisation. Patients were randomly assigned 1:1 to the combined technique or contact aspiration alone. The primary outcome was expanded Thrombolysis in Cerebral Infarction (eTICI) grade 2c or 3 reperfusion after three or fewer passes on post-treatment angiogram, adjudicated by a blinded independent central imaging core laboratory. The intention-to-treat population was used to assess the primary and secondary outcomes. This trial is registered with ClinicalTrials.gov (NCT04139486) and is complete. Between Nov 26, 2019, and Feb 14, 2022, 526 patients were enrolled, of whom 521 constituted the intention-to-treat population (combined technique, n=263; contact aspiration alone, n=258). The median age of participants was 74·9 years (IQR 64·4–83·3); 284 (55%) were female and 237 (45%) male. The primary outcome did not differ significantly between groups (152 [58%] of 263 patients for the combined technique vs 135 [52%] of 258 for contact aspiration; odds ratio [OR] 1·27; 95% CI 0·88–1·83; p=0·19). Procedure-related adverse events occurred in 32 (12%) of 263 patients in the combined technique group and 27 (11%) of 257 in the contact aspiration group (OR 1·14; 0·65–2·00; p=0·65). The most common adverse event was intracerebral haemorrhage (146 [56%] of 259 patients for the combined technique vs 123 [49%] of 251 for contact aspiration; OR 1·32; 0·91–1·90; p=0·13). All-cause mortality at 3 months occurred in 57 (23%) of 251 patients in the combined technique group and 48 (19%) of 247 in the contact aspiration group (OR 1·19; 0·76–1·86; p=0·45), none of which was treatment-related. The results of the VECTOR trial do not show superiority of the combined stent retriever plus contact aspiration technique over contact aspiration alone in patients with SVS-positive occlusion with respect to achieving eTICI 2c–3 within three passes. These findings support the use of either the combined technique or contact aspiration alone as the initial thrombectomy strategy in patients with acute anterior circulation stroke with SVS on pretreatment MRI. Cerenovus.

Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection is associated with high mortality rates and respiratory compromise in which excessive neutrophil extracellular trap (NET) production may amplify alveolar inflammation and injury. Dornase alfa, a recombinant DNAse 1, has been proposed to attenuate these effects by degrading extracellular DNA and enhancing alveolar clearance of NETs. In this multicenter, open-label, randomized in two parallel arms (1:1) controlled trial, intubated COVID-19 ARDS patients received either standard-of-care (SOC) alone or SOC plus aerosolized dornase alfa (2500 IU twice daily for 7 days). The primary endpoint was the proportion of patients with ARDS severity improvement at Day 7, defined by at least one-grade improvement on the Berlin criteria scale. Secondary outcomes included 28-day mortality, ventilator-free days, ICU-free days, and changes in key ventilatory parameters. Biological samples were analyzed to assess NET related markers, DNAse drug activity and indicate possible bioavailability issues associated with aerosolization of dornase alfa. Seventy-seven patients were enrolled (dornase alfa group, n  = 39; SOC group, n  = 38). At Day 7, ARDS severity improved in 18% of patients receiving dornase alfa compared with 29% in the SOC group (adjusted OR: 0.33; 95% CI 0.09–1.14; p  = 0.11). Secondary endpoints, including 28-day mortality, ventilator-free days, and ICU-free days, showed no significant differences between groups. Adverse events occurred in 38.5% of patients in the dornase alfa arm versus 31.6% in the SOC arm, indicating comparable safety profiles. Despite early increases in NET plasmatic levels observed in both groups and successful ex vivo NET degradation, aerosolized dornase alfa failed to significantly enhance DNAse activity or reduce NET-related markers in patients’ plasma and mucus, suggesting potential bioavailability limitations with this delivery method. In patients with COVID-19-related ARDS, dornase alfa did neither significantly reduce ARDS severity nor improve clinical outcomes over SOC. Although well tolerated, analysis of biological samples suggests that aerosol administration may have compromised drug bioavailability. Further trials are needed to determine whether specific patient subgroups could benefit more from dornase alfa or if alternative drug delivery methods might enhance treatment efficacy. ClinicalTrials.gov, NCT04355364. Registered on 21/04/2020.

BackgroundEndovascular treatment (EVT) failures and early reocclusions in stroke often result from arterial wall disease, incomplete thrombus withdrawal, or acute endothelial injury. Intracranial and extracranial atherosclerosis, in particular, poses a risk of reocclusion, sometimes requiring tailored interventions (eg, angioplasty, stenting). While glycoprotein (GP) IIb/IIIa inhibitors have been widely studied in ischemic stroke, cangrelor remains less explored.ObjectiveTo evaluate the safety and efficacy of cangrelor compared with GPIIb/IIIa inhibitors in large vessel occlusion stroke (LVOS).MethodsThis retrospective analysis from the Endovascular Treatment in Ischemic Stroke Registry included patients from 34 French centers who received cangrelor or GPIIb/IIIa inhibitors during EVT between July 2018 and September 2023. Eligible cases had refractory occlusions or arterial disease at risk of reocclusion. The primary outcome was a 90-day favorable outcome. Secondary outcomes included excellent functional outcome, early neurological improvement, intracranial hemorrhage (ICH), procedural complications, and day 1 arterial patency. Propensity score overlap weighting was used for comparisons.ResultsOf 559 patients, 160 received GPIIb/IIIa inhibitors and 399 received cangrelor. Favorable outcomes were comparable (41.7% vs 43.7%; OR=1.1; 95% CI 0.61 to 1.93), as were rates of excellent functional outcome and early neurological improvement. Angiographic efficacy was similar, with modified Thrombolysis in Cerebral Infarction ≥2b rates of 89.5% for GPIIb/IIIa and 90.1% for cangrelor. No significant differences were observed in day 1 patency, 90-day mortality, or symptomatic ICH.ConclusionsCangrelor showed comparable safety and efficacy to GPIIb/IIIa inhibitors. These results, along with the specific pharmacodynamics, make this drug a promising agent in the acute management of complex intracranial and extracranial LVOS.Trial registration numberNCT03776877.

ObjectiveDuring thrombectomy, thromboembolic migration in previously unaffected territory may occur and is not systematically notified. We report our data on the incidence, predictors, and clinical outcome of anterior cerebral artery emboli (ACAE).MethodsFrom a prospectively collected thrombectomy database of consecutive patients with anterior circulation stroke between January 2012 and December 2016, 690 angiographic images were analyzed to assess ACAE. The primary outcome was a favorable outcome, defined as a 3 month modified Rankin Scale score of 0–2 or equal to the pre-stroke score.ResultsACAE occurred in 65 patients (9.4%; 95% CI 7.2% to 11.6%). Internal carotid artery occlusion (tandem or terminal), Alberta Stroke Program Early CT Score <7, increasing number of passes, and use of stent retriever alone (compared with distal aspiration alone or combined with stent retriever) were found to be independent predictors of ACAE. Compared with patients without ACAE, patients with ACAE had lower rates, with an adjusted OR (95% CI) of 0.48 (0.25 to 0.92; P=0.027) for favorable outcome and 0.49 (0.25 to 0.96; P=0.038) for early neurologic improvement. ACAE was significantly associated with a higher mortality (adjusted OR 1.93; 95% CI 1.03 to 3.61; P=0.039) and intracranial hemorrhagic complications (adjusted OR 2.45; 95% CI 1.33 to 4.47; P=0.004). Despite a successful reperfusion modified Thrombolysis in Cerebral Infarction score of 2b–3 at the end of the procedure, a favorable outcome was reached in 30% of patients with ACAE compared with 52.4% in the other patients (OR 0.39; 95% CI 0.19 to 0.78; P=0.008).ConclusionsProcedural ACAE was not an uncommon condition, and was associated with increased mortality and disability rates, regardless of the success of reperfusion.

BackgroundAccumulating evidence indicates that neutrophil activation (NA) contributes to microvascular thromboinflammation in acute ischemic stroke (AIS) due to a large vessel occlusion. Preclinical data have suggested that intravenous thrombolysis (IVT) before endovascular therapy (EVT) could dampen microvascular thromboinflammation. In this study we investigated the association between NA dynamics and stroke outcome, and the impact of IVT on NA in patients with AIS treated with EVT.MethodsA single-center prospective study was carried out, including patients treated with EVT for whom three blood samples (before, within 1 hour, 24 hours post-EVT) were drawn to measure plasma myeloperoxidase (MPO) concentration as a marker of NA. Unfavorable outcome was defined as a modified Rankin score of 3–6 at 3 months.ResultsBetween 2016 and 2020, 179 patients were included. The plasma MPO concentration peaked significantly 1 hour post-EVT (median increase 21.0 ng/mL (IQR −2.1–150)) and returned to pre-EVT baseline values 24 hours after EVT (median change from baseline −0.8 ng/mL (IQR −7.6–6.7)). This peak was strongly associated with unfavorable outcomes at 3 months (aOR 0.53 (95% CI 0.34 to 0.84), P=0.007). IVT before EVT abolished this 1 hour post-EVT MPO peak. Changes in plasma MPO concentration (baseline to 1 hour post-EVT) were associated with unfavorable outcomes only in patients not treated with IVT before EVT (aOR 0.54 (95% CI 0.33 to 0.88, P=0.013). However, we found no significant heterogeneity in the associations between changes in plasma MPO concentration and outcomes.ConclusionsA peak in plasma MPO concentration occurs early after EVT and is associated with unfavorable outcomes. IVT abolished the post-EVT MPO peak and may modulate the association between NA and outcomes.

Abstract BACKGROUND Occipital arteriovenous malformations (AVMs) carry a high risk of postoperative morbidity because of their anatomic relation to the visual cortex and optic radiations. Data regarding endovascular management of these lesions are scant. OBJECTIVE To report our single-center experience with occipital AVMs, most of which were treated endovascularly, with a special interest for postoperative visual impairment. METHODS From a prospective database, we assessed the clinical and radiological data of all patients with an occipital AVM managed between 1997 and 2018. The extension of the nidus to the primary visual cortex was assessed and correlated to the pre- and postintervention visual symptomatology. Modified Rankin Scale and visual fields (VFs) were assessed pre- and post-treatment and at the last follow-up. RESULTS A total of 83 patients (47 males [56.6%]) with an occipital AVM were included in the study. Mean age at presentation was 33.5 ± 15.0 yr (min-max = 7-76). A total of 34 patients (41%) presented with hemorrhage related to the AVM. A total of 57 patients (68.7%) underwent endovascular treatment (EVT) alone, 20 (24.1%) underwent embolization and surgery, 3 (3.6%) underwent embolization and radiosurgery, and 3 (3.6%) were conservatively managed. A complete obliteration of the AVM was achieved in 53 patients (66.3%). A post-treatment worsening of the VF was found in 24 of the treated patients (30%), 3 patients (9%) for ruptured AVMs, and in 21 patients (46%) for unruptured AVMs. Morbidity rate was 3.7% and mortality rate was 2.5%. CONCLUSION EVT of occipital AVM carries a non-negligible rate of complications, especially regarding visual functions. Graphical Abstract Graphical Abstract

An increasing number of centers not necessarily equipped with biplane (BP) angiosuites are performing mechanical thrombectomy (MT) in acute ischemic stroke patients. We assessed whether MT performed on single-plane (SP) is equivalent in terms of safety, effectiveness, radiation and contrast agent exposure. Consecutive patients treated by MT in four high volume centers between January 2014 and May 2017 were included. Demographic and MT characteristics were assessed and compared between SP and BP. Of 906 patients treated by MT, 576 (64%) were handled on a BP system. After multivariate analysis, contrast load and fluoroscopy duration were significantly lower in the BP group [100vs200mL, relative effect 0.85 (CI: 0.79–0.92), p = 0.0002; 22 vs 27 min, relative effect 0.84 (CI: 0.76–0.93), p = 0.0008, respectively]. There was no difference in recanalization (modified Thrombolysis-In-Cerebral-Infarction 2b-3), good clinical outcome (modified Rankin Scale 0–2), complications rates, procedure duration or radiation exposure. A three-vessel diagnostic angiogram performed prior to MT led to a significant increase in procedure duration (15% increase, p = 0.05), radiation exposure (33% increase, p < 0.0001) and contrast load (125% increase, p < 0.0001). Mechanical neuro-thrombectomy seems equally safe and effective on a single or biplane angiography system despite increased contrast load and fluoroscopy duration on the former.

BackgroundFew case reports have considered the chromatic aspect of retrieved clots and the possible association with their underlying etiology.ObjectiveThe aim of our study was to analyze the frequency of the TOAST ischemic stroke typical (atrial fibrillation, dissection, atheroma) and atypical (infective endocarditis, cancer-related, valve-related thrombi) etiologies depending on the chromatic aspect of retrieved clots.MethodsA total of 255 anonymized and standardized clot photos of consecutive patients treated by mechanical thrombectomy for acute ischemic stroke were included. A double-blind evaluation was performed by two senior interventional neuroradiologists, who classified the visual aspects of the clots into two main patterns: red/black or white. Main patient characteristics, distribution of underlying stroke etiologies, and outcomes were compared between the two study groups.ResultsThe inter-reader agreement for clot colors was excellent (k=0.78). Two hundred and thirty-three patients were classified as having red/black clots and 22 as having white clots. A statistically significant association (p=0.001) between atypical etiologies and white clots was observed.ConclusionsWhite clots were significantly associated with atypical etiologies in this cohort,in particular, with infectious endocarditis.