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Background: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC., Methods: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system., Findings: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression., Interpretation: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC., Funding: The funding details can be found in the Acknowledgements section., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: In the treatment of intracranial arterial stenosis (ICAS), controversies remain regarding the optimal treatment strategy. Our study aims to conduct an individual patient-level data meta-analysis of existing RCTs comparing PTAS versus best medical therapy and to identify differences in outcomes such as incidence of ischemic stroke or death., Methods: Randomised controlled trials comparing the outcomes of stenting versus best medical therapy for patients who had symptomatic ICAS of >50%. Excluded studies included case reports, case series, reviews, observational studies,  letters or studies evaluating isolated angioplasty techniques without stenting. Data was extracted in accordance with PRISMA guidelines., Results: 7 studies involving 1425 participants were included. There was an increased risk in the incidence of stroke and death within the first 30 days post-procedure for patients treated with PTAS over best medical therapy (RR = 2.22 [1.28-3.86], I² = 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41-66.45], I² = 0%) and death (RR = 5.41 [1.20-24.28], I² = 0%).Under the shared frailty model, stenting when compared to medical therapy has a HR of 1.81 (95% CI:1.25-2.6) of stroke or death across 1 year. Under the parametric Royston-Parmar model, stenting has a significant decrease in the RMST(-0.83 months; 95% CI: -1.30-0.37). Stenting continued to show worse outcomes up to the 3 year mark with a HR of 1.60 (95% CI: 1.11-2.32)., Conclusions and Relevance: There is an increased risk of peri- and post-procedural stroke and death over best medical therapy in patients with symptomatic ICAS who undergo PTAS. Further work is required to refine patient selection and mitigate peri-procedural risks., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET., Methods: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months., Results: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders., Conclusion: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores., (© 2024. The Author(s).)

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic-RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic.

Background: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke (AIS) from basilar artery occlusion (BAO)., Objective: To compare the clinical outcomes of MT, with and without bridging intravenous thrombolysis (IVT), in acute BAO through a systematic review and meta-analysis of the current literature., Methods: Systematic searches of Medline, EMBASE, and Cochrane Central were undertaken on August 1, 2022. Good functional outcome defined as 90-day modified Rankin Scale score 0-2 was the primary outcome measure. Secondary outcome measures were 90-day mortality, successful post-thrombectomy recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and subarachnoid hemorrhage (SAH)., Results: Three studies reporting 1096 patients with BAO AIS were included in the meta-analysis. No significant differences in good functional outcome were detected between the two groups (RR=1.28 (95% CI 0.86 to 1.92); p=0.117). However, specifically patients with large artery atherosclerosis (LAA) benefited from bridging IVT (OR=2.52 (95% CI 1.51 to 4.22); p<0.001) with better functional outcomes. There was a significantly lower 90-day mortality rate for patients who underwent bridging IVT compared with MT alone (RR=0.70 (95% CI 0.62 to 0.80); p=0.008). No significant differences were detected in rates of post-treatment recanalization (RR=1.01 (95% CI 0.35 to 2.91); p=0.954), sICH (RR=0.96 (95% CI 0.66 to 1.42); p=0.724), and SAH (RR=0.93 (95% CI 0.31 to 2.83); p=0.563)., Conclusions: In patients with AIS due to BAO, bridging IVT was associated with lower mortality rates at 90 days, compared with direct MT. There were no improved functional outcomes or increased sICH or SAH between both arms, However, patients with LAA benefited from bridging IVT, with better functional outcomes., Competing Interests: Competing interests: GA: Stryker Neurovascular, Penumbra Inc, Medtronic: payments were received by the employer for consulting and proctoring assignments., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The role of mechanical thrombectomy (MT) in cerebral venous sinus thrombosis (CVT) is ambiguous. This study aims to share our experience with MT in CVT, supplemented by a meta-analysis on this treatment. All patients who had MT for CVT at our institution, between 2016 and 2021, were retrospectively reviewed for treatment indications, the technique used, success and complication rates, and clinical outcomes. A meta-analysis was performed for clinical and safety outcomes from published literature with > 10 patients. A total of 15 patients were included in this study. All had a venous hemorrhage or deteriorating despite anticoagulation. MT was performed using aspiration (with wide bore catheters) in 7 patients: aspiration with stent retriever in 5 and transjugular Fogarty-balloon thrombectomy in 3 patients. Adjunctive intra-sinus thrombolysis (IST) was used in 4 cases and venoplasty in 3. Technical success (restoring antegrade venous flow on arterial injection) was 100% with no procedure-related major complication. The direct transjugular approach was cheaper and faster. At 3-month follow-up, 86% of patients had good outcomes (MRS < 2). Meta-analysis of clinical and safety outcomes from 22 and 20 studies, respectively, demonstrated a positive association between MT and good outcomes as well as no significant association with hazardous periprocedural events. EVT via mechanical means for CVT is feasible in our series and meta-analysis. From our experience, trans-jugular Fogarty balloon embolectomy seems to be a potential cost-saving option, at least in a certain part of the world., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The use of a combination of balloon guide catheter (BGC), aspiration catheter, and stent retriever in acute ischemic stroke thrombectomy has not been shown to be better than a stent retriever and BGC alone, but this may be due to a lack of power in these studies. We therefore performed a meta-analysis on this subject., Methods: A systematic literature search was performed on PubMed, Scopus, Embase/Ovid, and the Cochrane Library from inception to October 20, 2021. Our primary outcomes were the rate of successful final reperfusion (Treatment in Cerebral Ischemia (TICI) 2c-3) and first pass effect (FPE, defined as TICI 2c-3 in a single pass). Secondary outcomes were 3 month functional independence (modified Rankin Scale score of 0-2), mortality, procedural complications, embolic complications, and symptomatic intracranial hemorrhage (SICH). A meta-analysis was performed using RevMan 5,4, and heterogeneity was assessed using the I 2 test., Results: Of 1629 studies identified, five articles with 2091 patients were included. For the primary outcomes, FPE (44.9% vs 45.4%, OR 1.04 (95% CI 0.90 to 1.22), I 2 =57%) or final successful reperfusion (64.5% vs 68.6%, OR 0.98 (95% CI 0.81% to 1.20%), I 2 =85%) was similar between the combination technique and stent retriever only groups. However, the combination technique had significantly less rescue treatment (18.8% vs 26.9%; OR 0.70 (95% CI 0.54 to 0.91), I 2 =0%). This did not translate into significant differences in secondary outcomes in functional outcomes, mortality, emboli, complications, or SICH., Conclusion: There was no significant difference in successful reperfusion and FPE between the combined techniques and the stent retriever and BGC alone groups. Neither was there any difference in functional outcomes, complications, or mortality., Competing Interests: Competing interests: LM received compensation as a speaker for Balt., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Pulmonary arteriovenous malformations (PAVMs) are uncommon, predominantly congenital direct fistulous connections between the pulmonary arteries and pulmonary veins, resulting in a right to left shunt. Patients with PAVMs are usually asymptomatic with lesions detected incidentally when radiological imaging is performed for other indications. In this review, we discuss the classification and radiological features of PAVMs as well as their treatment and follow-up options, with a particular focus on percutaneous endovascular techniques and the evolution of the available equipment for treatment.

Background: Endovascular thrombectomy (EVT) in large vessel occlusion (LVO) in anterior circulation acute ischaemic stroke (AIS) results in good functional outcomes in only approximately 60% of the patients. Internal cerebral veins (ICVs) are easily visible, with a consistent midline location, and are linked to stroke outcomes. We hypothesize that ICV asymmetry on multiphasic CT angiogram (mCTA) can be an adjunctive predictor for poor functional outcomes., Methods: We studied consecutive AIS patients from 2017 to 2019 with anterior circulation LVO treated with EVT regardless of intravenous thrombolysis. Asymmetrical ICV was defined as the presence of hypodensity (less opacification) on the ipsilateral occlusion side as compared with the contralateral side. The primary outcome was modified Rankin Score (mRS) score at 3 months. Secondary outcomes were good recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3), symptomatic hemorrhage, and mortality., Results: A total of 185 patients were included with a median age of 70 years (IQR 59-77); 87 patients (47%) were female. 82 patients (44.3%) achieved good functional outcomes (mRS 0-2) at 3 months. On multivariate analysis, National Institutes of Health Stroke Scale (NIHSS) (OR 1.076, 95% CI 1.015 to 1.140; p<0.013), poor collateral score (OR 0.285, 95% CI 0.162 to 0.501; p<0.001), asymmetrical ICV on the peak venous phase (OR 2.47, 95% CI 1.115 to 5.471; p<0.026), and late venous phase of the mCTA (OR 2.642, 95% CI 1.161 to 6.016; p<0.021) were independent risks factors of poor outcomes., Conclusion: ICV asymmetry is a novel radiological sign which is independently associated with poor functional outcomes in EVT, even after correction for collateral circulation. Further studies are needed to validate this finding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT)., Objective: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years., Methods: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation., Results: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002)., Conclusions: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO., Methods: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH)., Results: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups., Conclusion: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background and Purpose: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT., Methods: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH)., Results: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013)., Conclusions: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

Objective: To evaluate the efficacy of a barrier shield in reducing droplet transmission and its effect on image quality and radiation dose in an interventional suite., Methods: A human cough droplet visualisation model in a supine position was developed to assess efficacy of barrier shield in reducing environmental contamination. Its effect on image quality (resolution and contrast) was evaluated via image quality test phantom. Changes in the radiation dose to patient post-shield utilisation was measured., Results: Use of the shield prevented escape of visible fluorescent cough droplets from the containment area. No subjective change in line-pair resolution was observed. No significant difference in contrast-to-noise ratio was measured. Radiation dosage to patient was increased; this is predominantly attributed to the increased air gap and not the physical properties of the shield., Conclusion: Use of the barrier shield provided an effective added layer of personal protection in the interventional radiology theatre for aerosol generating procedures., Advances in Knowledge: This is the first time a human supine cough droplet visualisation has been developed. While multiple types of barrier shields have been described, this is the first systematic practical evaluation of a barrier shield designed for use in the interventional radiology theatre.

Endovascular thrombectomy (EVT) has been validated in several randomized controlled trials in recent years for its efficacy in the treatment of acute ischemic strokes (AIS) and is now the standard of care according to international guidelines. However, in about 20% of EVT procedures, recanalization is not achieved, and over 50% of patients who undergo EVT still do not have good functional outcome. In this article, we provide an extensive review of the latest evidence and developments in the field of EVT, with particular focus on the factors that improve patient outcomes. These factors include new and adjunctive techniques such as combination of direct aspiration and stent retriever, intra-arterial urokinase or 2b/3a inhibitors, rescue stenting, as well as novel devices including balloon guide catheters and the newer generations of aspiration catheters and stent retrievers. We also examined the latest notion of using first-pass effect (FPE) as the target to achieve during EVT, which has been associated with an improved functional outcome. While the field of EVT has been rapidly evolving, further research is required in specific AIS patient populations such as those with large ischemic core, late presentation beyond 24 h, posterior circulation strokes, and with distal medium vessel occlusion or tandem lesions to better assess its efficacy and safety., Competing Interests: TA is a consultant for Ablynx, Amnis Therapeutics, Medtronic, Cerenovus/J&J, Rapid Medical and Anaconda. AG is a consultant for Stryker, Medtronic, Penumbra and has received educational grants from Abbott. PB is consultant for Phenox. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yeo, Jing, Bhogal, Tu, Gopinathan, Yang, Tan, Arnberg, Sia, Holmin and Andersson.)

Objectives: The role of flow-diversion in acute sub-arachnoid haemorrhage (SAH) is controversial. Many of the published data warns of high rates of procedure-related complications and aneurysmal rebleed. This study evaluates the safety, efficacy, clinical and angiographic outcomes of acute flow-diversion at our institute., Methods: The institutional database from June 2015 to June 2020 was retrospectively reviewed for aneurysmal SAH (aSAH) treated with flow diversion. Clinical presentation, procedural details, complications, anti-platelet usage, rebleeding and aneurysm occlusion rates and outcomes were recorded., Results: 22 (59% females; median age 56 years) consecutive patients were identified. None of them were on regular antiplatelets/anticoagulation in the 15-days preceding the treatment. The mean aneurysm diameter was 5.4 mm and the median delay to flow-diversion was 2 days. Almost 73% (16/22) of patients had adjunctive coiling in the same session. There was no aneurysmal rebleed at a median follow up of 8.5 months and 86.3% (19/22 patients) had good clinical outcomes (3-month MRS 0-2). Adverse events related to the flow diversion procedure were seen in 3 patients; none of them had a medium to long-term clinical consequence. Three patients died from complications of SAH, unrelated to the procedure. Vascular imaging follow-up was available for 20 patients and the complete aneurysm occlusion rate was 95%., Conclusion: Flow-diversion could be a reasonably safe and effective technique for treating ruptured aneurysms in appropriately selected patients when conventional options of surgical clipping and coiling are considered challenging., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT., (© 2021 European Academy of Neurology.)

Background: Endovascular thrombectomy (ET) has transformed acute ischemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD, as measured by LV ejection fraction (LVEF), and clinical outcomes in patients with anterior cerebral circulation LVO who underwent ET., Methods: This multicenter retrospective cohort study examined anterior circulation LVO AIS patients from six international stroke centers. LVSD was measured by assessment of the echocardiographic LVEF using Simpson's biplane method of discs according to international guidelines. LVSD was defined as LVEF <50%. The primary outcome was defined as a good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3 months., Results: We included 440 AIS patients with LVO who underwent ET. On multivariate analyses, pre-existing diabetes mellitus (OR 2.05, 95% CI 1.24 to 3.39;p=0.005), unsuccessful reperfusion (Treatment in Cerebral Infarction (TICI) grade 0-2a) status (OR 4.21, 95% CI 2.04 to 8.66; p<0.001) and LVSD (OR 2.08, 95% CI 1.18 to 3.68; p=0.011) were independent predictors of poor functional outcomes at 3 months. On ordinal (shift) analyses, LVSD was associated with an unfavorable shift in the mRS outcomes (OR 2.32, 95% CI 1.52 to 3.53; p<0.001) after adjusting for age and ischemic heart disease., Conclusion: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to consider cardiac factors for ET, the degree of monitoring and prognostication post-procedure., Competing Interests: Competing interests: AM: Consultancy for Stryker, Phenox and Perflow. TA: Consultancy for Ablynx, Amnis Therapeutics, Anaconda, Cerenovus, Medtronic, Rapid Medical., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT., Methods: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03-1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72-0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99-1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87-1.46])., Conclusions: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Objective The objective of this article is to conduct a single-centre evaluation and quick literature review of the effectiveness of primary flow-diverter (FD) treatment of ruptured blood blister aneurysms (BBAs), with additional relevance of adjunctive coiling. Methods Patients presenting with subarachnoid haemorrhage (SAH) due to ruptured BBAs and subsequently treated with FDs were retrospectively selected from June 2010 to January 2017. Treatment techniques, angiographic data on occlusion rates and procedural success as well as clinical outcomes using the modified Rankin Scale (mRS) were collated. Cross-reference of results were made with available literature. Results Thirteen patients harbouring 14 BBAs were recruited. Of the 14 aneurysms, five (35.7%) showed immediate complete occlusion after the procedure (four of these five patients had adjunctive coiling). All of the aneurysms showed complete occlusion by the six- to nine-month control diagnostic angiogram. No rebleed or retreatment was experienced. Twelve of 13 (92%) patients had an mRS score of 0-1 at the last clinical follow-up. From the pooled data of the literature review, eventual aneurysm occlusion was achieved in 48/56 patients, with five patients requiring further endovascular treatment. In the clinical follow-up period, an mRS of 0-2 was recorded for 83.3% (45/54) of patients. Conclusion Endovascular reconstruction of BBAs using FD treatment is an effective method with good final clinical outcomes. Adjunctive use of coiling achieves higher incidence of immediate complete occlusion of BBAs.