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1.
J Cereb Blood Flow Metab ; : 271678X241238033, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459953

RESUMO

The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.

2.
J Neurointerv Surg ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538054

RESUMO

BACKGROUND: Despite the remarkable effectiveness of endovascular treatment (EVT), recent randomized controlled trials indicate that up to half of patients with large core infarction have a very poor outcome (modified Rankin Scale score 5-6 at 90 days). This study investigates the combined effect of Alberta Stroke Program Early CT Score (ASPECTS) and age on very poor outcome in patients with large core infarction treated with EVT. METHODS: This subanalysis of the MAGIC registry, which is a prospective, multicenter cohort study of early treatment in acute stroke, focused on patients with ASPECTS ≤5 presenting within 24 hours of stroke onset and receiving CT followed by EVT from November 1, 2021 to February 8, 2023. Multivariable logistic regression was used to investigate the independent and joint association of ASPECTS and age with very poor outcome. RESULTS: Among the 490 patients (57.3% men; median (IQR) age 69 (59-78) years), very poor outcome occurred more frequently in those with lower ASPECTS (65.2% in ASPECTS 0-2 vs 43.4% in ASPECTS 3-5; P<0.001). The predictive value of successful recanalization for very poor outcome was significant in patients with ASPECTS 3-5 (P=0.010), but it diminished in those with ASPECTS 0-2 (P=0.547). Compared with patients with ASPECTS 3-5 and age ≤69 years, the risk of a very poor outcome increased incrementally in those with lower ASPECTS, advanced age, or both (P<0.05). Graphical plot analysis showed a significantly lower probability of very poor outcome in younger patients (≤69 years) compared with older patients (>69 years) across all ASPECTS points. CONCLUSION: These findings suggest prioritizing young patients as candidates for EVT in those with ASPECTS 0-2.

3.
JAMA ; 331(10): 840-849, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38329440

RESUMO

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Idoso , Método Duplo-Cego , Trombectomia/efeitos adversos , Hemorragias Intracranianas , Metilprednisolona/efeitos adversos
4.
BMC Neurol ; 24(1): 24, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216864

RESUMO

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).


Assuntos
Procedimentos Endovasculares , Hiperglicemia , Acidente Vascular Cerebral , Humanos , Artéria Basilar , Hemoglobinas Glicadas , Glucose , Hospitalização , Resultado do Tratamento , Trombectomia
5.
J Neurointerv Surg ; 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37665653

RESUMO

BACKGROUND: Endovascular treatment (EVT) is a well-established approach for acute ischemic stroke. Whether bridging intravenous thrombolysis (IVT) before EVT confers any benefits remains uncertain. The objective of the study was to compare the efficacy and safety of direct EVT with or without bridging IVT in patients with acute basilar artery occlusion (BAO). METHODS: This multicenter cohort study enrolled 647 patients with acute BAO who underwent either bridging IVT before EVT or direct EVT from the BASILAR registry. The primary outcome was an independent functional outcome measured by the modified Rankin Scale (mRS) score of 0-2. Secondary outcomes included excellent functional outcome (mRS 0-1), favorable functional outcome (mRS 0-3), and mortality rate at 90 days, as well as symptomatic intracranial hemorrhage (sICH), and successful reperfusion between the two treatment groups. RESULTS: Direct EVT and bridging IVT before EVT exhibited similar primary outcomes (27.3% vs 27.7%, respectively) and distributions of mRS scores at 90 days. Moreover, rates of sICH and 90-day mortality were not significantly different between the two groups (7.3% vs 6.0%, adjusted OR (aOR) 0.79, 95% CI 0.34 to 1.86, P=0.84 for sICH; 46.8% vs 43.7%, aOR 0.86, 95% CI 0.54 to 1.38, P=0.53 for mortality). CONCLUSIONS: Among patients with acute BAO, functional outcomes were similar between those treated with bridging IVT before EVT and those treated with direct EVT, and there was no difference between the two groups in terms of sICH and mortality rates.

6.
Ann Clin Transl Neurol ; 10(11): 2043-2052, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37649303

RESUMO

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Tirofibana/efeitos adversos , Fibrinolíticos , Resultado do Tratamento , Hemorragias Intracranianas/induzido quimicamente , Artérias , Reperfusão/efeitos adversos
7.
J Neurosurg ; 139(6): 1715-1721, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310068

RESUMO

OBJECTIVE: Authors of this study aimed to evaluate the effects of collateral status on the prognostic value of endovascular treatment (EVT) in patients with basilar artery occlusion (BAO) due to large-artery atherosclerosis (LAA). METHODS: The study included 312 patients from the BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry who had undergone EVT for acute BAO due to LAA and whose composite collateral scores were available. The effects of collateral status on EVT were assessed based on the composite collateral score (0-2 vs 3-5). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. RESULTS: The composite collateral score was 0-2 in 130 patients and 3-5 in 182. A good collateral status (composite collateral score 3-5) was associated with a favorable outcome (66/182 [36.3%] vs 31/130 [23.8%], adjusted odds ratio [aOR] 2.21, 95% CI 1.18-4.14, p = 0.014). A lower baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent predictor of a favorable outcome in the poor collateral status group (aOR 0.91, 95% CI 0.87-0.96, p = 0.001). In the good collateral status group, there was a significant correlation between favorable outcomes and a younger age (aOR 0.96, 95% CI 0.92-0.99, p = 0.016), lower baseline NIHSS score (aOR 0.89, 95% CI 0.85-0.93, p < 0.001), lower proportion of diabetes mellitus (aOR 0.31, 95% CI 0.13-0.75, p = 0.009), and shorter procedure time (aOR 0.99, 95% CI 0.98-1.00, p = 0.003). CONCLUSIONS: A good collateral status was a strong prognostic factor after EVT in patients with BAO underlying LAA. A shorter procedure time was associated with favorable outcomes in patients with a good collateral status.


Assuntos
Arteriopatias Oclusivas , Aterosclerose , Procedimentos Endovasculares , Acidente Vascular Cerebral , Insuficiência Vertebrobasilar , Humanos , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/cirurgia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/cirurgia , Aterosclerose/complicações , Aterosclerose/cirurgia , Trombectomia/métodos , Acidente Vascular Cerebral/etiologia
8.
Neurology ; 101(3): e253-e266, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37202165

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated the association between the procedure time (PT) and outcomes for patients with proximal large vessel occlusion; however, whether the relationship remains for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the association between PT and other procedure-related variables on clinical outcomes among patients with ABAO who underwent endovascular treatment (EVT). METHODS: Patients with ABAO who underwent EVT with a documented PT in the EVT for Acute Basilar Artery Occlusion (BASILAR) study from January 2014 to May 2019 among 47 comprehensive centers in China were included. Multivariable analysis was performed to reveal the association between PT and 90-day modified Rankin Scale score, mortality, complications, and all-cause death at 1 year. RESULTS: Of the 829 patients from the BASILAR registry, 633 eligible patients were included. Longer PT were associated with a lower rate of favorable outcome (by 30 minutes, adjusted OR 0.82 [95% CI 0.72-0.93], p = 0.01). In addition, a PT ≤ 75 minutes was associated with a favorable outcome (adjusted OR 2.03 [95% CI 1.26-3.28]). The risk of complications and mortality increased by 0.5% and 1.5% with every 10 minutes increase in PT, respectively (R2 = 0.64 and R2 = 0.68, p < 0.01). The cumulative rates of favorable outcomes and successful recanalization plateaued after 120 minutes (2 attempts). Restricted cubic spline regression analysis for the probability of favorable outcomes had an L-shape association (p nonlinearity = 0.01) with PT with significant benefit loss before 120 minutes and then appeared relatively flat. DISCUSSION: For patients with ABAO, procedures that exceeded 75 minutes were associated with an increased risk of mortality and lower odds of a favorable outcome. A careful assessment of futility and the risks of continuing the procedure should be made after 120 minutes.


Assuntos
Arteriopatias Oclusivas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Artéria Basilar , Arteriopatias Oclusivas/terapia , Embolectomia , Trombectomia/métodos , Acidente Vascular Cerebral/terapia , Estudos Retrospectivos
9.
CNS Neurosci Ther ; 29(8): 2162-2170, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36914967

RESUMO

AIMS: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and clinical outcomes at 90 days in acute ischemic stroke due to large vessel occlusion receiving endovascular treatment. METHODS: The RESCUE BT trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial, consisting of 948 stroke patients from 55 centers in China. A total of 542 patients with glucose and glycated hemoglobin (HbA1C) values at admission were included in this analysis. SHR, measured by glucose/HbA1C, was evaluated as both a tri-categorical variable (≤1.07 vs. 1.08-1.29 vs. ≥1.30) and a continuous variable. The primary outcome was a favorable functional outcome (modified Rankin Scale [mRS] score ≤2) at 90 days. The secondary outcome included excellent functional outcome (mRS score ≤1) and safety outcomes, such as 90-day mortality and intracranial hemorrhage. The study was registered with Chictr.org.cn (ChiCTR-INR-17014167). RESULTS: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving favorable functional outcome of mRS score of 0-2 (adjusted odds ratio, 0.44; 95% confidence interval, 0.28-0.69; p < 0.001) and excellent clinical outcome of mRS score of 0-1 (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.79; p = 0.004) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for preexisting diabetes and Alberta Stroke Program Early Computed Tomography Score (ASPECTS). CONCLUSION: Stress hyperglycemia ratio, as measured by the glucose/HbA1C, was associated with a decreased odds of achieving a favorable functional outcome in patients with acute large vessel occlusion stroke at 90 days.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Hiperglicemia , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Hemoglobinas Glicadas , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Hiperglicemia/complicações , Glucose , Trombectomia/métodos
10.
Brain Behav Immun ; 107: 330-344, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371010

RESUMO

BACKGROUND: Stroke is a major cause of morbidity and mortality worldwide. After cerebral ischemia, peripheral immune cells infiltrate the brain and elicit an inflammatory response. However, it is not clear when and how these peripheral immune cells affect the central inflammatory response, and whether interventions that target these processes can alleviate ischemia-reperfusion (I/R) injury. METHODS: Single-cell transcriptomic sequencing and bioinformatics analysis were performed on peripheral blood of mice at different times after I/R to analyze the key molecule of cell subsets. Then, the expression pattern of this molecule was determined through various biological experiments, including quantitative RT-PCR, western blot, ELISA, and in situ hybridization. Next, the function of this molecule was assessed using knockout mice and the corresponding inhibitor. RESULTS: Single-cell transcriptomic sequencing revealed that peripheral monocyte subpopulations increased significantly after I/R. Cathepsin S (Ctss)was identified as a key molecule regulating monocyte activation by pseudotime trajectory analysis and gene function analysis. Next, Cathepsin S was confirmed to be expressed in monocytes with the highest expression level 3 days after I/R. Infarct size (p < 0.05), neurological function scores (p < 0.05), and apoptosis and vascular leakage rates were significantly reduced after Ctss knockout. In addition, CTSS destroyed the blood-brain barrier (BBB) by binding to junctional adhesion molecule (JAM) family proteins to cause their degradation. CONCLUSIONS: Cathepsin S inhibition attenuated cerebral I/R injury; therefore, cathepsin S can be used as a novel target for drug intervention after stroke.


Assuntos
Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Camundongos , Monócitos , Catepsinas , Traumatismo por Reperfusão/genética , Análise de Sequência de RNA
11.
Front Aging Neurosci ; 14: 885707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663583

RESUMO

Stroke is a major cause of morbidity and mortality worldwide. In the early stages of stroke, irreversible damage to neurons leads to high mortality and disability rates in patients. However, there are still no effective prevention and treatment measures for the resulting massive neuronal death in clinical practice. Astrocyte reprogramming has recently attracted much attention as an avenue for increasing neurons in mice after cerebral ischemia. However, the field of astrocyte reprogramming has recently been mired in controversy due to reports questioning whether newborn neurons are derived from astrocyte transformation. To better understand the process and controversies of astrocyte reprogramming, this review introduces the method of astrocyte reprogramming and its application in stroke. By targeting key transcription factors or microRNAs, astrocytes in the mouse brain could be reprogrammed into functional neurons. Additionally, we summarize some of the current controversies over the lack of cell lineage tracing and single-cell sequencing experiments to provide evidence of gene expression profile changes throughout the process of astrocyte reprogramming. Finally, we present recent advances in cell lineage tracing and single-cell sequencing, suggesting that it is possible to characterize the entire process of astrocyte reprogramming by combining these techniques.

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