Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy i...Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy in the short-term treatment of various cognitive impairments.This study evaluated the efficacy of butylphthalide in preventing cognitive decline over a 12-month period in patients with ischaemic stroke.Methods This prospective following-up study involved patients newly diagnosed with ischaemic stroke between 1 month and 6 months after stroke onset and not in the acute phase.Patients were assigned to either the butylphthalide or control group.Cognitive function was assessed using the mini-mental state examination(MMSE)at baseline and at the 12-month follow-up.Statistical analyses included t-tests,χ2 tests and multivariate regression analyses.Results Butylphthalide was negatively associated with the MMSE D-value(β=−0.122;95%CI−1.932 to−0.298;p=0.003)and the MMSE D-value percentage(β=−0.117;95%CI−0.057 to−0.011;p=0.004).A multivariate analysis indicated that butylphthalide treatment was negatively associated with both changes in orientation and language score.Additionally,the incidence of cognitive decline was significantly lower in the butylphthalide group(OR,0.612;p=0.020)than the control group.An age of≥60 years and lower educational level were identified as risk factors for lower cognitive score and cognitive decline.Conclusion This study demonstrated that butylphthalide is effective in preventing cognitive decline in patients with ischaemic stroke.These findings have significant implications for clinical practice,suggesting that butylphthalide could be incorporated into standard post-stroke care regimens to improve patient outcomes and reduce the healthcare burden.Additional multicentre double-blind trials are recommended to confirm these results in diverse populations.展开更多
Rationale Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke(AIS).Preclinical research indicates that tocilizumab,an interleukin-6 receptor antagonist,can atten...Rationale Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke(AIS).Preclinical research indicates that tocilizumab,an interleukin-6 receptor antagonist,can attenuate ischaemia-reperfusion damage by exerting anti-inflammatory and neuroprotective effects.Aim To determine tocilizumab’s efficacy and safety when combined with endovascular thrombectomy(EVT)in patients with acute anterior circulation large vessel occlusion(LVO).Sample size estimates To determine a 30%decrease in average infarct core volume comparing the intervention and historical control groups(mean increase of 18.7 mL(SD=9.7 mL)post-thrombectomy)via a two-sided test(alpha=0.05,power=80%),accounting for a 10%drop-out rate,we plan to recruit 108 participants.Methods and design This trial is designed as a randomised,multicentre,double-blind,placebo-controlled trial.Patients will be randomly and evenly allocated to the tocilizumab or placebo groups.Study outcomes The primary endpoint is the change in infarct core volume between baseline and 72 hours post-treatment.Secondary outcomes include the 90-day modified Rankin scale score(0–2,indicating functional independence).The key safety endpoints include 90-day mortality and symptomatic intracerebral haemorrhage within 72 hours after EVT.Discussion Administering tocilizumab within 24 hours of stroke as an adjunct to EVT may effectively reduce the infarct core volume for patients experiencing AIS with anterior circulation LVO,potentially improving functional outcomes in these patients.展开更多
Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As ea...Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As each year less than 1%of eligible patients receive this therapy worldwide,efficacious new therapeutics are desperately needed.Emerging evidence suggest endothelial progenitor cells(EPCs),capable of repairing damaged vasculature,as one such therapeutics.However,questions regarding their optimal dose,delivery route and in vivo survivability remain largely unanswered.Outgrowth endothelial cells,generated in large numbers by ex vivo expansion of EPCs,enable effective assessment of these issues and may eventually serve as off-the-shelf therapeutics.Correlations between circulating EPC levels and stroke outcome imply that EPCs may also serve as clinical biomarkers for stroke.This viewpoint briefly evaluates the current evidence,pinpoints the gaps in the literature and proposes new directions for research.展开更多
Ischaemic stroke is one of the commonest causes of morbidity and mortality worldwide and around a fifth of events can be attributed to a cardioembolic source. This is typically due to atrial fibrillation(AF), the most...Ischaemic stroke is one of the commonest causes of morbidity and mortality worldwide and around a fifth of events can be attributed to a cardioembolic source. This is typically due to atrial fibrillation(AF), the most common sustained cardiac arrhythmia. However, AF can, at times, be difficult to detect due to a relative lack of symptoms and the fact that it can be paroxysmal in nature. Studies have shown that diagnosis of AF improves as the length of cardiac monitoring increases. However, prolonged cardiac monitoring is not a costeffective way of diagnosing AF. Therefore, an alternative approach may be to empirically anticoagulate individuals who are at high risk of stroke. This article summarises current evidence surrounding stroke risk prediction, the use of anticoagulation in the secondary prevention of stroke and its use in the primary prevention of stroke in high risk groups with the aim of determining whether empirical anticoagulation is a safe and effective strategy.展开更多
Objective:To screen risk factors for epilepsy after acute ischaemic stroke based on meta-analysis and cohort study and to establish a predictive model.Methods:Computer searches of MEDLINE,Embase,Cochrane library,Web o...Objective:To screen risk factors for epilepsy after acute ischaemic stroke based on meta-analysis and cohort study and to establish a predictive model.Methods:Computer searches of MEDLINE,Embase,Cochrane library,Web of Scinence,PubMed,CNKI,and WanFang Data data were conducted to collect literature on epilepsy after in acute ischemic stroke,from database creation to September 1,2022.The RRs and their 95%confidence intervals(CI)for risk factors for post stroke epilepsy were extracted for each study,and pooled estimates of the RRs and 95%CIs for each study were generated using either a random-effects model or a fixed-effects model.Beta coefficients for each risk factor were calculated based on the combined RR and their corresponding 95%CIs.The beta coefficients were multiplied by 10 and rounded.Results:Ten articles were identified for final inclusion in this meta-analysis,with a total of 141948 cases and 3702 cases of post stroke epilepsy.The risk factors included in the final risk prediction model were infarct size(RR 4.67,95%CI 1.41~15.47;P=0.01),stroke recuRRence(RR 2.48,95%CI 2.01~3.05;P<0.00001),stroke etiology(RR 1.70,95%CI 1.34~2.15;P<0.00001),stroke severity(RR 1.70,95%CI 1.34~2.15;P<0.00001),and stroke risk.stroke severity(RR 1.53,95%CI 1.39~1.70;P<0.00001),NIHSS score(RR 2.91,95%CI 1.64~5.61;P=0.0003),early-onset epilepsy(RR 5.62,95%CI 5.08~6.22;P<0.00001),cortical lesions(RR 3.83.95%CI 2.23~6.58;P<0.00001),total anterior circulation infarction(RR 18.94,95%CI 10.38~34.57;P<0.00001),partial anterior circulation infarction(RR 4.39,95%CI 2.29~8.40;P<0.00001),cardiovascular events(RR 1.78,95%CI 1.59~1.99;P<0.00001).Conclusion:Based on a systematic review and meta-analysis,we developed a simple risk prediction model for late epilepsy in baseline ischemic stroke that integrates clinical risk factors,including infarct size,stroke recurrence,stroke etiology,stroke severity,NIHSS score,early onset epilepsy,cortical lesions,stroke subtype,and cardiovascular events.展开更多
<strong>Introduction:</strong> Ischemic strokes represent a classic complication of infective endocarditis (IE) and are most often related to the fragmentation of valvular vegetation. In most cases, they o...<strong>Introduction:</strong> Ischemic strokes represent a classic complication of infective endocarditis (IE) and are most often related to the fragmentation of valvular vegetation. In most cases, they occur in the Sylvian territory and are related to<em> Staphylococcus aureus</em>. MRI can demonstrate, in addition to the AVCI image, cerebral microbleeds (CMBs) that are very suggestive of the diagnosis. We present the case of a patient who presented an ischemic stroke occurring in the context of infective endocarditis.<strong> Observation:</strong> A 32-year-old woman with no previous medical history initially presented with acute febrile headache, two weeks later she developed right hemiplegia with aphasia in the context of fever. Her general examination revealed lesions on the soles of her feet, in the form of nodules, infected in places, suggestive of Janeway nodules (characteristic of IE). The brain MRI showed an ischemic stroke in the Sylvian territory, with the presence of multiple microbleeds on the magnetic susceptibility sequences. The biological examination showed a severe inflammatory syndrome;the transthoracic echocardiography (TTE) confirmed the presence of vegetation on the aortic valve;and the blood cultures showed a <em>Staphylococcus aureus</em>. Antibiotic therapy was started, and the patient was transferred to the cardiology department. <strong>Discussion: </strong>Our observation has a double interest. The first is clinical due to the presence of plantar nodules (Janeway’s nodules) that are characteristic of IE which should orientate the diagnosis before the installation of the stroke, and the second is radiological and linked to the discovery of microbleeds. Their presence is increasingly reported in the literature, but their pathophysiology is not yet very clear. <strong>Conclusion:</strong> Stroke is the most frequent extracardiac complication during IE. The presence of microbleeds contributes to early diagnosis, especially in asymptomatic forms.展开更多
Background Whether mean arterial pressure(MAP)and pulse pressure(PP),two indicators of cerebral perfusion,could guide the selection of anti-hypertensive strategies after acute ischaemic stroke remains uncertain.Our st...Background Whether mean arterial pressure(MAP)and pulse pressure(PP),two indicators of cerebral perfusion,could guide the selection of anti-hypertensive strategies after acute ischaemic stroke remains uncertain.Our study was to explore the impact of early anti-hypertensive intervention on adverse clinical outcomes following ischaemic stroke stratified by the levels of MAP and PP based on the China Antihypertensive Trial in Acute Ischemic Stroke(CATIS).Methods The trial randomised 4071 acute ischaemic stroke patients with elevated systolic blood pressure(SBP)to receive anti-hypertensive treatment(targeting a 10%-25%reduction in SBP during the 24 hours postrandomisation,reaching a BP level<140/90 mm Hg in 7 days,further keeping these levels throughout hospitalisation)or discontinue anti-hypertensive treatment during hospitalisation.The primary outcome was death or major disability at 14 days or hospital discharge.Study outcomes were analysed by comparing the BP-lowering intervention group and control group,stratified by tertiles of MAP or PP levels.Results No significant difference was observed in the primary outcome between the intervention and control groups across all MAP(p=0.69 for homogeneity)and PP(p=0.78 for homogeneity)categories.The corresponding odds ratios(95%CIs)were 1.08(0.85-1.36),0.92(0.74-1.15)and 1.00(0.81-1.25)for participants with low,intermediate,and high MAP and were 0.99(0.79-1.25),1.06(0.84-1.34)and 0.95(0.77-1.18)for participants in PP subgroups,respectively.Furthermore,early anti-hypertensive intervention was not associated with secondary outcomes(including neurological deterioration,recurrent stroke,vascular events and all-cause mortality)by MAP and PP(all p>0.05).Conclusions Early anti-hypertensive therapy neither decreased nor increased the odds of major disability,mortality,recurrent stroke or vascular events in patients with acute ischaemic stroke regardless of different MAP and PP levels.展开更多
Background CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed.Machine learning techniques can provide rapid automated CT assessment but are usually developed from...Background CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed.Machine learning techniques can provide rapid automated CT assessment but are usually developed from annotated images which necessarily limits the size and representation of development data sets.We aimed to develop a deep learning(DL)method using CT brain scans that were labelled but not annotated for the presence of ischaemic lesions.Methods We designed a convolutional neural network-based DL algorithm to detect ischaemic lesions on CT.Our algorithm was trained using routinely acquired CT brain scans collected for a large multicentre international trial.These scans had previously been labelled by experts for acute and chronic appearances.We explored the impact of ischaemic lesion features,background brain appearances and timing of CT(baseline or 24–48 hour follow-up)on DL performance.Results From 5772 CT scans of 2347 patients(median age 82),54%had visible ischaemic lesions according to experts.Our DL method achieved 72%accuracy in detecting ischaemic lesions.Detection was better for larger(80%accuracy)or multiple(87%accuracy for two,100%for three or more)lesions and with follow-up scans(76%accuracy vs 67%at baseline).Chronic brain conditions reduced accuracy,particularly non-stroke lesions and old stroke lesions(32%and 31%error rates,respectively).Conclusion DL methods can be designed for ischaemic lesion detection on CT using the vast quantities of routinely collected brain scans without the need for lesion annotation.Ultimately,this should lead to more robust and widely applicable methods.展开更多
Background Prehospital delay in acute ischaemic stroke(AIS)remains prevalent in China.We aimed to assess the status of the onset-to door time(ODT)in AIS and analyse its influencing factors.Methods Data were collected ...Background Prehospital delay in acute ischaemic stroke(AIS)remains prevalent in China.We aimed to assess the status of the onset-to door time(ODT)in AIS and analyse its influencing factors.Methods Data were collected from a prospective multicentre hospital-based registry(China National Cerebrovascular Disease Prevention and Control Project Management Special Database)of patients with AIS involving 21 hospitals across different economic and geographical regions in China in 2022.The Mann-Whitney U test or t-test was used for between-group comparisons.Factors influencing ODT≤3 hours were analysed using a binary logistic regression model.Results Of the included 12484 patients(attended middle school or below,69.2%),females had a higher illiteracy rate(13.1%)than males(4.8%);94.8%were living with others at illness onset;22.5%of patients/family members were aware of the stroke emergency map(SEM,but only 7.3%were transported by SEM;76.8%lived within 20 km of the first visited hospital.Significant differences occurred in modes of arrival at hospitals among cities of different sizes(χ²=74.882,p<0.001).Being in a medium-sized(OR 0.65,95%CI 0.50 to 0.86);large(OR 0.61,95%CI 0.47 to 0.79)or extralarge city(OR 0.60,95%CI 0.46 to 0.78);experiencing cardiogenic embolism(OR 0.65,95%CI 0.50 to 0.86)or stroke of undetermined aetiology(OR 0.69,95%CI 0.52 to 0.92);stroke onset between 18:00 and 23:59(OR 0.71,95%CI 0.60 to 0.85);distance<20 km from onset location to the hospital(OR 0.47,95%CI 0.41 to 0.54);being transported by SEM(OR 0.31,95%CI 0.26 to 0.36)and having initial National Institutes of Health Stroke Scale scores of 5-15(OR 0.63,95%CI 0.57 to 0.71)or 16-42(OR 0.32,95%CI 0.27 to 0.39)were independent factors favouring ODT≤3 hours.Conversely,being transferred between hospitals during transportation(OR 3.31,95%CI 2.66 to 4.14);experiencing wake-up stroke(OR 2.00,95%CI 1.67 to 2.38);symptom-onset including dizziness(OR 1.28,95%CI 1.10 to 1.47)and prestroke modified Rankin scale(mRS)score of 2-3(OR 1.58,95%CI 1.30 to 1.92)or 4-5(OR 1.48,95%CI 1.02 to 2.15)tended to indicate ODT>3 hours.Conclusions Urban scale,stroke type,onset time,distance from initial location to the first hospital visit,transportation method,stroke symptoms,prestroke mRS score and stroke severity significantly influenced prehospital delay.Our findings can facilitate the development of targeted policies.展开更多
Background Inflammation and blood-brain barrier disruption may contribute to the pathogenesis of ischaemic stroke.Minocycline was shown to exert anti-inflammatory effects by attenuating microglial activation and prote...Background Inflammation and blood-brain barrier disruption may contribute to the pathogenesis of ischaemic stroke.Minocycline was shown to exert anti-inflammatory effects by attenuating microglial activation and protecting blood-brain barrier in preclinical studies.Previous small-scale clinical studies have suggested that minocycline may have a potential beneficial effect on prognosis in acute ischaemic stroke.However,the efficacy and safety of minocycline in patients with acute ischaemic stroke need to be further confirmed.Study aims We designed the study,Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke(EMPHASIS),to evaluate the effect of minocycline in improving the functional outcome and the drug safety in patients with acute ischaemic stroke.Methods The EMPHASIS study is a multicentre,randomised,double-blind,placebo-controlled trial aiming to recruit patients with acute ischaemic stroke.Patients who had ischaemic stroke within 72 hours of onset,a National Institutes of Health Stroke Scale score between 4 and 25 and Ia≤1(moderate-to severe)will be randomly allocated to either minocycline or placebo groups in a 1:1 ratio.Patients will receive minocycline(or placebo)with a loading dose of 200 mg,and subsequent 100 mg every 12 hours for 4 days.All patients will receive routine guideline-based treatment.The primary efficacy outcome is an excellent functional outcome assessed by the proportion of modified Rankin Scale score of 0-1 at 90±7 days.The main safety outcomes include the number of symptomatic intracranial haemorrhage at 24±2 hours and 6±1 days.Discussion The EMPHASIS trial is the first phase III trial to investigate whether minocycline is effective and safe in improving functional outcome at 90 days in patients with moderate-to severe acute ischaemic stroke.The data generated may provide valuable evidence of a potential anti-inflammation treatment for ischaemic stroke.展开更多
Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its...Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.展开更多
Background Research data regarding the correlation between elevated oxidised low-density lipoprotein(oxLDL)cholesterol concentrations and unfavourable clinical outcomes in individuals experiencing minor acute ischaemi...Background Research data regarding the correlation between elevated oxidised low-density lipoprotein(oxLDL)cholesterol concentrations and unfavourable clinical outcomes in individuals experiencing minor acute ischaemic cerebrovascular events or transient ischaemic attack(TIA)with presumed atherosclerotic aetiology are still limited.Methods This investigation incorporated a cohort of 5814 participants derived from the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis clinical trial.The core laboratory conducted blinded measurements of baseline plasma oxLDL concentrations.Multivariable Cox regression analyses were employed to assess the correlations between oxLDL levels and adverse clinical events.The principal endpoint for efficacy assessment was defined as the occurrence of stroke within a 90-day follow-up period.Additional secondary endpoints encompassed composite vascular events during the same observation window.The main safety endpoint assessed was the occurrence of bleeding events of moderate to severe intensity.Results The final analytical cohort comprised 5814 patients included in the final analysis.The mean age was 63.7±9.6 years,and 36.0%were female.The average concentration of circulating oxLDL was 36.62μg/dL.Elevated oxLDL concentrations demonstrated a potential correlation with heightened stroke risk(T3 vs T1:HR 1.39,95%CI 1.04 to 1.85),ischaemic stroke(T3 vs T1:HR 1.31,95%CI 0.98 to 1.76)and composite vascular events(T3 vs T1:HR 1.36,95%CI 1.02 to 1.81)within 90 days.An increased concentration of oxLDL demonstrated a significant association with elevated susceptibility to moderate and severe haemorrhagic events(T3 vs T1:HR 3.61,95%CI 1.26 to 10.34)within 90 days.Conclusion Increased concentrations of oxLDL demonstrated an independent correlation with both stroke recurrence and the occurrence of moderate-to severe haemorrhagic events in individuals presenting with acute minor ischaemic stroke or TIA at elevated risk,accompanied by intracranial or extracranial atherosclerotic lesions.展开更多
Background Advances in endovascular thrombectomy(EVT)and extended treatment criteria have improved outcomes in acute ischaemic stroke(AIS).However,contrast staining(CS)on postoperative CT complicates clinical decision...Background Advances in endovascular thrombectomy(EVT)and extended treatment criteria have improved outcomes in acute ischaemic stroke(AIS).However,contrast staining(CS)on postoperative CT complicates clinical decision-making and outcome evaluation.We investigated the association between postoperative CS and 90-day clinical outcomes in AIS patients.Methods In this multicentre observational study,we enrolled AIS patients treated with EVT who underwent non-contrast CT(NCCT)within 2 hours postprocedure.Patients were stratified into two groups based on the presence or absence of CS to further explore the relationship between CS characteristics and clinical outcomes.The primary outcome was poor functional outcome,defined as a modified Rankin Scale score≥3 at 90 days,evaluated with the logistic regression analysis adjusted for age,sex and other clinical features.Results Among the 420 patients(mean age 63 years;74.3%male),CS was observed in 250(59.5%)following EVT.Logistic regression analysis showed that CS was strongly associated with poor functional outcomes.At 3 months,the proportion of patients with functional dependence was significantly higher in the CS group(76.8%)compared with the non-CS group(62.4%).In addition,the CS group exhibited a higher death rate compared with the non-CS group(p=0.028).Our study found that CS in the pons,as well as larger and denser staining volumes,was often indicative of poor prognosis.Conclusion In around half of AIS patients with EVT,CS can be observed and independently associate with poor clinical outcomes,primarily related to the location and density of CS.展开更多
Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined ...Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.展开更多
Background Mechanical thrombectomy(MT)improves outcomes in patients who had an acute ischaemic stroke due to large vessel occlusion(LVO).However,socioeconomic status(SES)can influence recovery and prognosis.This study...Background Mechanical thrombectomy(MT)improves outcomes in patients who had an acute ischaemic stroke due to large vessel occlusion(LVO).However,socioeconomic status(SES)can influence recovery and prognosis.This study investigated the effect of SES,assessed via the Index of Multiple Deprivation(IMD),on MT outcomes in a multicentre London cohort.Methods This retrospective study included patients with anterior circulation LVO treated with MT between 2021 and 2023 at three London hospitals.Patients were grouped into IMD1-5(more deprived)and IMD6-10(less deprived).Inverse probability weighting balanced baseline characteristics.Primary outcomes were 90-day functional independence(modified Rankin Scale(mRS)0-2)and 90-day mRS shift.Secondary outcomes included recanalisation,early neurological changes,90-day mortality,symptomatic intracerebral haemorrhage(sICH)and haemorrhagic transformation(HT).Subgroup analyses explored interactions between IMD and demographic or clinical factors.LASSO(Least Absolute Shrinkage and Selection Operator)regression identified predictors of functional independence,while receiver operating characteristic analysis evaluated IMD’s predictive value.Results Among 1219 patients with acute LVO ischemic stroke treated with MT,533(43.7%)were in IMD1-5 and 686(56.3%)in IMD6-10.IMD1-5 patients had lower odds of functional independence at 90 days(RR 0.79,95%CI 0.70 to 0.90)and worse mRS shift(OR 1.29,95%CI 1.06 to 1.58).They also had higher risks of sICH(RR 2.07,95%CI 1.54 to 2.67)and HT(Risk Ratio 1.47,95%CI 1.21 to 1.80).Subgroup analysis highlighted IMD’s predictive importance in Asian or mixed ethnicity groups.A model incorporating IMD,age,sex,hypertension and National Institutes of Health Stroke Scale(area under the curve 0.656)demonstrated predictive accuracy for 90-day functional independence.Conclusions Lower SES correlates with worse outcomes and higher complications post-MT,even within a universal healthcare system.Addressing SES disparities could improve stroke care equity.展开更多
Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with altepl...Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.展开更多
Background Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis(IVT)for mild acute ischaemic stroke(AIS),with National Institutes of Health S...Background Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis(IVT)for mild acute ischaemic stroke(AIS),with National Institutes of Health Stroke Scale score 0-5.Objective To compare the benefits and risks of antiplatelet therapy and IVT in patients with mild AIS.Methods A systematic search of MEDLINE,Embase and Cochrane Library was conducted from database inception until July 2023,without language restriction.Randomised clinical trials(RCTs)or observational studies were selected.The primary outcomes were 90-day functional outcomes,measured by the modified Rankin Scale(mRS)score.The protocol has been registered before data collection.Results Two RCTs and four observational studies with relatively low risk of bias that enrolled 3975 patients were analysed(2454 in antiplatelet therapy and 1521 in IVT therapy).There were no significant differences between antiplatelet therapy and IVT in 90-day functional outcomes(mRS 0-1,OR 1.08(95%CI 0.73 to 1.58);mRS 0-2,OR,1.04(95%CI 0.63 to 1.73)),death(OR,0.64(95%CI 0.19 to 2.13))and stroke recurrence(OR,0.71(95%CI 0.28 to 1.79)).Antiplatelet therapy was associated with a reduced risk of symptomatic intracranial haemorrhage(sICH)compared with IVT(OR,0.20(95%CI 0.06 to 0.69)).Conclusions Among patients with mild AIS,compared with IVT,early application of antiplatelet therapy was not significantly associated with improved functional outcomes,reduced death or stroke recurrence,but was significantly associated with a reduced risk of sICH.展开更多
Background Statins are essential for secondary prevention after ischaemic stroke(IS).However,statin intensity recommendations differ,and there is a concern about intracerebral haemorrhage(ICH).We studied the long-term...Background Statins are essential for secondary prevention after ischaemic stroke(IS).However,statin intensity recommendations differ,and there is a concern about intracerebral haemorrhage(ICH).We studied the long-term impacts of initial statin intensity following IS.Methods Consecutive patients using high-intensity,moderate-intensity or low-intensity statin early after IS(n=45512)were retrospectively studied using national registries in Finland.Differences were adjusted using multivariable regression.The primary outcome was all-cause death within 12-year follow-up(median 5.9 years).Secondary outcomes were recurrent IS,cardiovascular death and ICH studied using competing risk analyses.Results High-intensity therapy was initially used by 16.0%,moderate-intensity by 73.8%and low-intensity by 10.2%.Risk of death was lower with high-intensity versus moderate-intensity(adjusted HR(adj.HR)0.92;95%CI 0.87 to 0.97;number needed to treat(NNT)32.0),with moderate-intensity versus low-intensity(adj.HR 0.91;95%CI 0.87 to 0.95;NNT 27.5)and with high-intensity versus low-intensity(adj.HR 0.83;95%CI 0.78 to 0.89;NNT 14.6)statin.There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS(p<0.0001)and cardiovascular death(p<0.0001).The occurrence of ICH was not associated with initial statin intensity(p=0.646).Conclusions Following IS,more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH.These findings emphasise the importance of high statin intensity shortly after IS.展开更多
Background Stroke is a major cause of global mortality and disability.Currently,the treatment of acute ischaemic stroke through reperfusion has posed several challenges,raising the need for complementary options to pr...Background Stroke is a major cause of global mortality and disability.Currently,the treatment of acute ischaemic stroke through reperfusion has posed several challenges,raising the need for complementary options to protect the ischaemic penumbra.Recent investigations have indicated that certain epigenetic factors,specifically,histone deacetylases(HDACs)and sirtuins,can be promising for ischaemic stroke therapy,with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke.However,the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain.This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.Methods This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke.The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Electronic searches will be conducted in PubMed,Web of Science and Scopus,with subsequent screening by independent reviewers based on the established eligibility criteria.Methodological quality will be evaluated using the SYRCLE risk of bias tool.The primary outcomes will be infarct volume and functional response,with the secondary outcomes established a priori.Data pertaining to infarct volume will be used for random-effects meta-analysis.Additionally,a descriptive summary will be conducted for the functional response and secondary outcomes.Discussion No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date.A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.展开更多
Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy o...Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke(AIS).Methods A double-blind,randomised,placebo-controlled,phase 2 trial was conducted at 15 clinical sites in China.Patients aged 18-80 years with AIS within 48 hours were randomly assigned(1:1:1)to receive 160 mg GD-11,80 mg GD-11 and placebo,two times a day for 10 days.The primary endpoint was a modified Rankin Scale(mRS)score of 0-1 at 90 days after treatment.The safety outcome was any adverse events within 90 days.Results From 17 November 2022 to 22 March 2023,a total of 80 patients in the 160 mg GD-11 group,79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included.The proportion of an mRS score of 0-1 at day 90 was 77.5%in the 160 mg GD-11 group,72.2%in the 80 mg GD-11 group and 67.5%in the placebo group.Though no significant difference was found(p=0.3671),a numerically higher proportion was observed in the GD-11 group,especially in the 160 mg GD-11 group.The incidence of adverse events was similar across the three groups(p=0.1992).Conclusion GD-11 was safe and well-tolerated.A dosage of GD-11160 mg two times a day was recommended for a large trial to investigate the efficacy.展开更多
基金funded by Tianjin Municipal Health Commission(TJWJ2023QN115)。
文摘Background Cognitive decline is a significant concern for stroke survivors,affecting their quality of life and increasing their burden on the healthcare system.DL-3-n butylphthalide(butylphthalide)has shown efficacy in the short-term treatment of various cognitive impairments.This study evaluated the efficacy of butylphthalide in preventing cognitive decline over a 12-month period in patients with ischaemic stroke.Methods This prospective following-up study involved patients newly diagnosed with ischaemic stroke between 1 month and 6 months after stroke onset and not in the acute phase.Patients were assigned to either the butylphthalide or control group.Cognitive function was assessed using the mini-mental state examination(MMSE)at baseline and at the 12-month follow-up.Statistical analyses included t-tests,χ2 tests and multivariate regression analyses.Results Butylphthalide was negatively associated with the MMSE D-value(β=−0.122;95%CI−1.932 to−0.298;p=0.003)and the MMSE D-value percentage(β=−0.117;95%CI−0.057 to−0.011;p=0.004).A multivariate analysis indicated that butylphthalide treatment was negatively associated with both changes in orientation and language score.Additionally,the incidence of cognitive decline was significantly lower in the butylphthalide group(OR,0.612;p=0.020)than the control group.An age of≥60 years and lower educational level were identified as risk factors for lower cognitive score and cognitive decline.Conclusion This study demonstrated that butylphthalide is effective in preventing cognitive decline in patients with ischaemic stroke.These findings have significant implications for clinical practice,suggesting that butylphthalide could be incorporated into standard post-stroke care regimens to improve patient outcomes and reduce the healthcare burden.Additional multicentre double-blind trials are recommended to confirm these results in diverse populations.
基金Beijing Physician Scientist Training Project(BJPSTP-2024-04)National Natural Science Foundation of China(8207146882271507)Beijing Science Foundation for Distinguished Young Scholars(JQ24041)。
文摘Rationale Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke(AIS).Preclinical research indicates that tocilizumab,an interleukin-6 receptor antagonist,can attenuate ischaemia-reperfusion damage by exerting anti-inflammatory and neuroprotective effects.Aim To determine tocilizumab’s efficacy and safety when combined with endovascular thrombectomy(EVT)in patients with acute anterior circulation large vessel occlusion(LVO).Sample size estimates To determine a 30%decrease in average infarct core volume comparing the intervention and historical control groups(mean increase of 18.7 mL(SD=9.7 mL)post-thrombectomy)via a two-sided test(alpha=0.05,power=80%),accounting for a 10%drop-out rate,we plan to recruit 108 participants.Methods and design This trial is designed as a randomised,multicentre,double-blind,placebo-controlled trial.Patients will be randomly and evenly allocated to the tocilizumab or placebo groups.Study outcomes The primary endpoint is the change in infarct core volume between baseline and 72 hours post-treatment.Secondary outcomes include the 90-day modified Rankin scale score(0–2,indicating functional independence).The key safety endpoints include 90-day mortality and symptomatic intracerebral haemorrhage within 72 hours after EVT.Discussion Administering tocilizumab within 24 hours of stroke as an adjunct to EVT may effectively reduce the infarct core volume for patients experiencing AIS with anterior circulation LVO,potentially improving functional outcomes in these patients.
基金This work was supported by a grant to Dr.Ulvi Bayraktutan from the Dunhill Medical Trust(R459/0216)The funder had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.The contents are solely the responsibility of the author and do not necessarily represent the official views of the DMT.
文摘Ischaemic stroke is a debilitating disease with immense personal,societal and economic impact.Thrombolysis with recombinant tissue plasminogen activator remains the only approved pharmacotherapy for this disease.As each year less than 1%of eligible patients receive this therapy worldwide,efficacious new therapeutics are desperately needed.Emerging evidence suggest endothelial progenitor cells(EPCs),capable of repairing damaged vasculature,as one such therapeutics.However,questions regarding their optimal dose,delivery route and in vivo survivability remain largely unanswered.Outgrowth endothelial cells,generated in large numbers by ex vivo expansion of EPCs,enable effective assessment of these issues and may eventually serve as off-the-shelf therapeutics.Correlations between circulating EPC levels and stroke outcome imply that EPCs may also serve as clinical biomarkers for stroke.This viewpoint briefly evaluates the current evidence,pinpoints the gaps in the literature and proposes new directions for research.
文摘Ischaemic stroke is one of the commonest causes of morbidity and mortality worldwide and around a fifth of events can be attributed to a cardioembolic source. This is typically due to atrial fibrillation(AF), the most common sustained cardiac arrhythmia. However, AF can, at times, be difficult to detect due to a relative lack of symptoms and the fact that it can be paroxysmal in nature. Studies have shown that diagnosis of AF improves as the length of cardiac monitoring increases. However, prolonged cardiac monitoring is not a costeffective way of diagnosing AF. Therefore, an alternative approach may be to empirically anticoagulate individuals who are at high risk of stroke. This article summarises current evidence surrounding stroke risk prediction, the use of anticoagulation in the secondary prevention of stroke and its use in the primary prevention of stroke in high risk groups with the aim of determining whether empirical anticoagulation is a safe and effective strategy.
基金This study was supported by Hainan Provincial Key Research and Development Plan(ZDYF2021SHFZ092,ZDYF2022SHFZ109),Hainan Provincial Natural Science Foundation(822RC832)Hainan Provincial Clinical Medical Center(2021)Epilepsy Research Innovation Team of Hainan Medical College(2022)。
文摘Objective:To screen risk factors for epilepsy after acute ischaemic stroke based on meta-analysis and cohort study and to establish a predictive model.Methods:Computer searches of MEDLINE,Embase,Cochrane library,Web of Scinence,PubMed,CNKI,and WanFang Data data were conducted to collect literature on epilepsy after in acute ischemic stroke,from database creation to September 1,2022.The RRs and their 95%confidence intervals(CI)for risk factors for post stroke epilepsy were extracted for each study,and pooled estimates of the RRs and 95%CIs for each study were generated using either a random-effects model or a fixed-effects model.Beta coefficients for each risk factor were calculated based on the combined RR and their corresponding 95%CIs.The beta coefficients were multiplied by 10 and rounded.Results:Ten articles were identified for final inclusion in this meta-analysis,with a total of 141948 cases and 3702 cases of post stroke epilepsy.The risk factors included in the final risk prediction model were infarct size(RR 4.67,95%CI 1.41~15.47;P=0.01),stroke recuRRence(RR 2.48,95%CI 2.01~3.05;P<0.00001),stroke etiology(RR 1.70,95%CI 1.34~2.15;P<0.00001),stroke severity(RR 1.70,95%CI 1.34~2.15;P<0.00001),and stroke risk.stroke severity(RR 1.53,95%CI 1.39~1.70;P<0.00001),NIHSS score(RR 2.91,95%CI 1.64~5.61;P=0.0003),early-onset epilepsy(RR 5.62,95%CI 5.08~6.22;P<0.00001),cortical lesions(RR 3.83.95%CI 2.23~6.58;P<0.00001),total anterior circulation infarction(RR 18.94,95%CI 10.38~34.57;P<0.00001),partial anterior circulation infarction(RR 4.39,95%CI 2.29~8.40;P<0.00001),cardiovascular events(RR 1.78,95%CI 1.59~1.99;P<0.00001).Conclusion:Based on a systematic review and meta-analysis,we developed a simple risk prediction model for late epilepsy in baseline ischemic stroke that integrates clinical risk factors,including infarct size,stroke recurrence,stroke etiology,stroke severity,NIHSS score,early onset epilepsy,cortical lesions,stroke subtype,and cardiovascular events.
文摘<strong>Introduction:</strong> Ischemic strokes represent a classic complication of infective endocarditis (IE) and are most often related to the fragmentation of valvular vegetation. In most cases, they occur in the Sylvian territory and are related to<em> Staphylococcus aureus</em>. MRI can demonstrate, in addition to the AVCI image, cerebral microbleeds (CMBs) that are very suggestive of the diagnosis. We present the case of a patient who presented an ischemic stroke occurring in the context of infective endocarditis.<strong> Observation:</strong> A 32-year-old woman with no previous medical history initially presented with acute febrile headache, two weeks later she developed right hemiplegia with aphasia in the context of fever. Her general examination revealed lesions on the soles of her feet, in the form of nodules, infected in places, suggestive of Janeway nodules (characteristic of IE). The brain MRI showed an ischemic stroke in the Sylvian territory, with the presence of multiple microbleeds on the magnetic susceptibility sequences. The biological examination showed a severe inflammatory syndrome;the transthoracic echocardiography (TTE) confirmed the presence of vegetation on the aortic valve;and the blood cultures showed a <em>Staphylococcus aureus</em>. Antibiotic therapy was started, and the patient was transferred to the cardiology department. <strong>Discussion: </strong>Our observation has a double interest. The first is clinical due to the presence of plantar nodules (Janeway’s nodules) that are characteristic of IE which should orientate the diagnosis before the installation of the stroke, and the second is radiological and linked to the discovery of microbleeds. Their presence is increasingly reported in the literature, but their pathophysiology is not yet very clear. <strong>Conclusion:</strong> Stroke is the most frequent extracardiac complication during IE. The presence of microbleeds contributes to early diagnosis, especially in asymptomatic forms.
基金funded by a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(Grant no-NA)Project of MOE Key Laboratory of Geriatric Diseases and Immunology(JYN202406)+1 种基金Interdisciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow University(YXY2302013)National Natural Science Foundation of China(82273706 and 82220108001).
文摘Background Whether mean arterial pressure(MAP)and pulse pressure(PP),two indicators of cerebral perfusion,could guide the selection of anti-hypertensive strategies after acute ischaemic stroke remains uncertain.Our study was to explore the impact of early anti-hypertensive intervention on adverse clinical outcomes following ischaemic stroke stratified by the levels of MAP and PP based on the China Antihypertensive Trial in Acute Ischemic Stroke(CATIS).Methods The trial randomised 4071 acute ischaemic stroke patients with elevated systolic blood pressure(SBP)to receive anti-hypertensive treatment(targeting a 10%-25%reduction in SBP during the 24 hours postrandomisation,reaching a BP level<140/90 mm Hg in 7 days,further keeping these levels throughout hospitalisation)or discontinue anti-hypertensive treatment during hospitalisation.The primary outcome was death or major disability at 14 days or hospital discharge.Study outcomes were analysed by comparing the BP-lowering intervention group and control group,stratified by tertiles of MAP or PP levels.Results No significant difference was observed in the primary outcome between the intervention and control groups across all MAP(p=0.69 for homogeneity)and PP(p=0.78 for homogeneity)categories.The corresponding odds ratios(95%CIs)were 1.08(0.85-1.36),0.92(0.74-1.15)and 1.00(0.81-1.25)for participants with low,intermediate,and high MAP and were 0.99(0.79-1.25),1.06(0.84-1.34)and 0.95(0.77-1.18)for participants in PP subgroups,respectively.Furthermore,early anti-hypertensive intervention was not associated with secondary outcomes(including neurological deterioration,recurrent stroke,vascular events and all-cause mortality)by MAP and PP(all p>0.05).Conclusions Early anti-hypertensive therapy neither decreased nor increased the odds of major disability,mortality,recurrent stroke or vascular events in patients with acute ischaemic stroke regardless of different MAP and PP levels.
基金Health Data Research UK(Grant ID:EDIN1)The Royal College of Radiologists’2018 Pump Priming Grant and the UK Dementia Research Institute+2 种基金IST-3 was funded chiefly by the UK Medical Research Council(MRC G0400069,EME 09-800-15)the UK Stroke Association.GM is a Stroke Association Edith Murphy Foundation Senior Clinical Lecturer(SA L-SMP 18\1000)UK Research and Innovation(grant EP/S02431X/1)UKRI Centre for Doctoral Training in Biomedical AI at the University of Edinburgh,School of Informatics.
文摘Background CT is commonly used to image patients with ischaemic stroke but radiologist interpretation may be delayed.Machine learning techniques can provide rapid automated CT assessment but are usually developed from annotated images which necessarily limits the size and representation of development data sets.We aimed to develop a deep learning(DL)method using CT brain scans that were labelled but not annotated for the presence of ischaemic lesions.Methods We designed a convolutional neural network-based DL algorithm to detect ischaemic lesions on CT.Our algorithm was trained using routinely acquired CT brain scans collected for a large multicentre international trial.These scans had previously been labelled by experts for acute and chronic appearances.We explored the impact of ischaemic lesion features,background brain appearances and timing of CT(baseline or 24–48 hour follow-up)on DL performance.Results From 5772 CT scans of 2347 patients(median age 82),54%had visible ischaemic lesions according to experts.Our DL method achieved 72%accuracy in detecting ischaemic lesions.Detection was better for larger(80%accuracy)or multiple(87%accuracy for two,100%for three or more)lesions and with follow-up scans(76%accuracy vs 67%at baseline).Chronic brain conditions reduced accuracy,particularly non-stroke lesions and old stroke lesions(32%and 31%error rates,respectively).Conclusion DL methods can be designed for ischaemic lesion detection on CT using the vast quantities of routinely collected brain scans without the need for lesion annotation.Ultimately,this should lead to more robust and widely applicable methods.
基金funded by Shenzhen Second People’s Hospital Clinical Research Fund of Shenzhen High-level Hospital Construction Projects(20243357001)the Shenzhen Program for Integration Prevention and Cure of Nervous System Disease(None),the Research and Promotion Project on Appropriate Intervention Techniques for High-Risk Stroke Population(GN-2020R0002)+1 种基金Shenzhen Clinical Research Center for Neurological Diseases(LCYSSQ 20220823091204009)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0504800,2023ZD0504802).
文摘Background Prehospital delay in acute ischaemic stroke(AIS)remains prevalent in China.We aimed to assess the status of the onset-to door time(ODT)in AIS and analyse its influencing factors.Methods Data were collected from a prospective multicentre hospital-based registry(China National Cerebrovascular Disease Prevention and Control Project Management Special Database)of patients with AIS involving 21 hospitals across different economic and geographical regions in China in 2022.The Mann-Whitney U test or t-test was used for between-group comparisons.Factors influencing ODT≤3 hours were analysed using a binary logistic regression model.Results Of the included 12484 patients(attended middle school or below,69.2%),females had a higher illiteracy rate(13.1%)than males(4.8%);94.8%were living with others at illness onset;22.5%of patients/family members were aware of the stroke emergency map(SEM,but only 7.3%were transported by SEM;76.8%lived within 20 km of the first visited hospital.Significant differences occurred in modes of arrival at hospitals among cities of different sizes(χ²=74.882,p<0.001).Being in a medium-sized(OR 0.65,95%CI 0.50 to 0.86);large(OR 0.61,95%CI 0.47 to 0.79)or extralarge city(OR 0.60,95%CI 0.46 to 0.78);experiencing cardiogenic embolism(OR 0.65,95%CI 0.50 to 0.86)or stroke of undetermined aetiology(OR 0.69,95%CI 0.52 to 0.92);stroke onset between 18:00 and 23:59(OR 0.71,95%CI 0.60 to 0.85);distance<20 km from onset location to the hospital(OR 0.47,95%CI 0.41 to 0.54);being transported by SEM(OR 0.31,95%CI 0.26 to 0.36)and having initial National Institutes of Health Stroke Scale scores of 5-15(OR 0.63,95%CI 0.57 to 0.71)or 16-42(OR 0.32,95%CI 0.27 to 0.39)were independent factors favouring ODT≤3 hours.Conversely,being transferred between hospitals during transportation(OR 3.31,95%CI 2.66 to 4.14);experiencing wake-up stroke(OR 2.00,95%CI 1.67 to 2.38);symptom-onset including dizziness(OR 1.28,95%CI 1.10 to 1.47)and prestroke modified Rankin scale(mRS)score of 2-3(OR 1.58,95%CI 1.30 to 1.92)or 4-5(OR 1.48,95%CI 1.02 to 2.15)tended to indicate ODT>3 hours.Conclusions Urban scale,stroke type,onset time,distance from initial location to the first hospital visit,transportation method,stroke symptoms,prestroke mRS score and stroke severity significantly influenced prehospital delay.Our findings can facilitate the development of targeted policies.
基金National Natural Science Foundation of China(No.81825007,82271516)Beijing Healthunion Cardio-cerebrovascular Disease Prevention and Treatment Foundation(No.20230418-J E 010).
文摘Background Inflammation and blood-brain barrier disruption may contribute to the pathogenesis of ischaemic stroke.Minocycline was shown to exert anti-inflammatory effects by attenuating microglial activation and protecting blood-brain barrier in preclinical studies.Previous small-scale clinical studies have suggested that minocycline may have a potential beneficial effect on prognosis in acute ischaemic stroke.However,the efficacy and safety of minocycline in patients with acute ischaemic stroke need to be further confirmed.Study aims We designed the study,Efficacy and Safety of Minocycline in Patients with Moderate to Severe Acute Ischaemic Stroke(EMPHASIS),to evaluate the effect of minocycline in improving the functional outcome and the drug safety in patients with acute ischaemic stroke.Methods The EMPHASIS study is a multicentre,randomised,double-blind,placebo-controlled trial aiming to recruit patients with acute ischaemic stroke.Patients who had ischaemic stroke within 72 hours of onset,a National Institutes of Health Stroke Scale score between 4 and 25 and Ia≤1(moderate-to severe)will be randomly allocated to either minocycline or placebo groups in a 1:1 ratio.Patients will receive minocycline(or placebo)with a loading dose of 200 mg,and subsequent 100 mg every 12 hours for 4 days.All patients will receive routine guideline-based treatment.The primary efficacy outcome is an excellent functional outcome assessed by the proportion of modified Rankin Scale score of 0-1 at 90±7 days.The main safety outcomes include the number of symptomatic intracranial haemorrhage at 24±2 hours and 6±1 days.Discussion The EMPHASIS trial is the first phase III trial to investigate whether minocycline is effective and safe in improving functional outcome at 90 days in patients with moderate-to severe acute ischaemic stroke.The data generated may provide valuable evidence of a potential anti-inflammation treatment for ischaemic stroke.
基金National Natural Science Foundation of China(82271352)the Science and Technology Commission of Shanghai Municipality(20Z11900802)the Shanghai Municipal Health Commission(2022XD022).
文摘Background and aims Tenecteplase(TNK)offers logistical advantages in stroke thrombolytic therapy with its single bolus administration compared with alteplase.We aim to investigate the real-world evidence regarding its safety and effectiveness in China.Methods We conducted a retrospective study on patients receiving alteplase or TNK for acute ischaemic stroke(AIS)within 4.5 hours of onset between 1 March 2019 and 1 October 2023,from 18 stroke centres in China.Using propensity score matching(PSM),TNK-treated patients were matched 1:1 with alteplase-treated patients.The primary outcome was the rate of symptomatic intracranial haemorrhage(sICH)within 72 hours post-thrombolysis.Secondary outcomes comprised the rate of parenchymal haemorrhage type 2,any intracranial haemorrhage,any systematic bleeding and mortality at 90 days,as well as 24-hour National Institutes of Health Stroke Scale(NIHSS),early neurological improvement at 24 hours,modified Rankin Scale(mRS)shift,percentage of mRS 0-1 and mRS 0-2 at 90 days.Results We identified 1113 patients with AIS who received TNK and 2360 patients who received alteplase.Following PSM,1113 TNK-treated patients with AIS were matched to 1113 patients treated with alteplase.No significant differences were observed in rates of sICH(1.8%vs 1.98%,p=0.864)or other safety outcomes.Moreover,TNK-treated patients demonstrated a lower rate of any intracranial haemorrhage(OR:0.51,95%CI:0.31 to 0.86,p=0.012).A higher proportion of patients achieving early neurological improvement at 24 hours(OR:1.76,95%CI:1.48 to 2.09,p=0.000),better 90-day mRS(OR:0.67,95%CI:0.57 to 0.79,p=0.000)as well as higher percentages of 90-day mRS 0-1(OR:1.27,95%CI:1.05 to 1.54,p=0.012)and mRS 0-2(OR:1.41,95%CI:1.14 to 1.75,p=0.001)compared with alteplase.Conclusions Thrombolysis with TNK is not associated with an increased risk of sICH,and may result in better early neurological improvement and 90-day functional outcomes compared with alteplase in patients with AIS.
基金supported by the Capital’s Funds for Health Improvement and Research(2024-1-2043)National Natural Science Foundation of China(No.82425101,No.82101358)+3 种基金Beijing Nova Program(20230484336)Capital's Funds for Health Improvement and Research(2022-2-2045)the National Key R&D Program of China(No.2022YFF1501500,2022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,2022YFF1501505,2017YFC1307900,2017YFC1307905)Beijing Laboratory of Oral Health(PXM2021_014226_000041).
文摘Background Research data regarding the correlation between elevated oxidised low-density lipoprotein(oxLDL)cholesterol concentrations and unfavourable clinical outcomes in individuals experiencing minor acute ischaemic cerebrovascular events or transient ischaemic attack(TIA)with presumed atherosclerotic aetiology are still limited.Methods This investigation incorporated a cohort of 5814 participants derived from the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis clinical trial.The core laboratory conducted blinded measurements of baseline plasma oxLDL concentrations.Multivariable Cox regression analyses were employed to assess the correlations between oxLDL levels and adverse clinical events.The principal endpoint for efficacy assessment was defined as the occurrence of stroke within a 90-day follow-up period.Additional secondary endpoints encompassed composite vascular events during the same observation window.The main safety endpoint assessed was the occurrence of bleeding events of moderate to severe intensity.Results The final analytical cohort comprised 5814 patients included in the final analysis.The mean age was 63.7±9.6 years,and 36.0%were female.The average concentration of circulating oxLDL was 36.62μg/dL.Elevated oxLDL concentrations demonstrated a potential correlation with heightened stroke risk(T3 vs T1:HR 1.39,95%CI 1.04 to 1.85),ischaemic stroke(T3 vs T1:HR 1.31,95%CI 0.98 to 1.76)and composite vascular events(T3 vs T1:HR 1.36,95%CI 1.02 to 1.81)within 90 days.An increased concentration of oxLDL demonstrated a significant association with elevated susceptibility to moderate and severe haemorrhagic events(T3 vs T1:HR 3.61,95%CI 1.26 to 10.34)within 90 days.Conclusion Increased concentrations of oxLDL demonstrated an independent correlation with both stroke recurrence and the occurrence of moderate-to severe haemorrhagic events in individuals presenting with acute minor ischaemic stroke or TIA at elevated risk,accompanied by intracranial or extracranial atherosclerotic lesions.
文摘Background Advances in endovascular thrombectomy(EVT)and extended treatment criteria have improved outcomes in acute ischaemic stroke(AIS).However,contrast staining(CS)on postoperative CT complicates clinical decision-making and outcome evaluation.We investigated the association between postoperative CS and 90-day clinical outcomes in AIS patients.Methods In this multicentre observational study,we enrolled AIS patients treated with EVT who underwent non-contrast CT(NCCT)within 2 hours postprocedure.Patients were stratified into two groups based on the presence or absence of CS to further explore the relationship between CS characteristics and clinical outcomes.The primary outcome was poor functional outcome,defined as a modified Rankin Scale score≥3 at 90 days,evaluated with the logistic regression analysis adjusted for age,sex and other clinical features.Results Among the 420 patients(mean age 63 years;74.3%male),CS was observed in 250(59.5%)following EVT.Logistic regression analysis showed that CS was strongly associated with poor functional outcomes.At 3 months,the proportion of patients with functional dependence was significantly higher in the CS group(76.8%)compared with the non-CS group(62.4%).In addition,the CS group exhibited a higher death rate compared with the non-CS group(p=0.028).Our study found that CS in the pons,as well as larger and denser staining volumes,was often indicative of poor prognosis.Conclusion In around half of AIS patients with EVT,CS can be observed and independently associate with poor clinical outcomes,primarily related to the location and density of CS.
基金funded by Key R&D Program of China(2017YFC1308204)This study was funded by Key R&D Program of China(2017YFC1308204),。
文摘Objective Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications,particularly for the drug tenecteplase.Therefore,we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment(IVT)in patients with acute ischaemic stroke(AIS).Methods A post hoc analysis of a randomised controlled trial(ClinicalTrials gov.NCT04797013)was conducted.Participants who received IVT with tenecteplase and alteplase(0.25 and 0.9 mg/kg,respectively)within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows:(1)≥90 mL/min/1.73 m2,normal renal function;(2)60-89 mL/min/1.73 m2,mildly decreased renal function;and(3)<60 mL/min/1.73 m2,moderately to severely decreased renal function.Patients stratified based on the normal renal function were used as the references.The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage(sICH)occurrence within 36 hours,respectively.Results In intravenous tenecteplase-treated patients,mildly decreased renal function(OR 3.10;95%CI:1.41 to 6.78)and moderately to severely decreased renal function(OR:8.03;95%CI:2.76 to 23.38)showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function.Among patients administered intravenous alteplase,those with a moderate-to severe decrease in renal function exhibited an elevated risk of sICH(adjusted OR:10.01;95%CI:1.61 to 62.15)and all-cause mortality(adjusted OR:4.54;95%CI:1.48 to 13.91).Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.Conclusions A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.
文摘Background Mechanical thrombectomy(MT)improves outcomes in patients who had an acute ischaemic stroke due to large vessel occlusion(LVO).However,socioeconomic status(SES)can influence recovery and prognosis.This study investigated the effect of SES,assessed via the Index of Multiple Deprivation(IMD),on MT outcomes in a multicentre London cohort.Methods This retrospective study included patients with anterior circulation LVO treated with MT between 2021 and 2023 at three London hospitals.Patients were grouped into IMD1-5(more deprived)and IMD6-10(less deprived).Inverse probability weighting balanced baseline characteristics.Primary outcomes were 90-day functional independence(modified Rankin Scale(mRS)0-2)and 90-day mRS shift.Secondary outcomes included recanalisation,early neurological changes,90-day mortality,symptomatic intracerebral haemorrhage(sICH)and haemorrhagic transformation(HT).Subgroup analyses explored interactions between IMD and demographic or clinical factors.LASSO(Least Absolute Shrinkage and Selection Operator)regression identified predictors of functional independence,while receiver operating characteristic analysis evaluated IMD’s predictive value.Results Among 1219 patients with acute LVO ischemic stroke treated with MT,533(43.7%)were in IMD1-5 and 686(56.3%)in IMD6-10.IMD1-5 patients had lower odds of functional independence at 90 days(RR 0.79,95%CI 0.70 to 0.90)and worse mRS shift(OR 1.29,95%CI 1.06 to 1.58).They also had higher risks of sICH(RR 2.07,95%CI 1.54 to 2.67)and HT(Risk Ratio 1.47,95%CI 1.21 to 1.80).Subgroup analysis highlighted IMD’s predictive importance in Asian or mixed ethnicity groups.A model incorporating IMD,age,sex,hypertension and National Institutes of Health Stroke Scale(area under the curve 0.656)demonstrated predictive accuracy for 90-day functional independence.Conclusions Lower SES correlates with worse outcomes and higher complications post-MT,even within a universal healthcare system.Addressing SES disparities could improve stroke care equity.
基金funded by Beijing Municipal Science&Technology Committee(Z211100003521019)China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical(Guangzhou)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029)National Natural Science Foundation(82111530203,82171272).
文摘Background The benefit-risk profile of tenecteplase in the elderly patients with acute ischaemic stroke(AIS)is uncertain.We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial,a randomised,phase 3,non-inferiority clinical trial.Disabling AIS patients aged≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale(mRS)score of 0-1 at 90 days.Symptomatic intracranial haemorrhage(sICH)within 36 hours was the safety outcome.Results Of 137 participants,mRS 0-1 at 90 days occurred in 37(49.3%)of 75 in the tenecteplase group vs 20(33.9%)of 59 in the alteplase group(risk ratio(RR)1.47,95%CI 0.96 to 2.23).sICH within 36 hours was observed in 3(4.0%)of 76 in the tenecteplase group and two(3.3%)of 61 in the alteplase group(RR 1.30,95%CI 0.20 to 8.41).Conclusions The risk-benefit profile of tenecteplase thrombolysis was preserved in the elderly patients,which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.
基金funded by the National Key R&D Program of China(2022YFC3501100).
文摘Background Previous studies have shown contradictory results between early application of antiplatelet therapy and intravenous thrombolysis(IVT)for mild acute ischaemic stroke(AIS),with National Institutes of Health Stroke Scale score 0-5.Objective To compare the benefits and risks of antiplatelet therapy and IVT in patients with mild AIS.Methods A systematic search of MEDLINE,Embase and Cochrane Library was conducted from database inception until July 2023,without language restriction.Randomised clinical trials(RCTs)or observational studies were selected.The primary outcomes were 90-day functional outcomes,measured by the modified Rankin Scale(mRS)score.The protocol has been registered before data collection.Results Two RCTs and four observational studies with relatively low risk of bias that enrolled 3975 patients were analysed(2454 in antiplatelet therapy and 1521 in IVT therapy).There were no significant differences between antiplatelet therapy and IVT in 90-day functional outcomes(mRS 0-1,OR 1.08(95%CI 0.73 to 1.58);mRS 0-2,OR,1.04(95%CI 0.63 to 1.73)),death(OR,0.64(95%CI 0.19 to 2.13))and stroke recurrence(OR,0.71(95%CI 0.28 to 1.79)).Antiplatelet therapy was associated with a reduced risk of symptomatic intracranial haemorrhage(sICH)compared with IVT(OR,0.20(95%CI 0.06 to 0.69)).Conclusions Among patients with mild AIS,compared with IVT,early application of antiplatelet therapy was not significantly associated with improved functional outcomes,reduced death or stroke recurrence,but was significantly associated with a reduced risk of sICH.
基金supported by grant funding from the Finnish Foundation for Cardiovascular Research sr,and the Finnish State research funding.
文摘Background Statins are essential for secondary prevention after ischaemic stroke(IS).However,statin intensity recommendations differ,and there is a concern about intracerebral haemorrhage(ICH).We studied the long-term impacts of initial statin intensity following IS.Methods Consecutive patients using high-intensity,moderate-intensity or low-intensity statin early after IS(n=45512)were retrospectively studied using national registries in Finland.Differences were adjusted using multivariable regression.The primary outcome was all-cause death within 12-year follow-up(median 5.9 years).Secondary outcomes were recurrent IS,cardiovascular death and ICH studied using competing risk analyses.Results High-intensity therapy was initially used by 16.0%,moderate-intensity by 73.8%and low-intensity by 10.2%.Risk of death was lower with high-intensity versus moderate-intensity(adjusted HR(adj.HR)0.92;95%CI 0.87 to 0.97;number needed to treat(NNT)32.0),with moderate-intensity versus low-intensity(adj.HR 0.91;95%CI 0.87 to 0.95;NNT 27.5)and with high-intensity versus low-intensity(adj.HR 0.83;95%CI 0.78 to 0.89;NNT 14.6)statin.There was a dose-dependent association of initial statin intensity with a lower probability of recurrent IS(p<0.0001)and cardiovascular death(p<0.0001).The occurrence of ICH was not associated with initial statin intensity(p=0.646).Conclusions Following IS,more intense initial statin treatment is associated with improved long-term outcomes but not with the risk of ICH.These findings emphasise the importance of high statin intensity shortly after IS.
文摘Background Stroke is a major cause of global mortality and disability.Currently,the treatment of acute ischaemic stroke through reperfusion has posed several challenges,raising the need for complementary options to protect the ischaemic penumbra.Recent investigations have indicated that certain epigenetic factors,specifically,histone deacetylases(HDACs)and sirtuins,can be promising for ischaemic stroke therapy,with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke.However,the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain.This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke.Methods This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke.The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Electronic searches will be conducted in PubMed,Web of Science and Scopus,with subsequent screening by independent reviewers based on the established eligibility criteria.Methodological quality will be evaluated using the SYRCLE risk of bias tool.The primary outcomes will be infarct volume and functional response,with the secondary outcomes established a priori.Data pertaining to infarct volume will be used for random-effects meta-analysis.Additionally,a descriptive summary will be conducted for the functional response and secondary outcomes.Discussion No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date.A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies.
基金supported by Beijing Municipal Science&Technology Commission(Z221100007422050)Capital's Funds for Health Improvement and Research(2020-1-2041,2022-2G 2049).
文摘Background GD-11,a novel brain cytoprotective drug,was designed to be actively taken up and transported across the blood-brain barrier via the glucose transporter.This study aimed to evaluate the safety and efficacy of GD-11 for improving the recovery of patients with acute ischaemic stroke(AIS).Methods A double-blind,randomised,placebo-controlled,phase 2 trial was conducted at 15 clinical sites in China.Patients aged 18-80 years with AIS within 48 hours were randomly assigned(1:1:1)to receive 160 mg GD-11,80 mg GD-11 and placebo,two times a day for 10 days.The primary endpoint was a modified Rankin Scale(mRS)score of 0-1 at 90 days after treatment.The safety outcome was any adverse events within 90 days.Results From 17 November 2022 to 22 March 2023,a total of 80 patients in the 160 mg GD-11 group,79 patients in the 80 mg GD-11 group and 80 patients in the placebo group were included.The proportion of an mRS score of 0-1 at day 90 was 77.5%in the 160 mg GD-11 group,72.2%in the 80 mg GD-11 group and 67.5%in the placebo group.Though no significant difference was found(p=0.3671),a numerically higher proportion was observed in the GD-11 group,especially in the 160 mg GD-11 group.The incidence of adverse events was similar across the three groups(p=0.1992).Conclusion GD-11 was safe and well-tolerated.A dosage of GD-11160 mg two times a day was recommended for a large trial to investigate the efficacy.
