CO2 delivery techniques in mini-sternotomy surgery and neurological events: a multicentric study.

BACKGROUND: The impact of air bubbles into the cerebral circulation after open heart surgery has been a topic of discussion since the introduction of the heart-lung machine. The aim of the study was to evaluate whether the use of a dedicated commercial sponge diffuser is better than a custom-made narrow section cannula or the absence of CO2 in preventing neurological events after aortic valve replacement via J mini-sternotomy. METHODS: Three cohorts of J-shaped mini-sternotomy performed at three different centers were prospectively compared: CO2 supplied via sponge diffuser, CO2 supplied via cannula, and no CO2 supply. Propensity matching was used to obtain comparable groups. The primary endpoints were postoperative stroke, transitory ischemic attack, convulsions, and dizziness. Secondary endpoints were 30-day mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: 275 patients were enrolled in the study. After propensity matching, the sponge diffuser cohort had a significantly lower duration of mechanical ventilation (P < 0.001) and 30-day mortality (P = 0.05) when compared to the cannula cohort and the no-CO2 cohort, a lower incidence of all neurological events (P = 0.03) and dizziness (P = 0.05) when compare to the no-CO2 cohort, and a lower intensive care unit length of stay when compared to the cannula cohort (P = 0.001). CONCLUSIONS: The sponge diffuser used to deliver the CO2 into the surgical field during aortic valve replacement via J mini-sternotomy has been demonstrated to guarantee better neurological outcomes compared to a custom-made narrow section cannula or the absence of CO2.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

The left atrial appendage closure by surgery 2 trial: statistical analysis plan for a randomized multicenter trial exploring if the closure of the left atrial appendage during open-heart surgery reduces stroke irrespective of patients' stroke risk and preoperative atrial fibrillation status.

BACKGROUND: Surgical left atrial appendage (LAA) closure concomitant to open-heart surgery prevents thromboembolism in high-risk patients. Nevertheless, high-level evidence does not exist for LAA closure performed in patients with any CHA2DS2-VASc score and preoperative atrial fibrillation or flutter (AF) status-the current trial attempts to provide such evidence. METHODS: The study is designed as a randomized, open-label, blinded outcome assessor, multicenter trial of adult patients undergoing first-time elective open-heart surgery. Patients with and without AF and any CHA2DS2-VASc score will be enrolled. The primary exclusion criteria are planned LAA closure, planned AF ablation, or ongoing endocarditis. Before randomization, a three-step stratification process will sort patients by site, surgery type, and preoperative or expected oral anticoagulation treatment. Patients will undergo balanced randomization (1:1) to LAA closure on top of the planned cardiac surgery or standard care. Block sizes vary from 8 to 16. Neurologists blinded to randomization will adjudicate the primary outcome of stroke, including transient ischemic attack (TIA). The secondary outcomes include a composite outcome of stroke, including TIA, and silent cerebral infarcts, an outcome of ischemic stroke, including TIA, and a composite outcome of stroke and all-cause mortality. LAA closure is expected to provide a 60% relative risk reduction. In total, 1500 patients will be randomized and followed for 2 years. DISCUSSION: The trial is expected to help form future guidelines within surgical LAA closure. This statistical analysis plan ensures transparency of analyses and limits potential reporting biases. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03724318. Registered 26 October 2018, https://clinicaltrials.gov/study/NCT03724318 . PROTOCOL VERSION: https://doi.org/10.1016/j.ahj.2023.06.003 .

Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.

[Preventive treatment to avoid recurrence of stroke and TIA is effective]. / Förebyggande behandling efter ischemisk stroke/TIA har effekt.

Healthy living with physical activity, healthy eating habits, no smoking, and no alcohol overuse have an important role in primary and secondary stroke prevention. Further secondary prevention depends on type and cause of stroke or TIA. After intracerebral bleeding, ischemic stroke or TIA, preventive pharmacological therapies include antihypertensive drugs. After ischemic stroke or TIA, treatment with antithrombotics (oral anticoagulants or antiplatelets) and statins is recommended. In stroke due to unusual causes, the pharmacological preventive treatment described above may need modification. For symptomatic carotid stenosis, carotid surgery is recommended, preferably within the first 14 days after onset. A surgical preventive treatment is closure of patent foramen ovale in patients aged 18-60 years with ischemic stroke of unknown cause.

[TIA - immediate acute care and treatment decrease the risk of stroke substantially]. / TIA ­ akut handläggning och behandling minskar strokerisk.

TIA is defined as an episode of neurological deficit with sudden onset, caused by focal cerebral or retinal ischemia lasting less than 24 hours. A tissue-based definition has been proposed but its application has been challenging, in part as its use requires magnetic resonance imaging. In most cases the diagnosis is solely based on history as provided by the patient. The diagnosis can therefore be challenging, and interobserver agreement between physicians is only fair. The importance of a TIA is its subsequent substantial risk of stroke, especially within the first weeks. Immediate acute care and treatment has been shown to decrease the risk of stroke substantially and is therefore crucial. Diagnostic procedures include imaging of the brain and neck vessels, ECG and cardiac rhythm monitoring, and blood pressure measuring. Treatment decisions are based on the diagnostic findings and include antithrombotic therapy, statins, blood pressure lowering medications, and carotid surgery if indicated.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines. METHODS: We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis. RESULTS: During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logeIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase logehsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]). CONCLUSIONS: Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.

Ninety-Day Stroke or Transient Ischemic Attack Recurrence in Patients Prescribed Anticoagulation in the Emergency Department With Atrial Fibrillation and a New Transient Ischemic Attack or Minor Stroke.

Background For patients with atrial fibrillation seen in the emergency department (ED) following a transient ischemic attack (TIA) or minor stroke, the impact of initiating oral anticoagulation immediately rather than deferring the decision to outpatient follow-up is unknown. Methods and Results We conducted a planned secondary data analysis of a prospective cohort of 11 507 adults in 13 Canadian EDs between 2006 and 2018. Patients were eligible if they were aged 18 years or older, with a final diagnosis of TIA or minor stroke with previously documented or newly diagnosed atrial fibrillation. The primary outcome was subsequent stroke, recurrent TIA, or all-cause mortality within 90 days of the index TIA diagnosis. Secondary outcomes included stroke, recurrent TIA, or death and rates of major bleeding. Of 11 507 subjects with TIA/minor stroke, atrial fibrillation was identified in 11.2% (1286, mean age, 77.3 [SD 11.1] years, 52.4% male). Over half (699; 54.4%) were already taking anticoagulation, 89 (6.9%) were newly prescribed anticoagulation in the ED. By 90 days, 4.0% of the atrial fibrillation cohort had experienced a subsequent stroke, 6.5% subsequent TIA, and 2.6% died. Results of a multivariable logistic regression indicate no association between prescribed anticoagulation in the ED and these 90-day outcomes (composite odds ratio, 1.37 [95% CI, 0.74-2.52]). Major bleeding was found in 5 patients, none of whom were in the ED-initiated anticoagulation group. Conclusions Initiating oral anticoagulation in the ED following new TIA was not associated with lower recurrence rates of neurovascular events or all-cause mortality in patients with atrial fibrillation.

Synchronous Carotid Endarterectomy and Anaortic Off-Pump Coronary Artery Bypass Surgery.

BACKGROUND: There is ongoing debate regarding the optimal strategy and timing for the surgical management of patients with severe concomitant carotid and coronary artery disease. Anaortic off-pump coronary artery bypass (anOPCAB), which avoids aortic manipulation and cardiopulmonary bypass, has been shown to reduce the risk of perioperative stroke. We present the outcomes of a series of synchronous carotid endarterectomy (CEA) and anOPCAB. METHODS: A retrospective review was performed. The primary endpoint was stroke at 30 days post-operation. Secondary endpoints included transient ischaemic attack, myocardial infarction and mortality 30 days post-operation. RESULTS: From 2009 to 2016, 1,041 patients underwent anOPCAB with a 30-day stroke rate of 0.4%. The majority of patients had preoperative carotid-subclavian duplex ultrasound screening and 39 were identified with significant concomitant carotid disease who underwent synchronous CEA-anOPCAB. The mean age was 71±7.5 years. Nine patients (23.1%) had previous neurological events. Thirty (30) patients (76.9%) underwent an urgent operation. For CEA, a conventional longitudinal carotid endarterectomy with patch angioplasty was performed in all patients. For anOPCAB, total arterial revascularisation rate was performed in 84.6% and the mean number of distal anastomoses was 2.9±0.7. In the 30-day postoperative period, there was one stroke (2.63%), two deaths (5.26%), two transient ischaemic attacks (TIAs) (5.26%) and no myocardial infarction. Two patients experienced acute kidney injury (5.26%), one of which required haemodialysis (2.63%). Mean length of stay was 11.37±7.9 days. CONCLUSION: Synchronous CEA and anOPCAB is a safe and effective option for patients' severe concomitant disease. Preoperative carotid-subclavian ultrasound screening allows identification of these patients.

Cost-Effectiveness of Smoking Cessation Interventions in Patients With Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population. METHODS: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty. RESULTS: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs. CONCLUSIONS: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Direct Ischemic Postconditioning After Carotid Endarterectomy in the Prevention of Postoperative Cerebral Ischemic Complications-Observational Case-Control Study.

INTRODUCTION: Ischemic postconditioning (IPCT) represents one of the several therapeutic strategies to attenuate ischemic reperfusion injury (IR) after carotid endarterectomy (CEA). We here present the first in-human study of IPCT in carotid surgery. METHODS: The study represents an observational case-control study, with the data collected in our Institution carotid database. From December 2015 to December 2020, a total of 300 patients were included in our study; IPCT group consisted of 148 patients in whom ischemic postconditioning was performed while control group consisted of 152 patients in whom IPCT was not performed. Indications for IPCT technique were: severe unilateral internal carotid artery (ICA) stenosis (>90%), severe bilateral ICA stenosis (>80%), severe ICA stenosis (>80%) with contralateral ICA occlusion and ICA subocclusion. IPCT was performed by applying 6 cycles of 30 sec reperfusion (declamping of ICA)/30 sec ischemia (clamping of ICA) after finishing the procedure and initial declamping. Two groups of patients were compared in terms of occurrence of intrahospital and early postoperative stroke, TIA (transient ischemic attack) and neurologic morbidity. RESULTS: Cumulative incidence of intrahospital postoperative stroke or TIA was significantly higher in the control group (5.3% vs 0.7%, P = .036). According to carotid plaque characteristics, patients in the IPCT group had significantly more frequent presence of heterogenous plaque, as well as ulcerated plaque, which was associated with the absence of postoperative stroke and significantly lower cumulative rate of TIA/stroke when compared to the control group (43.9% vs 8% and 47.3% vs 1.5%). During the follow-up period of 1 month after the surgery, there were no cases of stroke, TIA and deaths due to neurological causes in both groups of patients. CONCLUSION: Our results showed that IPCT significantly reduced the incidence of postoperative cerebral ischemic complications after CEA in high-risk patients for IR injury when compared to the control group.

Nontraditional Risk Factors for Residual Recurrence Risk in Patients with Ischemic Stroke of Different Etiologies.

BACKGROUND AND OBJECTIVE: With the popularization of guideline-based secondary prevention based on traditional risk factors, rates of stroke recurrence reduced greatly after ischemic stroke (IS) or transient ischemic attack (TIA), but the residual risk still exists. We aim to evaluate which IS subtype benefits the most from the current secondary prevention and to evaluate nontraditional risk factors for residual recurrence risk of different IS etiologies. METHODS: The study included IS/TIA patients who participated in both biomarker substudy and imaging substudy of the Third China National Stroke Registry. We used 5 guideline-recommended interventions (antiplatelet, statins, anticoagulant, antihypertensive, and antidiabetic therapies) to document the performance of secondary prevention care. Residual risk was defined as the risk of stroke recurrence despite adherence to these 5 guideline-based secondary prevention strategies. Risk factors associated with stroke recurrence were analyzed by using Cox regression models. RESULTS: In total, 9,733 patients were included in this study. At 3 months, 4,186 (43.0%) patients adhered to 5 secondary prevention strategies, and the residual risk of recurrence was 5.1%. According to Trial of Org 10172 in Acute Stroke Treatment subtypes, cardioembolism benefited the most from current secondary prevention (relative risk reduction: 65.2%), followed by large-artery atherosclerosis (LAA) (29.0%) and small-artery occlusion (SAO) (20.0%). Despite adhering to secondary prevention strategies, high sensitivity C-reactive protein, interleukin-6 (IL-6) levels, and impaired renal function were independent risk factors for the residual recurrence risk of LAA subtype, while IL-6 and trimethylamine N-oxide significantly contributed to the residual risk of SAO subtype. CONCLUSIONS: LAA and SAO subtypes own the specific nontraditional risk factors while inflammation is a common risk factor for residual recurrence risk of both.

Editor's Choice - Peri-Operative Outcomes of Carotid Endarterectomy are Not Improved on Dual Antiplatelet Therapy vs. Aspirin Monotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis of the peri-operative outcomes of carotid endarterectomy (CEA) on dual antiplatelet therapy (DAPT) vs. aspirin monotherapy was carried out, to determine optimal peri-operative management with these antiplatelet agents. DATA SOURCES: The Web of Science, Pubmed, and Embase databases were searched from inception to July 2021. The corresponding authors of excluded articles were contacted to obtain additional data for possible inclusion. REVIEW METHODS: The main outcomes included ischaemic complications (stroke, transient ischaemic attack [TIA], and transcranial Doppler [TCD] measured micro-emboli), haemorrhagic complications (haemorrhagic stroke, neck haematoma, and re-operation for bleeding), and composite outcomes. Pooled estimates using odds ratios (ORs) were combined using a random or fixed effects model based on the results of the chi square test and calculation of I2. RESULTS: In total, 47 411 patients were included in 11 studies, with 14 345 (30.2%) receiving DAPT and 33 066 (69.7%) receiving aspirin only. There was no significant difference in the rates of peri-operative stroke (OR 0.87, 95% confidence interval [CI] 0.72 - 1.05) and TIA (OR 0.78, 95% CI 0.52 - 1.17) despite a significant reduction in TCD measured micro-emboli (OR 0.19, 95% CI 0.10 - 0.35) in the DAPT compared with the aspirin monotherapy group. Subgroup analysis did not reveal any significant difference in ischaemic stroke risk between patients with asymptomatic and symptomatic carotid artery stenosis. DAPT was associated with an increased risk of neck haematoma (OR 2.79, 95% CI 1.87 - 4.18) and re-operation for bleeding (OR 1.98, 95% CI 1.77 - 2.23) vs. aspirin. Haemorrhagic stroke was an under reported outcome in the literature. CONCLUSION: This meta-analysis found that CEA while on DAPT increased the risk of haemorrhagic complications, with similar rates of ischaemic complications, vs. aspirin monotherapy. This suggests that the risks of performing CEA on DAPT outweigh the benefits, even in patients with symptomatic carotid stenosis. The overall quality of studies was low, and improved reporting of CEA outcomes in the literature is necessary.

Systemic administration of sunflower oil exerts neuroprotection in a mouse model of transient focal cerebral ischaemia.

OBJECTIVES: Natural products are valuable sources of nutraceuticals for the prevention or treatment of ischemic stroke, a major cause of death and severe disability worldwide. Among the mechanisms implicated in cerebral ischemia-reperfusion damage, oxidative stress exerts a pivotal role in disease progression. Given the high antioxidant potential of most components of sunflower oil, we have explored its effects on ischemic brain injury produced in the mouse by transient occlusion of the middle cerebral artery (MCAo). KEY FINDINGS: Intraperitoneal (i.p.) administration of sunflower oil at doses of 3 ml/kg (48 h, 24 h and 1 h before MCAo) significantly reduced brain infarct volume and oedema assessed 24 h after the insult. This neuroprotective treatment schedule also prevented the elevation of brain lipid peroxidation produced by MCAo-reperfusion injury. By contrast, doses of 0.03 ml/kg of sunflower oil resulted ineffective on both cerebral damage and lipid peroxidation. Although sunflower oil did not affect serum levels of Diacron-reactive oxygen metabolites (d-ROMs), both 0.03 and 3 ml/kg dosing regimens resulted in the preservation of serum biological antioxidant potential (BAP) that was otherwise dramatically reduced 24 h after MCAo. CONCLUSIONS: Sunflower oil represents a promising source of neuroprotective extracts/compounds that can be exploited for the prevention and/or treatment of cerebral ischemia.

Canadian Stroke Best Practice Recommendations: Secondary Prevention of Stroke Update 2020.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity.

Evidence for the clinical use of neuroprotective drugs for the treatment of cerebral ischemia (CI) is still greatly limited. Spatial/temporal disorientation and cognitive dysfunction are among the most prominent long-term sequelae of CI. Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa that exerts neuroprotective effects against experimental CI. The present study investigated possible neuroprotective mechanisms of action of CBD on spatial memory impairments that are caused by transient global cerebral ischemia (TGCI) in rats. Hippocampal synaptic plasticity is a fundamental mechanism of learning and memory. Thus, we also evaluated the impact of CBD on neuroplastic changes in the hippocampus after TGCI. Wistar rats were trained to learn an eight-arm aversive radial maze (AvRM) task and underwent either sham or TGCI surgery. The animals received vehicle or 10 mg/kg CBD (i.p.) 30 min before surgery, 3 h after surgery, and then once daily for 14 days. On days 7 and 14, we performed a retention memory test. Another group of rats that received the same pharmacological treatment was tested in the object location test (OLT). Brains were removed and processed to assess neuronal degeneration, synaptic protein levels, and dendritic remodeling in the hippocampus. Cannabidiol treatment attenuated ischemia-induced memory deficits. In rats that were subjected to TGCI, CBD attenuated hippocampal CA1 neurodegeneration and increased brain-derived neurotrophic factor levels. Additionally, CBD protected neurons against the deleterious effects of TGCI on dendritic spine number and the length of dendritic arborization. These results suggest that the neuroprotective effects of CBD against TGCI-induced memory impairments involve changes in synaptic plasticity in the hippocampus.

Rates, Predictors, and Impact of Smoking Cessation after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

BACKGROUND: Smoking cessation after a first cardiovascular event reduces the risk of recurrent vascular events and mortality. This systematic review and meta-analysis aimed to summarize data on the rates, predictors, and the impact of smoking cessation in patients after a stroke or transient ischemic attack (TIA). METHODS: MEDLINE, EMBASE and Web of Science were searched to identify all published studies providing relevant data through May 20, 2021. Random-effects meta-analysis method was used to pool proportions. Some findings were summarized narratively. RESULTS: Twenty-five studies were included. The pooled smoking cessation rates were 51.0% (8 studies, n = 1738) at 3 months, 44.4% (7 studies, n = 1920) at 6 months, 43.7% (12 studies, n = 1604) at 12 months, and 49.8% (8 studies, n = 2549) at 24 months or more of follow-up. Increased disability and intensive smoking cessation support programs were associated with a higher likelihood of smoking cessation, whereas alcohol consumption and depression had an inverse effect. Two studies showed that patients who quit smoking after a stroke or a TIA had substantially lower risk of recurrent stroke, death, and a composite of stroke, myocardial infarction, and death. CONCLUSION: Smoking cessation in stroke survivors is associated with reduced recurrent vascular events and death. About half of smokers who experience a stroke or a TIA stop smoking afterwards. Those with low post-stroke disability, who consume alcohol, or have depression are less likely to quit. Intensive support programs can increase the likelihood of smoking cessation.

Synthesis and biological evaluation of 1,2,4-oxadiazole core derivatives as potential neuroprotectants against acute ischemic stroke.

Here, we report the synthesis and neuroprotective capacity of 27 compounds with a bisphenol hydroxyl-substituted 1,2,4-triazole core or 1,2,4-oxadiazole core for stroke therapy. In vitro studies of the neuroprotective effects of compounds 1-27 on sodium nitroprusside (SNP)-induced apoptosis in PC12 cells indicate that compound 24 is the most effective compound conferring potent protection against oxidative injury. Compound 24 inhibits reactive oxygen species (ROS） accumulation and restores the mitochondrial membrane potential (MMP). Moreover, further analysis of the mechanism showed that compound 24 activates the antioxidant defence system by promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increasing the expression of haem oxygenase 1 (HO-1). An in vivo study was performed in a rat model of transient focal cerebral ischaemia generated by the intraluminal occlusion of the middle cerebral artery (MCAO). Compound 24 significantly reduced brain infarction and improved neurological function. Overall, compound 24 potentially represents a promising compound for the treatment of stroke.

The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients.

The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.

Carotid Endarterectomy: A Single Institutional Experience of 28 Years From Pakistan.

BACKGROUND: Cerebrovascular event is the most common reason of acute neurological injury in the western world. There is an extensive literature and data available on its prognosis, outcomes and complications rates from the west, yet still, data regarding its safety and efficacy is scarce from the South Asian belt. OBJECTIVE: To elucidate the role of carotid endarterectomy in patients with carotid stenosis regarding prevention of stroke and safety of the procedure. METHODS: A descriptive case series of 335 consecutive patients from January 1990 till July 2018. All patients who underwent carotid endarterectomy were included. Patient having asymptomatic carotid disease (≥90%), history of a transient ischemic attack or patients with a recent or previous episode of ischemic stroke (≥60%) were selected for the procedure. All procedures were performed under GA. Post operatively patients were kept on antiplatelet therapy and followed on outpatient basis for any complications using carotid duplex scans. Data regarding 30-day postoperative parameters of the procedure were collected and evaluated. P< 0.05 is considered significant. RESULTS: A total of 335 carotid endarterectomies were performed. The majority of patients in our series were males 68.90% (n = 230) compared to 31.10% (n = 105) females (P< 0.05). There were no intraoperative mortalities in our patients. The 15-day perioperative mortality was 1.5% (n = 5), out of which 3 patients had concomitant CABG and died of cardiac complications. The mortality rate of CEA alone was 0.6% (n = 2). Six patients (1.8%) developed focal neurological deficits in the postoperative period during the hospital stay. Three patients developed wound infection after surgery. Neck hematoma formation occurred in 11.7% (n = 39) patients and 7 required immediate decompression. A total of 321 patients remained stroke free at 6 months follow up. There was no increased risk of stroke secondary to bilateral carotid disease (OR 1.9 CI 0.35-10.7 P= 0.44). CONCLUSION: Carotid Endarterectomy is a relatively safe and effective procedure in our large series from Pakistan. It remains the standard for management of carotid stenosis in symptomatic as well as asymptomatic patients with critical stenosis.