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1.
Stroke Vasc Neurol ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296586

RESUMO

BACKGROUND: The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. METHODS: This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. RESULTS: Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min. CONCLUSIONS: In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

2.
J Neurointerv Surg ; 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37734930

RESUMO

BACKGROUND: Early endovascular intervention team mobilization may reduce reperfusion times and improve clinical outcomes for patients with acute ischemic stroke (AIS) with a possible intervenable vessel occlusion (IVO). In an emergency department or mobile stroke unit, incorporating rapidly available non-contrast CT (NCCT) information with examination findings may improve the accuracy of arterial occlusion prediction scales. For this purpose, we developed a rapid and straightforward IVO predictive instrument-the T3AM2PA1 scale. METHODS: The T3AM2PA1 scale was retrospectively derived from our 'Get with the Guidelines' database. We included all patients with acute stroke alert between January 2017 and August 2018 with a National Institutes of Health Stroke Scale (NIHSS) score between 5 and 25 inclusive. Different pre-intervention variables were collected, including itemized NIHSS and NCCT information. The T3AM2PA1 scale was also compared with other commonly used scales and was validated in a separate sequential retrospective cohort of patients with a full range of NIHSS scores. RESULTS: 574 eligible patients from 2115 acute stroke alerts were identified. The scale was established with five items (CT hyperdense sign, parenchymal hypodensity, lateralizing hemiparesis, gaze deviation, and language disturbance), with a total score of 9. To minimize unnecessary angiography, a cut-off of ≥5 for IVO detection yielded a sensitivity of 52%, a specificity of 90%, and a positive predictive value of 76%. CONCLUSIONS: The T3AM2PA1 scale accurately predicts the presence of clinical IVO in patients with AIS. Adopting the T3AM2PA1 scale could reduce revascularization times, improve treatment outcomes, and potentially reduce disability.

3.
JAMA Netw Open ; 6(6): e2316465, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37266940

RESUMO

Importance: Reperfusion therapy is the most effective treatment for acute ischemic stroke but remains underused in China. Objective: To evaluate the effect of a problem-oriented, culturally adapted, targeted quality improvement intervention on reperfusion therapy for patients with acute ischemic stroke in China. Design, Setting, and Participants: In this stepped-wedge cluster randomized clinical trial, patients from 16 secondary and 33 tertiary hospitals in China with acute ischemic stroke within 6 hours of symptom onset were consecutively recruited between July 1, 2018, and June 30, 2020. Interventions: Hospitals were randomly assigned to 1 of 3 sequences to receive the targeted quality improvement intervention (n = 5689), in which workflow reconstruction was promoted to reduce in-hospital reperfusion treatment delays, or usual care (n = 6443), in which conventional stroke care was left to the discretion of the stroke team. Main Outcomes and Measures: The primary outcome was the reperfusion therapy rate, a composite outcome of intravenous recombinant tissue plasminogen activator (IV rtPA) or endovascular thrombectomy (EVT) for eligible patients who arrived within 3.5 or 4.5 hours of symptom onset. Secondary outcomes were the IV rtPA administration rate among eligible patients who arrived within 3.5 hours of symptom onset, the EVT rate among eligible participants who arrived within 4.5 hours of symptom onset, the proportion of patients with door-to-needle time within 60 minutes, the proportion of patients with door-to-puncture time within 90 minutes, in-hospital mortality, and 3-month disability as measured by a modified Rankin Scale score greater than 2. Results: All 12 132 eligible patients (mean [SD] age, 66 [12.1] years; 7759 male [64.0%]) completed the trial. The reperfusion rate was 53.5% (3046 of 5689) for the eligible patients in the intervention period and 43.9% (2830 of 6443) in the control period. No significant improvement in primary outcomes was found for the intervention after adjusting for cluster, period, and imbalanced baseline covariates (adjusted risk difference [ARD], 5.5%; 95% CI, -8.0% to 19.0%; adjusted odds ratio [AOR], 1.26; 95% CI, 0.72-2.21) or for the secondary outcomes. However, significant improvements were found in secondary hospitals for reperfusion therapy (1081 of 1870 patients [57.8%] vs 945 of 2022 patients [42.9%]; ARD, 19.0%; 95% CI, 6.4%-31.6%; AOR, 2.24; 95% CI, 1.29-3.88), IV rtPA administration (1062 of 1826 patients [58.2%] vs 916 of 2170 patients [42.2%]; ARD, 20.3%; 95% CI, 7.4%-33.1%; AOR, 2.37; 95% CI, 1.34-4.19), and EVT (51 of 231 patients [22.1%] vs 37 of 259 patients [14.3%]; ARD, 13.6%; 95% CI, 1.0%-26.3%; AOR, 3.03; 95% CI, 1.11-8.25) in subgroup analyses. Conclusions and Relevance: In this stepped-wedge cluster randomized clinical trial of patients with acute ischemic stroke in China, the use of a targeted quality improvement intervention compared with usual care did not improve the reperfusion therapy rate. However, the intervention may be effective in secondary hospitals. Trial Registration: ClinicalTrials.gov Identifier: NCT03578107.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , AVC Isquêmico/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Melhoria de Qualidade , Reperfusão
4.
Stroke Vasc Neurol ; 8(1): 34-50, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35985768

RESUMO

BACKGROUND: Stroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015. METHODS: We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015. RESULTS: We analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend<0.001), and the prevalence of risk factors, including hypertension, diabetes, dyslipidaemia and current smoking, increased. The composite score of diagnostic tests for stroke aetiology assessment (from 0.22 to 0.36, Ptrend<0.001) and secondary prevention treatments (from 0.46 to 0.70, Ptrend<0.001) were improved. A temporal decrease was found in discharge against medical advice (DAMA) (from 15.2% (95% CI 13.7% to 16.7%) to 8.6% (8.1% to 9.0%); adjusted Ptrend=0.046), and decreases in in-hospital mortality (0.7% in 2015 vs 1.8% in 2005; adjusted OR (aOR) 0.52; 95% CI 0.32 to 0.85) and the composite outcome of in-hospital mortality or DAMA (8.4% in 2015 vs 13.9% in 2005; aOR 0.65; 95% CI 0.47 to 0.89) were observed. Disparities between rural and urban hospitals narrowed; however, disparities persisted in in-hospital management (brain MRI: rural-urban difference from -14.4% to -11.2%; cerebrovascular assessment: from -20.3% to -16.7%; clopidogrel: from -2.1% to -10.3%; anticoagulant for atrial fibrillation: from -10.9% to -8.2%) and in-hospital outcomes (DAMA: from 2.7% to 5.0%; composite outcome of in-hospital mortality or DAMA: from 2.4% to 4.6%). CONCLUSIONS: From 2005 to 2015, improvements in hospital admission and in-hospital management for ischaemic stroke in China were found. A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed. Disparities between rural and urban hospitals generally narrowed but persisted.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Estudos Transversais , Fatores de Risco , Hospitais Urbanos
5.
Clin Ther ; 44(5): 744-754, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35562205

RESUMO

PURPOSE: CN-105 is an IV, apolipoprotein E-mimetic pentapeptide. Preclinical studies have reported that CN-105 effectively down-regulates neuroinflammatory responses in microglia and mitigates neuronal excitotoxicity following acute brain injury. The CN-105 Phase I and II trials that have been done in the United States have demonstrated that CN-105 was well tolerated in US participants. Thus, the main objective of the present Phase I study was to investigate the tolerability and pharmacokinetic (PK) profiles of CN-105 in healthy Chinese participants. METHODS: This randomized, double-blind, placebo-controlled, dose-escalation study was performed in healthy participants using sequential 30-minute IV administration of single and multiple doses of CN-105 (four times daily for 13 doses). Forty volunteers were randomly assigned, in an 8:2 ratio, to one of four dosing groups, receiving either CN-105 (0.03, 0.1, 0.3, or 1 mg/kg), or placebo. Serial blood samples were collected for the measurement of plasma concentrations of CN-105. Tolerability was also assessed. FINDINGS: After single-dose administration, the plasma CN-105 concentration rapidly reached the peak by the end of infusion. The mean elimination half-life of CN-105 ranged from 2.3 to 3.6 hours. During single- and multiple-dosing paradigms, exposure to CN-105 (AUC) exhibited linear dependency on dose. Steady state was reached by the fourth dose, with minimal accumulation. The PK properties of CN-105 with single and multiple dosing were comparable to those observed in US participants. CN-105 was generally well tolerated in Chinese participants. A total of 13 adverse events were reported in 30% of subjects (12/40) at the 0.03 mg/kg (6/8), 0.1 mg/kg (1/8), 0.3 mg/kg (2/8), 1 mg/kg (0/8) doses and with placebo (3/8). All adverse events were mild or moderate in severity and self-limited, with no dose relationship observed. IMPLICATIONS: CN-105 was well tolerated in these healthy Chinese participants at doses of 0.1 to 1 mg/kg with single and multiple IV administrations. The PK characteristics of CN-105 were comparable among Chinese and Western subjects. A Phase II study in patients with intracranial hemorrhage is being planned in China. CLINICALTRIALS: gov identifiers: NCT02670824 and NCT03168581; Chinese Clinical Trial Registration identifier: CTR20202397.


Assuntos
Povo Asiático , Administração Oral , Área Sob a Curva , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , Humanos
6.
Stroke Vasc Neurol ; 7(4): 276-284, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35256525

RESUMO

BACKGROUND AND PURPOSE: Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA). This study aimed to investigate the association between baseline low-density lipoprotein cholesterol (LDL-C) level, lipid-lowering treatment and short-term risk of new stroke in patients with a minor ischaemic stroke or TIA. METHODS: We derived data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial. Patients with a minor stroke or TIA were categorised by LDL-C level at baseline (<2.6 or ≥2.6 mmol/L (100 mg/dL)) and with or without lipid-lowering treatment after symptom onset. The primary outcome was a new ischaemic stroke at 3 months. The association of baseline LDL-C level, lowering treatment and outcomes were assessed. RESULTS: Among 3027 patients, 2154 (71.2%) patients had an initial LDL-C ≥2.6 mmol/L, of which 1267 (41.9%) received lipid-lowering treatment. Elevated LDL-C level was associated with a higher risk of new ischaemic stroke at 3 months in patients without lipid-lowering treatment (adj.HR=1.35, 95% CI: 1.19 to 1.53), but not in those with lipid-lowering treatment (adj.HR=0.99, 95% CI: 0.82 to 1.19) (p for interaction=0.007). Patients with LDL-C ≥2.6 mmol/L had a numerically higher risk of ischaemic stroke (11.8% vs 8.0%, adj.HR=1.37, 95% CI: 0.96 to 1.96) in those without lipid-lowering treatment. For patients with LDL-C ≥2.6 mmol/L, lipid-lowering treatment was associated with reduced risk of ischaemic stroke at 3 months (7.9% vs 11.8%; adj.HR=0.54, 95% CI: 0.39 to 0.75). CONCLUSIONS: Elevated untreated baseline LDL-C level was associated with an increased short-term risk of ischaemic stroke among patients presenting with minor ischaemic stroke or TIA. There was potential benefit of lipid-lowering treatment in minor stroke or TIA patients with LDL-C ≥2.6 mmol/L. TRIAL REGISTRATION NUMBER: NCT00979589.


Assuntos
Isquemia Encefálica , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Infarto Cerebral , LDL-Colesterol , Clopidogrel , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/tratamento farmacológico , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia
7.
JAMA Netw Open ; 4(8): e2120745, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34387677

RESUMO

Importance: Stroke represents a significant burden on the health care system of China. The Chinese Stroke Center Alliance was launched in 2015 to monitor and improve care quality and outcomes for patients with acute stroke and transient ischemic attack (TIA). Objective: To evaluate the clinical characteristics, management, and in-hospital clinical outcomes and complications among patients with stroke or TIA in China. Design, Setting, and Participants: This quality improvement study assessed stroke or TIA admissions to 1476 participating hospitals in the Chinese Stroke Center Alliance between August 1, 2015, and July 31, 2019. Exposures: Stroke types and calendar year. Main Outcomes and Measures: Eleven guideline-based admission or discharge management measures and 2 summary measures: an all-or-none binary outcome and a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) for adherence to evidence-based stroke and TIA care and in-hospital clinical outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), including ischemic stroke, hemorrhagic stroke, TIA, or myocardial infarction; and in-hospital complications. Results: Of 1 006 798 patients with stroke or TIA (mean [SD] age, 65.7 [12.2] years; 383 500 [38.1%] female), 838 229 (83.3%) had an ischemic stroke, 64 929 (6.4%) had TIA, 85 705 (8.5%) had intracerebral hemorrhage (ICH), and 11 241 (1.1%) had subarachnoid hemorrhage (SAH). Management measures varied by cerebrovascular event type, with the mean (SD) composite score ranging from 0.57 (0.31) in SAH to 0.83 (0.24) in TIA. Poor outcomes and complications were highest among patients with SAH (21.9%; 95% CI, 21.0%-22.8% in-hospital death or DAMA; 9.6%; 95% CI, 9.1%-10.2% MACEs; and 31.4%; 95% CI, 30.6%-32.3% in-hospital complications) and patients with ICH (17.2%; 95% CI, 16.9%-17.5% in-hospital death or DAMA; 9.3%; 95% CI, 9.1%-9.5% MACEs; and 31.3%; 95% CI, 31.0%-31.6% in-hospital complications), followed by patients with ischemic stroke (6.1%; 95% CI, 6.0%-6.1% in-hospital death or DAMA; 6.3%; 95% CI, 6.3%-6.4% MACEs; and 12.8%; 95% CI, 12.7%-12.9% in-hospital complications), and lowest in patients with TIA (5.0%; 95% CI, 4.8%-5.2% in-hospital death or DAMA; 2.4%; 95% CI, 2.3%-2.5% MACEs; and 0.8%; 95% CI, 0.7%-0.8% in-hospital complications). Temporal improvements in management measures were observed from 2015 to 2019, especially in administration of intravenous recombinant tissue plasminogen activator (+60.3% relatively; 95% CI, 52.9%-70.5%), dysphagia screening (+14.7% relatively; 95% CI, 14.0%-15.6%), and use of anticoagulants for atrial fibrillation (+31.4% relatively; 95% CI, 25.7%-37.3%). Temporal improvements in in-hospital death or DAMA (-9.7% relatively; 95% CI, -9.6% to -8.5%) and complications (-27.1% relatively; 95% CI, -28.6% to -25.3) were also observed. Conclusions and Relevance: In this quality improvement study, performance measure adherence and poor outcomes and complications varied by cerebrovascular event type; although there were substantial improvements over time, these results suggest that support for the use of evidence-based practices is needed.


Assuntos
Ataque Isquêmico Transitório/terapia , Melhoria de Qualidade , Acidente Vascular Cerebral/terapia , Idoso , China/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/mortalidade , Masculino , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade
8.
Neurology ; 96(1): e1-e9, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33093222

RESUMO

OBJECTIVE: To investigate the association between protease-activated receptor-1 (PAR-1) gene F2R polymorphisms and efficacy of clopidogrel for minor stroke or TIA. METHODS: Three single nucleotide polymorphisms (CYP2C19*2 [681G>A, rs4244285], CYP2C19*3 [636G>A, rs4986893], and F2R [IVSn-14 A/T, rs168753]) were genotyped among 2,924 patients randomized to clopidogrel plus aspirin (n = 1,461) or aspirin alone (n = 1,463). The primary efficacy outcome was new stroke (ischemic or hemorrhagic) and the safety outcome was any bleeding. RESULTS: Overall, 859 (29.4%) were AA homozygotes, 1,479 (50.6%) were AT heterozygotes, and 586 (20.0%) were TT homozygotes for F2R IVSn-14 polymorphisms; 1,716 (58.7%) were carriers of at least 1 CYP2C19 loss-of-function allele (*2 or *3). Compared with aspirin alone, patients with clopidogrel-aspirin treatment had a low risk of new stroke in patients with AT genotype (7.6% vs 11.3%; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89) and TT genotype (5.8% vs 11.6%; HR, 0.46; 95% CI, 0.25-0.82) but not in carriers of the AA genotype (10.8% vs 11.6%; HR, 0.95; 95% CI, 0.63-1.44) (p = 0.03 for interaction). The association between F2R IVSn-14 A/T polymorphism and clopidogrel response was present regardless of the carrier status of the CYP2C19 loss-of-function alleles. The F2R IVSn-14 genotypes were not associated with the risk of any bleeding for clopidogrel-aspirin treatment (p = 0.66 for interaction). CONCLUSIONS: Among patients with minor ischemic stroke or TIA who were receiving clopidogrel and aspirin, those carrying the F2R IVSn-14 T allele had a lower rate of recurrent stroke than those who were not. CLINICALTRIALSGOV IDENTIFIER: NCT00979589.


Assuntos
Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Receptor PAR-1/genética , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Método Duplo-Cego , Feminino , Genótipo , Humanos , Ataque Isquêmico Transitório/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Acidente Vascular Cerebral/genética , Resultado do Tratamento
9.
Stroke ; 51(8): 2395-2403, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32586226

RESUMO

BACKGROUND AND PURPOSE: Infection occurs commonly in patients with acute ischemic stroke. We aimed to investigate the association of infection with short- and long-term risk of recurrent stroke in patients with ischemic stroke. METHODS: Data were derived from ischemic stroke patients in 2 stroke registries: the CSCA (Chinese Stroke Center Alliance) program recorded medical data during hospitalization, and the CNSR-III (Third China National Stroke Registry) recorded the medical data during hospitalization and finished 1-year follow-up. Associations of infection (pneumonia or urinary tract infection) during hospitalization with recurrent stroke in short (during hospitalization) and long term (since 30 days to 1 year after stroke onset) were analyzed. Short-term outcomes were analyzed with logistic models and long-term outcomes with Cox models. RESULTS: In the CSCA (n=789 596), the incidence of infection during hospitalization reached 9.6%. Patients with infection had a higher risk of stroke recurrence during hospitalization compared with patients without infection (10.4% versus 5.2%; adjusted odds ratio, 1.70 [95% CI, 1.65-1.75]; P<0.0001). In the CNSR-III (n=13 549), the incidence of infection during hospitalization was 6.5%. Infection during hospitalization was significantly associated with short-term risk of recurrent stroke (7.4% versus 3.9%; adjusted odds ratio, 1.40 [95% CI, 1.05-1.86]; P=0.02) but not with long-term risk of recurrent stroke (7.2% versus 5.2%; adjusted hazard ratio, 1.16 [95% CI, 0.88-1.52]; P=0.30). CONCLUSIONS: Infection was an independent risk factor for high risk of early stroke recurrence during hospitalization, but we have not found its sustained effect on long-term recurrent risk in patients with acute ischemic stroke.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Fatores de Risco
10.
Biomed Rep ; 11(6): 235-240, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798868

RESUMO

Since 3-n-butylphthalide (NBP) was approved by the China Food and Drug Administration for the treatment of acute ischemia stroke in 2002, a number of studies have investigated NBP worldwide. In recent years, NBP has also demonstrated potential as treatment of several neurodegenerative diseases, which has increased the interest in its mechanisms of protection and action. Clinical studies and studies that used cell or animal models, have directly demonstrated neuroprotective effects of NBP via the following mechanisms: i) Inhibiting the inflammatory reaction; ii) reducing mitochondrial oxidative stress; iii) regulating apoptosis and autophagy; iv) inducing resistance to endoplasmic reticulum stress; and v) decreasing abnormal protein deposition. Therefore, NBP may be a potential drug for neurodegenerative diseases, and it is particularly important to identify the mechanism of NBP as it may assist with the development of new drugs for neurodegeneration. The present review summarizes the neuroprotective mechanisms of NBP and discusses new perspectives and prospects. The aim of the current review is to provide a new summary regarding NBP and its associated mechanisms.

11.
Ann Neurol ; 86(3): 419-426, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31237713

RESUMO

OBJECTIVE: Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin has been suggested by American Heart Association/American Stroke Association guidelines for minor stroke (MS) and transient ischemic attack (TIA) patients. The purpose of this study was to find the potential subgroups that benefit from DAT. We aimed to compare the efficacy of clopidogrel-aspirin therapy with that of aspirin therapy in MS/TIA patients stratified by CYP2C19 genotype and risk profiles. METHODS: CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with LoFA of either *2 or *3. Low- and high-risk profile was defined as Essen Stroke Risk Score (ESRS) <3 and ≥3, respectively. Stroke recurrence at 1 year was considered primary outcome. RESULTS: Of a total 2,933 MS/TIA patients, there were 1,726 (58.8%) LoFA carriers and 1,068 (36.4%) patients at high risk (ESRS ≥3). No significant difference for stroke recurrence between the clopidogrel-aspirin group and aspirin alone group was found in LoFA carriers (11.2% vs 13.3%, hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.64~1.09). In stratified analyses by CYP2C19 genotype and ESRS, HRs (95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 1.00 (0.70~1.42), 0.63 (0.41~0.97), 0.62 (0.40~0.96), and 0.52 (0.31~0.88) among subgroups of LoFA carriers at low risk, LoFA carriers at high risk, LoFA noncarriers at low risk, and LoFA noncarriers at high risk, respectively, with p = 0.021 for interaction. INTERPRETATION: Overall, LoFA carriers do not benefit from DAT, but there is significant benefit for LoFA carriers who are at high risk. The benefit of clopidogrel in Chinese MS/TIA patients depends on CYP2C19 genotype and risk profile. ANN NEUROL 2019;86:419-426.


Assuntos
Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Ataque Isquêmico Transitório/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Alelos , Aspirina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Resultado do Tratamento
12.
Transl Stroke Res ; 10(5): 460-474, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30793257

RESUMO

The current literature indicates carotid endarterectomy (CEA) as the preferred treatment for symptomatic, moderate to severe carotid artery stenosis. However, recommendations for the management of acute tandem stenosis and complete occlusion, as well as postintervention restenosis of the carotid artery, remain controversial. Here, we review the literature evaluating these conditions and provide suggestions for clinical decision-making. Acute tandem stenosis or occlusion of the common and internal carotid arteries may be treated with angioplasty alone, reserving carotid artery stenting (CAS) or CEA for severe and complex cases. Patients who underwent CEA and developed ipsilateral restenosis may be subjected to angioplasty followed by CAS, which carries a lower risk of cranial nerve injury and subsequent restenosis of the artery. For post-CAS restenosis, current evidence recommends angioplasty and CAS for the management of moderate stenosis and CEA for severe stenosis of the carotid artery. Given the lack of level 1 evidence for the management of these conditions, the abovementioned recommendations may assist clinical decision-making; however, each case and its unique risks and benefits need to be assessed individually. Future studies evaluating and defining the risks and benefits of specific treatment strategies, such as CEA and CAS, in patients with acute tandem stenosis, occlusion, and postintervention restenosis of the carotid artery need to be conducted.


Assuntos
Angioplastia/métodos , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/métodos , Estenose das Carótidas/fisiopatologia , Humanos , Recidiva , Stents , Resultado do Tratamento
13.
Interv Neuroradiol ; 25(3): 330-334, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30409051

RESUMO

Treatment options for aneurysmal bone cysts include intralesional curettage, segmental excision, en bloc resection and endovascular embolization. The most commonly used treatment is intralesional curettage and selective arterial embolization is normally an adjunctive therapy, not a definitive treatment. We report a case of a C1 lateral mass aneurysmal bone cyst treated with a single session of endovascular embolization. Long-term follow up demonstrated complete resolution of the cyst. A study of aneurysmal bone cyst embolization was conducted and the key points for obtaining maximal devascularization of the cyst along with embolic material and technique are discussed.


Assuntos
Cistos Ósseos Aneurismáticos/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Doenças da Coluna Vertebral/cirurgia , Adulto , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
World Neurosurg ; 122: 282-286, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30415047

RESUMO

BACKGROUND: Iatrogenic vertebral artery injury is an uncommon but well recognized complication during cervical spine surgery. Intraoperative surgical repair is extremely challenging, and options for endovascular repair are limited because of the lack of proper equipment in the operating room setting. CASE DESCRIPTION: A 53-year-old woman who presented with myelopathy underwent anterior cervical diskectomy and fusion of C3-7. A significant laceration injury of the left vertebral artery was encountered during surgery, which was salvaged by intraoperative endovascular repair with a covered stent under portable fluoroscopy guidance. The salvage and repair led to the rest of the surgery being finished as planned preoperatively without any consequences. CONCLUSIONS: Vertebral artery injury is an uncommon but severe complication of cervical spine surgery. For uncontrolled bleeding, intraoperative endovascular repair with portable fluoroscopy is warranted and possible. A covered stent can seal the laceration and stop the bleeding completely which enables completion of the surgery.


Assuntos
Perda Sanguínea Cirúrgica , Complicações Intraoperatórias/cirurgia , Stents Metálicos Autoexpansíveis , Artéria Vertebral/lesões , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Feminino , Hemostasia Cirúrgica/métodos , Humanos , Doença Iatrogênica , Degeneração do Disco Intervertebral/cirurgia , Complicações Intraoperatórias/etiologia , Lacerações/etiologia , Lacerações/cirurgia , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Doenças da Medula Espinal/cirurgia , Resultado do Tratamento
15.
J Am Heart Assoc ; 7(20): e010623, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371291

RESUMO

Background Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.4±5.6 versus median 4 [1-10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330-3209] versus 644 [142-2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door-to-needle time median 95 [72-112] versus 62 [49-85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door-to-needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.


Assuntos
Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Distribuição por Idade , Idoso , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etnologia , China/epidemiologia , China/etnologia , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Qualidade da Assistência à Saúde , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etnologia , Estados Unidos/epidemiologia , Estados Unidos/etnologia
16.
Stroke Vasc Neurol ; 2(4): 176-183, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29507777

RESUMO

Objective: Many patients receiving dual antiplatelet therapy still had recurrent strokes. We aimed to identify factors associated with recurrent stroke at 90 days in patients receiving dual antiplatelet therapy in Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial. Methods: Patients with transient ischaemic attack or minor stroke receiving clopidogrel and aspirin in the trial were analysed in the study. The primary outcome was recurrent stroke within 90 days after the index event. Cox proportional hazard model with backward selection was used to identify factors associated with stroke. Results: Among 2584 patients, 212 (8.2%) had a recurrent stroke, 216 (8.4%) had a composite of stroke, myocardial infarction, or vascular death and 204 (7.9%) had ischaemic stroke within 90 days. Multivariate analysis identified the following factors associated with stroke: history of hypertension with poor blood pressure control (HR, 1.92; 95% CI 1.22 to 3.03), the high baseline National Institute of Health Stroke Scale (NIHSS) score of 2 and 3 (2.12 (1.07 to 4.21) and 4.11 (2.05 to 8.22), respectively), time from onset to randomisation of <12 hours (1.47 (1.12 to 1.94)), the lipid-lowering therapy (0.61 (0.47 to 0.83)), the open-label aspirin dose at day 1 of ≥300 mg (1.98 (1.45 to 2.69)). Intracranial arterial stenosis (ICAS) was significantly associated with stroke in the sensitivity analysis (2.17 (1.16 to 4.04)). Conclusions: The high baseline NIHSS score, hypertension with poor blood pressure control, ICAS, time from onset to randomisation of less than 12 hours and no lipid-lowering therapy were associated with stroke, suggesting that patients with identified predictors still remain to be at high risk of recurrent stroke although being under the dual antiplatelet therapy. Trial registration number: http://clinicaltrials.gov/show/NCT00979589. ClinicalTrials.gov number: NCT00979589.


Assuntos
Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Terapia Antiplaquetária Dupla , Ataque Isquêmico Transitório/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Prevenção Secundária , Idoso , Aspirina/efeitos adversos , China , Clopidogrel/efeitos adversos , Método Duplo-Cego , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/mortalidade , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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