Time to Benefit and Harm of Direct Oral Anticoagulants in Device-Detected Atrial Fibrillation: A Pooled Analysis of the NOAH-AFNET 6 and ARTESiA Trials.

BACKGROUND: Direct oral anticoagulants (DOACs) reduce stroke risk in patients with device-detected atrial fibrillation (DD-AFib) but increase major bleeding risk. The time to benefit (TTB) and time to harm (TTH) are not well quantified. OBJECTIVE: To determine TTB and TTH in DOACs-treated DD-AFib patients. METHODS: Studies were identified from PubMed searching until November 2023. The primary efficacy outcome was the time to first stroke event, and the primary safety outcome was the time to the first major bleeding event. Pooled hazard ratio (HR) and its confidence interval (CI) were calculated through reconstructed patient-level data and study-level data. Weibull model and Markov chain Monte Carlo simulation were applied to determine time to specific absolute risk change thresholds. RESULTS: Two trials involving DOACs, NOAH-AFNET 6 and ARTESiA, were identified, which randomized 6,548 adults with mean age over 75 and a median atrial high-rate episode duration ranging from 1.5 to 2.8 hours. DOACs decreased the risk of stroke (HR 0.67, 95% CI: 0.50 to 0.90) but increased the risk of major bleeding (HR 1.57, 95% CI: 1.21 to 2.04). A TTB of 2.67 years was needed to prevent one stroke per 100 DOACs-treated patients, while a TTH of 1.67 years was needed to observe one major bleeding. CONCLUSIONS: In elderly patients with low durations of DD-AFib, DOACs result in a delayed and restricted stroke-preventive benefit while posing an early-onset bleeding risk. Our findings offer new insights into the risk-benefit profile and provide clinicians an additional dimension to facilitate shared decision-making discussions with patients.

Machine Learning Modeling to Predict Atrial Fibrillation Detection in Embolic Stroke of Undetermined Source Patients.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. OBJECTIVE: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. METHODS: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. RESULTS: The median age of the cohort was 67 (IQR 59-74) years old and the median monitoring duration was 1051 (IQR 478-1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736-0.737, multilayer perceptron with an AUC of 0.697-0.708, XGBoost with an AUC of 0.697-0.697, and random forest with an AUC of 0.663-0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. CONCLUSION: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy.

Patent foramen ovale closure in ischemic stroke patients with and without thrombophilia: a systematic review and meta-analyses.

Ischemic stroke patients with thrombophilia and patient foramen ovale (PFO) may have an increased risk of recurrent stroke and transient ischemic attack (TIA), and may benefit from PFO closure. However, screening for thrombophilia is not routinely performed and the impact of thrombophilia on prognosis after PFO closure is uncertain. We aim to compare the risk of recurrent stroke and TIA after PFO closure in patients with thrombophilia versus those without. We performed a systematic review and meta-analyses of the literature, with a comprehensive literature search performed on 12 January 2023. Studies comparing the outcomes of patients with and without thrombophilia after PFO closure were included. The primary outcome evaluated was a recurrence of acute cerebrovascular event (ACE), a composite of recurrent ischemic stroke and recurrent TIA. The secondary outcomes included recurrent ischemic stroke only or TIA only. A total of 8 cohort studies were included, with a total of 3514 patients. There was an increased risk of stroke/TIA in patients with thrombophilia compared to those without thrombophilia after PFO (OR: 1.42, 95% CI: 1.01-1.99, I2 = 50%). The association between risk of TIA only (OR: 1.36, 95% CI: 0.77-2.41, I2 = 0%) and stroke only (OR: 1.09, 95% CI: 0.54-2.21, I2 = 0%) with thrombophilia did not reach statistical significance. There is an increased risk of recurrent cerebral ischemia event in patients with thrombophilia compared to those without thrombophilia after PFO closure. Future large prospective studies are necessary to characterise the risk and benefits of PFO closure, as well as the appropriate medical treatment to reduce the risk of recurrent stroke and TIA in this high-risk population.

Prehospital stroke care in Singapore.

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Sonothrombolysis for Ischemic Stroke.

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

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.

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation.

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.

Dual Antiplatelet Therapy for the Acute Management and Long-term Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack, An Updated Review.

To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For minor ischemic stroke and high-risk transient ischemic attack, the aspirin-clopidogrel combination is now recommended for acute short-term treatment, whereas aspirin-ticagrelor combination may be considered in selected patients, especially those with resistance to clopidogrel. For long-term stroke prevention, aspirin-dipyridamole combination has been used as an alternative to antiplatelet monotherapy, and aspirin or clopidogrel combined with cilostazole may be prescribed for added protection in high-risk patients. In this paper, we review the development of DAPT from a historical perspective and describe the findings from major clinical trials published up until the end of 2023. Using the 2021 American Heart Association guideline for secondary stroke prevention as a basis for our recommendations, we further discuss areas of controversy and more recent developments to provide an updated review for clinicians to consider in their daily practice.

Comparing the Impact of Stenting vs. Medical Therapy for Intracranial Arterial Stenosis : A Systematic Review and One-stage and Two-stage Meta-Analysis of Randomized Clinical Trials.

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], I²â€¯= 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41-66.45], I²â€¯= 0%) and death (RR = 5.41 [1.20-24.28], I²â€¯= 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.

Effect of anesthetic strategies on distal stroke thrombectomy in the anterior and posterior cerebral artery.

BACKGROUND: Numerous questions regarding procedural details of distal stroke thrombectomy remain unanswered. This study assesses the effect of anesthetic strategies on procedural, clinical and safety outcomes following thrombectomy for distal medium vessel occlusions (DMVOs). METHODS: Patients with isolated DMVO stroke from the TOPMOST registry were analyzed with regard to anesthetic strategies (ie, conscious sedation (CS), local (LA) or general anesthesia (GA)). Occlusions were in the P2/P3 or A2-A4 segments of the posterior and anterior cerebral arteries (PCA and ACA), respectively. The primary endpoint was the rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3) and the secondary endpoint was the rate of modified Rankin Scale score 0-1. Safety endpoints were the occurrence of symptomatic intracranial hemorrhage and mortality. RESULTS: Overall, 233 patients were included. The median age was 75 years (range 64-82), 50.6% (n=118) were female, and the baseline National Institutes of Health Stroke Scale score was 8 (IQR 4-12). DMVOs were in the PCA in 59.7% (n=139) and in the ACA in 40.3% (n=94). Thrombectomy was performed under LA±CS (51.1%, n=119) and GA (48.9%, n=114). Complete reperfusion was reached in 73.9% (n=88) and 71.9% (n=82) in the LA±CS and GA groups, respectively (P=0.729). In subgroup analysis, thrombectomy for ACA DMVO favored GA over LA±CS (aOR 3.07, 95% CI 1.24 to 7.57, P=0.015). Rates of secondary and safety outcomes were similar in the LA±CS and GA groups. CONCLUSION: LA±CS compared with GA resulted in similar reperfusion rates after thrombectomy for DMVO stroke of the ACA and PCA. GA may facilitate achieving complete reperfusion in DMVO stroke of the ACA. Safety and functional long-term outcomes were comparable in both groups.

First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: An analysis of an international multicenter study.

INTRODUCTION: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. PATIENTS AND METHODS: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months. RESULTS: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively. CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Prognostication of Outcomes in Spontaneous Intracerebral Hemorrhage: A Propensity Score-Matched Analysis with Support Vector Machine.

OBJECTIVE: The role of surgery in spontaneous intracerebral hemorrhage (SICH) remains controversial. We aimed to use explainable machine learning (ML) combined with propensity-score matching to investigate the effects of surgery and identify subgroups of patients with SICH who may benefit from surgery in an interpretable fashion. METHODS: We conducted a retrospective study of a cohort of 282 patients aged ≥21 years with SICH. ML models were developed to separately predict for surgery and surgical evacuation. SHapley Additive exPlanations (SHAP) values were calculated to interpret the predictions made by ML models. Propensity-score matching was performed to estimate the effect of surgery and surgical evacuation on 90-day poor functional outcomes (PFO). RESULTS: Ninety-two patients (32.6%) underwent surgery, and 57 patients (20.2%) underwent surgical evacuation. A total of 177 patients (62.8%) had 90-day PFO. The support vector machine achieved a c-statistic of 0.915 when predicting 90-day PFO for patients who underwent surgery and a c-statistic of 0.981 for patients who underwent surgical evacuation. The SHAP scores for the top 5 features were Glasgow Coma Scale score (0.367), age (0.214), volume of hematoma (0.258), location of hematoma (0.195), and ventricular extension (0.164). Surgery, but not surgical evacuation of the hematoma, was significantly associated with improved mortality at 90-day follow-up (odds ratio, 0.26; 95% confidence interval, 0.10-0.67; P = 0.006). CONCLUSIONS: Explainable ML approaches could elucidate how ML models predict outcomes in SICH and identify subgroups of patients who respond to surgery. Future research in SICH should focus on an explainable ML-based approach that can identify subgroups of patients who may benefit functionally from surgical intervention.

Prevalence and Associations of Cognitive Impairment in Adult Patients with Moyamoya Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment, and in the long term Alzheimer's disease, vascular, or mixed dementia, are potential complications of moyamoya disease (MMD), of which the prevalence and associations are not well established. OBJECTIVE: We performed a systematic review and meta-analysis to investigate the prevalence of cognitive impairment in adult patients with MMD as well as its clinical and demographic correlates. METHODS: We performed a systematic search of four electronic databases: PubMed (MEDLINE), EMBASE, Scopus, and Cochrane Library, profiling studies from inception until 7 May 2023. Clinical data consisting of population characteristics, comorbidities, cognitive assessment tools used, and prevalence of cognitive impairment was extracted. RESULTS: Seventeen studies were included in the meta-analysis, with a total study population of 1,190 patients. All studies assessed cognition, and the overall prevalence of cognitive impairment in MMD patients was 54.59%. A subgroup analysis identified that the prevalence of executive dysfunction in MMD patients was 31.55%. We performed a meta-regression analysis which identified that cognitive impairment was not associated with age, education level, or a history of ischemic or hemorrhagic stroke. CONCLUSIONS: A substantial proportion of MMD patients have cognitive impairment, and cognitive impairment was found to have no association with a history of stroke. Further research is necessary to investigate the longitudinal relationship of MMD and cognitive impairment, and the impact of bypass surgery on cognitive impairment.

Revolutionizing the Management of Large-Core Ischaemic Strokes: Decoding the Success of Endovascular Therapy in the Recent Stroke Trials.

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.

Comparison of short-term outcomes between patients with extracranial carotid and/or intracranial atherosclerotic disease.

OBJECTIVE: To directly compare the 90-day outcomes of patients with symptomatic intracranial atherosclerotic disease (ICAD), extracranial carotid atherosclerotic disease (ECAD), and ICAD with concomitant ECAD. METHODS: From 2017-2021, patients who had (1) a transient ischemic attack or ischemic stroke within 30 days of admission as evaluated by a stroke neurologist and (2) ipsilateral ICAD and/or ECAD were prospectively enrolled. The cohort was divided into three groups: ICAD, ECAD, and ICAD with concomitant ECAD. The primary outcome assessed was 90-day ischemic stroke recurrence. Secondary outcomes included 90-day myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE, including cardiovascular death, nonfatal MI, and/or nonfatal ischemic stroke). RESULTS: Of 371 patients included in the analysis, 240 (64.7%) patients had ICAD only, 93 (25.0%) patients had ECAD only, and 38 (10.3%) patients had ICAD with concomitant ECAD. On multivariate time-to-event analysis adjusting for potential confounders and with ICAD as the reference comparator, the risk of 90-day clinical outcomes was highest among patients with ICAD and concomitant ECAD, with adjusted hazard ratios of 4.54 (95% CI=1.45, 14.2; p = 0.006), 9.32 (95% CI=1.58, 54.8; p = 0.014), and 8.52 (95% CI=3.54, 20.5; p < 0.001) for 90-day ischemic stroke, MI, and MACE, respectively. CONCLUSIONS: Patients with ICAD and concomitant ECAD have a poorer prognosis and are at significantly higher risk for 90-day ischemic stroke, MI, and MACE. Further research should focus on the evaluation of coronary atherosclerotic disease and more intensive medical therapy in this population.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.