Explore the vast range of titles available.

Background The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. Methods We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. Results Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p  < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection ( p  < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) ( p  < 0.0001). Conclusion Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.

Abstract Large vessel occlusions (LVOs), variably defined as blockages of the proximal intracranial anterior and posterior circulation, account for approximately 24% to 46% of acute ischemic strokes. Commonly refractory to intravenous tissue plasminogen activator (tPA), LVOs place large cerebral territories at ischemic risk and cause high rates of morbidity and mortality without further treatment. Over the past few years, an abundance of high-quality data has demonstrated the efficacy of endovascular thrombectomy for improving clinical outcomes in patients with LVOs, transforming the treatment algorithm for affected patients. In this review, we discuss the epidemiology, pathophysiology, natural history, and clinical presentation of LVOs as a framework for understanding the recent clinical strides of the endovascular era. Video Abstract 10.1093/neuros/nyz042 Video Abstract 10.1093.neuros.nyz042 6045763607001

Background Cerebral ischemia–reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated. Methods We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen–glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization. Results The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2–3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood–brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5’ adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments. Conclusions Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.

Endovascular Thrombectomy (EVT) as first-line treatment of patients with large core ischemic infarct is a subject of debate. A systematic literature search was conducted in four electronic databases for randomized control trials (RCTs) comparing EVT to best medical treatment (BMT) for large core infarcts (ASPECTS ≤ 5). Relevant studies were added after screening for titles, abstracts, and complete text. Meta-analysis was performed. The continuous outcomes were analyzed using the standardized mean difference (SMD) and 95% CI, while the binary outcomes were analyzed using the risk ratio (RR) and 95% confidence interval (CI). A funnel plot was used to visually evaluate publication bias, and if feasible, Egger's test was used to validate. We included 1918 patients from six RCTs that compared EVT plus BMT and BMT alone in patients with large core infarct due to large vessel occlusion in the anterior circulation. There were 946 patients in the EVT group and 972 patients in the BMT group. The one-year outcomes are available for 314 patients in the EVT group and 292 patents in the BMT group from two RCTs. EVT group had statistically significant higher rate of 90-day mRS 0–1 (RR = 3.1, P-value < 0.0001), mRS 0–2 (RR = 2.64, P-value < 0.0001), mRS 0–3 (RR = 1.80, P-value < 0.0001), lower 90-day mean mRS score (SMD = -0.29, P-value < 0.0001), lower 90-day mortality rate (RR = 0.85, P-value = 0.015), and greater early neurological improvement (RR = 2.16, P-value < 0.00001) compared to the BMT group. However, the rates of symptomatic intracerebral hemorrhage (sICH) (RR = 1.76, P-value = 0.01) and any ICH (RR = 2.18, P-value < 0.00001) were higher in EVT group. Our finding showed that EVT plus BMT led to in an absolute improvement of 5%, 12%, and 16% in 90-day mRS 0–1, 0–2, and 0–3, respectively. In addition, patients in EVT plus BMT group had a 3% increased probability of experiencing sICH and were 32% more susceptible to any ICH. Moreover, the one-year mRS 0–2 (RR = 2.16, P-value < 0.00001) and mRS 0–3 (RR = 1.80, P-value < 0.0001) was significantly favor the EVT plus BMT over BMT alone. Although, the one-year mortality rate was not significantly differed between two groups (RR = 0.91, P-value = 0.31). There was no statistically significant difference observed between the EVT plus BMT group and the BMT group concerning new stroke, decompressive craniectomy, and serious adverse events. Combined data from six RCTs shows that EVT plus BMT provides significantly better short- and long-term functional outcomes with minimal increase in symptomatic hemorrhage over BMT in patient with large core infarcts.

This study seeks to propose a novel framework for the ethical justification of randomized controlled trials (RCTs). This paper develops a novel framework for the ethical evaluation of RCTs, explored through the example of trials on endovascular thrombectomy for acute ischemic stroke. We propose that RCTs can be categorized into four quadrants, where justification in each quadrant relates to different thresholds for permissibility (the ethical defensibility of the trial) and necessity (the social and scientific importance of conducting the trial). Trials can be situated within four quadrants based on the interventions being compared: standard vs standard treatment in the alpha quadrant, standard vs novel treatment in the beta quadrant, standard vs no treatment in the gamma quadrant, and no treatment vs novel treatment in the delta quadrant. In each quadrant, the thresholds to establish permissibility and necessity will differ. The controversies that surrounded trials of thrombectomy for acute stroke can be understood as representing differing points of view about whether those trials should have been situated in the beta or delta quadrant. These differing conclusions highlight the importance of using a quadrant-based analysis in assessing the ethical permissibility and necessity of RCTs. The proposed four quadrants framework provides a comprehensive and precise approach to assessing the ethical justification of RCTs. Implementing this framework could improve regulatory evaluations of RCTs and reduce unnecessary harm to trial participants, while balancing the objectives of scientific advancement. In medical research, randomized controlled trials (RCTs) are used to test how well treatments work. However, RCTs can place patients at risk, so they should be ethically justified. This paper introduces a “four quadrants” framework to help determine when trials are ethically justified. The method proposed in this paper divides RCTs into four categories, or quadrants, based on their epistemic circumstances, or what is known about the treatments being compared. First is the alpha quadrant, in which trials compare two standard treatments. Second is the beta quadrant, in which trials compare a standard treatment with a standard plus a new treatment. Third, the gamma quadrant includes trials that compare a standard treatment with no treatment. Fourth, the delta quadrant includes trials that compare a new treatment with no treatment. The trials matter because the strength of the case to conduct a trial in any one of these quadrants will be different based on the strength of the argument necessary to prove that it is both permissible (one could do it) and necessary (one should do it). Using this methodology, we analyzed the case of endovascular thrombectomy trials for acute ischemic stroke conducted in the 2010s. We show that analysis using the four quadrants approach helps to understand the ethical controversy that beset these trials and offers a way forward in terms of resolving future potential conflicts. [Display omitted] •A novel framework for assessing the ethical justification of RCTs.•This paper provides a more comprehensive approach to the ethical justification of RCTs.•This framework could be used by researchers, regulators, and funders to analyze the ethics of RCTs.

Hemorrhagic transformation (HT) is one of the most serious complications after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) patients. The purpose of this study is to develop and validate deep‐learning (DL) models based on multiparametric magnetic resonance imaging (MRI) to automatically predict HT in AIS patients. Multiparametric MRI and clinical data of AIS patients with EVT from two centers (data set 1 for training and testing: n = 338; data set 2 for validating: n = 54) were used in the DL models. The acute infarction area of diffusion‐weighted imaging (DWI) and hypoperfusion of perfusion‐weighted imaging (PWI) was labeled manually. Two forms of data sets (volume of interest [VOI] data sets and slice data sets) were analyzed, respectively. The models based on single parameter and multiparameter models were developed and validated to predict HT in AIS patients after EVT. Performance was evaluated by area under the receiver‐operating characteristic curve (AUC), accuracy (ACC), sensitivity, specificity, negative predictive value, and positive predictive value. The results showed that the performance of single parameter model based on MTT (VOI data set: AUC = 0.933, ACC = 0.843; slice data set: AUC = 0.945, ACC = 0.833) and TTP (VOI data set: AUC = 0.916, ACC = 0.873; slice data set: AUC = 0.889, ACC = 0.818) were better than the other single parameter model. The multiparameter model based on DWI & MTT & TTP & Clinical (DMTC) had the best performance for predicting HT (VOI data set: AUC = 0.948, ACC = 0.892; slice data set: AUC = 0.932, ACC = 0.873). The DMTC model in the external validation set achieved similar performance with the testing set (VOI data set: AUC = 0.939, ACC = 0.884; slice data set: AUC = 0.927, ACC = 0.871) (p > 0.05). The proposed clinical, DWI, and PWI multiparameter DL model has great potential for assisting the periprocedural management in the early prediction HT of the AIS patients with EVT. The proposed DWI, PWI, and clinical multiparameter DL model may provide a potential tool for predicting information before therapy to assist the periprocedural management in AIS patients with EVT.

PurposeTo provide an update about the rapidly developing changes in the critical care management of acute ischaemic stroke patients.MethodsA narrative review was conducted in five general areas of acute ischaemic stroke management: reperfusion strategies, anesthesia for endovascular thrombectomy, intensive care unit management, intracranial complications, and ethical considerations.ResultsThe introduction of effective reperfusion strategies, including IV thrombolysis and endovascular thrombectomy, has revolutionized the management of acute ischaemic stroke and transformed outcomes for patients. Acute therapeutic efforts are targeted to restoring blood flow to the ischaemic penumbra before irreversible tissue injury has occurred. To optimize patient outcomes, secondary insults, such as hypotension, hyperthermia, or hyperglycaemia, that can extend the penumbral area must also be prevented or corrected. The ICU management of acute ischaemic stroke patients, therefore, focuses on the optimization of systemic physiological homeostasis, management of intracranial complications, and neurological and haemodynamic monitoring after reperfusion therapies. Meticulous blood pressure management is of central importance in improving outcomes, particularly in patients that have undergone reperfusion therapies.ConclusionsWhile consensus guidelines are available to guide clinical decision making after acute ischaemic stroke, there is limited high-quality evidence for many of the recommended interventions. However, a bundle of medical, endovascular, and surgical strategies, when applied in a timely and consistent manner, can improve long-term stroke outcomes.

Background and purpose The benefit and safety of intravenous thrombolysis before endovascular thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion (BAO) remains unclear. This article aims to investigate the clinical outcomes and safety of endovascular thrombectomy with versus without intravenous thrombolysis in acute BAO stroke patients. Methods We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases to identify relevant literature pertaining to patients with acute BAO who underwent endovascular thrombectomy alone or intravenous thrombolysis bridging with endovascular thrombectomy (bridging therapy), until January 10, 2024. The primary outcome was functional independence, defined as a score of 0–2 on the modified Rankin Scale at 90 days. The safety outcome was mortality at 90 days and symptomatic intracranial hemorrhage within 48 h. Effect sizes were computed as risk ratio (RR) with random-effect models. This study was registered in PROSPERO (CRD42023462293). Results A total of 528 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded. Finally, 2 RCTs and 10 cohort studies met the inclusion criteria. The findings revealed that the endovascular thrombectomy alone group had a lower rate of functional independence compared to the bridging therapy group (29% vs 38%; RR 0.78, 95% CI 0.68–0.88, p  < 0.001), lower independent ambulation (39% vs 45%; RR 0.89, 95% CI 0.82–0.98, p  = 0.01), and higher mortality (36% vs 28%, RR 1.22, 95% CI 1.08–1.37, p  = 0.001). However, no differences were detected in symptomatic intracranial hemorrhage between the two groups (6% vs 4%; RR 1.12, 95% CI 0.74–1.71, p  = 0.58). Conclusion Intravenous thrombolysis plus endovascular thrombectomy seemed to led to better functional independence, independent ambulation, and lower risk of mortality without increasing the incidence of intracranial hemorrhage compared to endovascular thrombectomy alone. However, given the non-randomized nature of this study, further studies are needed to confirm these findings.

The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840–0.942), the Hosmer–Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.