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BACKGROUND AND PURPOSE: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion. METHODS: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days. RESULTS: In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30-14.48] and 3.20 [1.68-6.09]; respectively) and lower mortality (60.8% versus 77.6%, P=0.005 and 35.0% versus 66.2%, P<0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94-1.02]). CONCLUSIONS: Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT. Registration: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800014759.
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Artéria Basilar/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Idoso , Arteriopatias Oclusivas/complicações , Procedimentos Endovasculares/métodos , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Prognóstico , Estudos Prospectivos , Sistema de Registros , Trombectomia/métodos , Resultado do Tratamento , Insuficiência Vertebrobasilar/complicaçõesRESUMO
Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.
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Fibrinolíticos/administração & dosagem , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Trombectomia , Ativador de Plasminogênio Tecidual/administração & dosagem , Doença Aguda , Idoso , Hemorragia Cerebral/etiologia , Terapia Combinada , Procedimentos Endovasculares , Feminino , Fibrinolíticos/efeitos adversos , Estado Funcional , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Trombectomia/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversosRESUMO
OBJECTIVE: Our objective is to investigate the safety and long-term efficacy of the Wingspan stent (Boston Scientific, Natick, MA, USA) for treating severe atherosclerotic stenosis of the middle cerebral artery (MCA). METHODS: A total of 278 consecutive patients from our stroke database with clinical symptoms within the prior 90 days and intracranial atherosclerotic stenosis of 70% or above of the MCA were enrolled in this study between September 2012 and November 2014, and these patients were followed until the end of June 2015. The endpoint events included any stroke or death within 30 days after stenting and any subsequent ipsilateral ischemic stroke. RESULTS: Among the 278 enrolled patients, 277 patients (99.6%) successfully underwent stenting. The mean rate of stenosis decreased from 82.5 ± 7.9% to 9.0 ± 3.2% following treatment. Within 30 days after stenting, 12 patients (4.3%) experienced endpoint events, including 8 cases (2.9%) of hemorrhagic stroke and 4 cases (1.4%) of ischemic stroke; 2 perioperative deaths occurred. During 8-33 months of follow-up, 19 patients developed endpoint events. The 1- and 2-year endpoint event rates were 5.8% (95% confidence interval [CI], 5.0%-15.7%) and 7.2% (95% CI, 4.3%-10.1%), respectively. CONCLUSIONS: From this study, we can conclude that the treatment of severe symptomatic atherosclerotic stenosis of the MCA using the Wingspan stent was safe and effective and that the long-term stroke recurrence rate after stenting was low.
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Arteriopatias Oclusivas/terapia , Procedimentos Endovasculares/instrumentação , Arteriosclerose Intracraniana/terapia , Artéria Cerebral Média , Stents , Idoso , Angiografia Digital , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/mortalidade , Isquemia Encefálica/etiologia , Angiografia Cerebral/métodos , Constrição Patológica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/mortalidade , Hemorragias Intracranianas/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiopatologia , Desenho de Prótese , Recidiva , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The operation of the Cansolv tail gas treatment device in natural gas plants generates acidic and alkaline wastewater from the venturi unit and amine purification unit (APU), respectively. The APU wastewater is complex in composition and contains hard-to-degrade organic matter, which can adversely impact the normal functioning of the water treatment system. This study assesses the efficacy of three ozone-based advanced oxidation processes (ozone (O3), ozone/hydrogen peroxide (O3/H2O2), and ozone/Fenton (O3/Fenton)) for treating Cansolv wastewater, with chemical oxygen demand (COD) and total organic carbon (TOC) serving as indicators of organic degradation. The findings demonstrate that all three processes effectively eliminate coloration and reducible sulfur, with O3/Fenton exhibiting superior performance in removing organic substances. The treated wastewater has a clarified light-yellow appearance with residual COD levels at 43 mg L-1. Under the optimum Fenton oxidation conditions (initial pH 5, H2O2 dosage 97.8 mmol L-1, FeSO4·7H2O dosage 550 mg L-1), average TOC and COD removal rates reached 50% and 97%, respectively. After a treatment duration of 60 minutes, the wastewater demonstrated an enhanced membrane-specific flux, confirming the effectiveness of the O3/Fenton oxidation process in mitigating membrane fouling while ensuring the stable operation of the wastewater treatment system.
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Identification of cytotoxic T lymphocyte (CTL) epitopes from additional tumor antigens is essential for the development of specific immunotherapy of malignant tumors. Neuritin, a recently discovered antigen overexpressed in astrocytoma, is considered to be a promising target for biological therapy. In the present study, we predicted and identified HLA-A2-restricted CTL epitopes from neuritin by using the following four-step procedure: (1) computer-based epitope prediction from the amino acid sequence of neuritin; (2) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A2.1 molecule; (3) stimulation of primary T cell response against the predicted peptides in vitro; and (4) testing of the induced CTLs toward target cells expressing neuritin and HLA-A2.1. The results demonstrated that effectors induced by peptides of neuritin containing residues 13-21, 121-129 and 4-12 could specifically-secrete interferon-γ and lyse target cells. Our results indicate that these peptides are new HLA-A2.1-restricted CTL epitopes, and may serve as valuable tools for astrocytoma immunotherapy.
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Epitopos/metabolismo , Antígeno HLA-A2/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Sítios de Ligação de Anticorpos/efeitos dos fármacos , Sítios de Ligação de Anticorpos/genética , Linhagem Celular Tumoral , Células Dendríticas/fisiologia , Relação Dose-Resposta a Droga , Proteínas Ligadas por GPI/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interferon gama/metabolismo , Camundongos , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Peptídeos/farmacologiaRESUMO
SEVs (small extracellular vesicles) contents signatures appear to mirror pathological changes of diseases, and mapping sEVs contents profile is a promising approach for non-invasive diagnosis of the disease. Herein, we propose a universal system for accurately and damage-freely mapping of sEVs content profile using dual-recognition triggered CHA (catalytic hairpin assembly) and DNAzyme based signal amplification strategy. After immunoassay based capture of CD63 positive sEVs by anti-CD63 lgG coated on the surface of polystyrene plates, probes are incubated with fixed sEVs to penetrate sEVs membrane and act to sense sEVs contents. In detection step, integrated CHA and DNAzyme based strategy is initiated by released initiator from capture probe after recognizing targets, forming a dual circle signal recycling process, realizing signal amplification for high sensitivity. Given the attractive analytical features that i) a universal platform for indistinctive sEVs nucleic acids and protein molecules detection; ii) high sensitivity derived from dual circle signal recycling process; iii) enzyme-free characteristic of integrated CHA and DNAzyme minimizes the interference to sEVs biological activity; iv) mapping of sEVs contents profiles indicates a brand-new strategy for non-invasive diagnosis of the disease, the present approach shows great promise for analyzing additional different analytes in clinical and experimental researches.
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Técnicas Biossensoriais , DNA Catalítico , Vesículas Extracelulares , DNA Catalítico/metabolismo , Poliestirenos , CatáliseRESUMO
BACKGROUND: The drug 3-n-butylphthalide (NBP) was developed and approved in China, where it has been used to treat ischemic cerebrovascular diseases. It is also considered to have a neuroprotective effect. This study aimed to evaluate whether NBP combined with endovascular treatment (EVT) can improve the clinical outcome and safety in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: Data from three studies of patients treated with EVT for AIS due to LVO were combined in this study. Patients of LVO undergoing EVT were dichotomized into NBP and non-NBP subgroups. The primary efficacy outcome was the shift of the modified Rankin Scale (mRS) score at 90 days. The secondary efficacy outcome included favorable functional outcomes, functional independence, and excellent outcome (defined as an mRS score of 3 or less) at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h. RESULTS: A total of 1820 patients undergoing EVT were included in this study; 628 (37.5%) patients received NBP treatment, whereas 1138 (62.5%) did not. After adjusting for multiple factors, NBP was associated with the improvement of functional outcomes at 90 days (adjusted common odds ratio [OR]: 1.503; 95% confidence interval (CI): 1.254-1.801; p < 0.001). NBP was associated with a higher rate of 90-day favorable outcomes (adjusted OR: 1.589; 95% CI: 1.251-2.020; p < 0.001) and a lower rate of 90-day mortality (adjusted OR: 0.486 [95% CI: 0.372-0.635]; p < 0.001). sICH occurred in 74 of 682 (10.9%) patients in the NBP group and 155 of 1126 (13.8%) patients in the non-NBP group; no statistical difference was detected (adjusted OR: 0.787 [95% CI: 0.567-1.092]; p = 0.152). CONCLUSION: Among patients with AIS due to LVO, NBP combined with EVT is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Estudos Retrospectivos , Hemorragias Intracranianas , TrombectomiaRESUMO
Background: Percutaneous transluminal angioplasty and stenting with the Wingspan stent has proven safe and effective in patients with middle cerebral artery stenosis (MCAS), but the off-label use of the Neuroform stent might be an alternative treatment. This study aimed to compare the safety and effectiveness of the above two intracranial stents in patients with MCAS. Methods: We retrospectively analyzed consecutive patients with symptomatic MCAS who had been treated with the Neuroform EZ or the Wingspan stent. A propensity score was generated to control for differences in baseline characteristics. The endpoints were the rate of peri-procedural complications within 30 days after stenting, the in-stent restenosis rate, and any target-vessel-related stroke or deaths during follow-up. Results: After matching for propensity score, the peri-procedural complication rate in the Wingspan group was 7.4% compared with 5.6% in the Neuroform group (p = 1.00), while the follow-up in-stent restenosis rates were 23.3 vs. 14.3%, respectively (p = 0.41). In the restenosis group, the patients tended to be younger (p < 0.01) and the degree of artery stenosis before stenting was higher (p < 0.01). Conclusion: This study indicated that in patients with symptomatic MCAS, Neuroform EZ stents are an alternative to Wingspan. Moreover, younger age and higher degree of artery stenosis before stenting might be a risk factor of in-stent restenosis.
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BACKGROUND: Eight randomized controlled trials have consistently shown that endovascular treatment plus best medical treatment improves outcome after acute anterior proximal intracranial large vessel occlusion strokes. Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation, large vessel occlusion is of any additional benefits remains unclear. OBJECTIVE: This study compares the safety and efficacy of direct endovascular treatment versus intravenous recombinant tissue-type plasminogen activator bridging with endovascular treatment (bridging therapy) in acute stroke patients with intracranial internal carotid artery or middle cerebral artery-M1 occlusion within 4.5 h of symptom onset. METHODS AND DESIGN: The DEVT study is a randomized, controlled, multicenter trial with blinded outcome assessment. This trial uses a five-look group-sequential non-inferiority design. Up to 194 patients in each interim analysis will be consecutively randomized to direct endovascular treatment or bridging therapy group in 1:1 ratio over three years from about 30 hospitals in China. OUTCOMES: The primary end-point is the proportion of independent neurological function defined as modified Rankin scale score of 0 to 2 at 90 days. The primary safety measure is symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days. TRIAL REGISTRY NUMBER: ChiCTR-IOR-17013568 (www.chictr.org.cn).
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Acidente Vascular Cerebral , Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
PURPOSE: To investigate the combined effect of olfactory ensheathing cell (OEC) transplantation and recombinant human glial cell line-derived neurotrophic factor (rhGDNF) intravitreal injection on optic nerve functional recovery following incomplete injury in adult rats. METHODS: The optic nerves of adult rats were crushed by forceps and then GDNF was injected into vitreous cavity, OECs transplanted into injured optic nerve, or GDNF vitreous injection combined with OECs transplantation, and balanced salt solution was injected into vitreous cavity of control group rats respectively. Flash visual evoked potential (F-VEP) was performed on the injured eye immediately after injury and at 1, 2, 4, and 8 weeks after injury. RESULTS: The F-VEP waveforms were almost silent immediately after the optic nerve injury. The latency of the F-VEP (LP1) recovered nearly to the normal value 1 week after injury in the treatment groups. The amplitude recovered more slowly. It recovered more obviously and rapidly in the rhGDNF combined with OEC group. At 8 weeks after injury, the amplitude was restored to 64.5% of the pre-injury level in the control group and to 91.8% in the GDNF+OEC treatment group. Wheat germ agglutinin (WGA) labeling showed retinal ganglion cell (RGC) axon regeneration and prolongation in the combined group, and the regenerated axons extended across the traumatized area and reached the distal end of the injured optic nerve. CONCLUSIONS: The combination of OEC transplantation and rhGDNF intravitreal injection will be more effective in promoting the recovery of visual function after incomplete injury of the optic nerve in adult rats.
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Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Mucosa Olfatória/citologia , Mucosa Olfatória/transplante , Traumatismos do Nervo Óptico/tratamento farmacológico , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Células Cultivadas , Potenciais Evocados Visuais/efeitos dos fármacos , Imunofluorescência , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Humanos , Injeções Intravítreas , Masculino , Mucosa Olfatória/efeitos dos fármacos , Traumatismos do Nervo Óptico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Aglutininas do Germe de Trigo/metabolismoRESUMO
INTRODUCTION: Excessive neuroinflammation aggravates the brain injury caused by intracerebral hemorrhage (ICH), while the upstream mechanisms that initiate neuroinflammation remain unclear. Toll-like receptor 4 (TLR4) signaling is important to trigger inflammatory responses in ICH, and cold-inducible RNA-binding protein (CIRP) has been shown as a novel ligand of TLR4 by recent studies. However, whether the CIRP could trigger the neuroinflammation via activating TLR4 signaling in ICH still needs to be investigated. METHODS: Human serum CIRP levels were measured using the ELISA kits. Western blot, FJB staining, brain water content, and neurological deficit scores were used to investigate the roles of CIRP in brain injury caused by ICH. RESULT: First, we found increased CIRP levels in the blood of patients with ICH when compared to the control individuals, and the ICH patients with mRS > 2 have higher serum CIRP levels in contrast to those with mRS ≤ 2. In the ICH mice, we also found that brain CIRP protein and mRNA levels were also increased after ICH. Furthermore, using the CIRP-/- mice, we found that CIRP-/- mice had less brain damages showing in less FJB+ cells, reduced brain water content (BWC) and lower neurological deficit scores (NDS) compared to that in WT mice after ICH. Cytokines including IL-6, TNF-α, and IL-1ß from CIRP-/- mice were attenuated after ICH. CIRP-/- mice also exhibited reduced TLR4 expression which was accompanied by the decreased activity of NF-κB. This suggests that TLR4 signaling might be involved in CIRP-mediated inflammatory injury possibly via NF-κB activation after ICH. CONCLUSION: Our findings suggest that CIRP may activate TLR4 signaling, and further inducing NF-κB activation to increase the expression levels of cytokines and aggravate inflammatory injury in ICH. Targeting CIRP may be a promising strategy for ICH treatment.
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Lesões Encefálicas , Receptor 4 Toll-Like , Animais , Hemorragia Cerebral/complicações , Humanos , Inflamação , Camundongos , NF-kappa B/metabolismo , Proteínas de Ligação a RNA , Transdução de Sinais , Receptor 4 Toll-Like/genéticaRESUMO
PURPOSE: To evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation. METHODS: Consecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared. RESULTS: A total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups. CONCLUSIONS: RS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT.
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Transtornos Cerebrovasculares/terapia , Pontuação de Propensão , Stents , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Idoso , Transtornos Cerebrovasculares/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Trombectomia/tendências , Resultado do TratamentoRESUMO
BACKGROUND: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. METHODS: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. FINDINGS: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. INTERPRETATION: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. FUNDING: Jiangsu Provincial Special Program of Medical Science.
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Procedimentos Endovasculares/métodos , Insuficiência Vertebrobasilar/terapia , Idoso , Artérias/fisiologia , Isquemia Encefálica/complicações , China , Procedimentos Endovasculares/efeitos adversos , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Resultado do Tratamento , Insuficiência Vertebrobasilar/mortalidadeRESUMO
PURPOSE: To study the association of the enhancement ratio (ER) of aneurysmal wall enhancement (AWE) with symptomatic intracranial aneurysms (IAs), we hypothesized that the ER of AWE would be stronger in symptomatic IAs than in asymptomatic IAs, as assessed by high-resolution magnetic resonance imaging (HRMRI). MATERIALS AND METHODS: Between February 2016 and February 2018, 80 consecutive patients with 89 unruptured IAs were reviewed. Patients and IAs were divided into symptomatic and asymptomatic groups. In addition to the clinical characteristics, the IA features (e.g., size, shape) were evaluated via computed tomography angiography, while the ER and enhanced patterns were evaluated by HRMRI. Multiple logistic regression analysis was performed to determine the independent risk factors for symptomatic IAs. Receiver operating characteristic curve analysis was used for the final model to obtain the optimal thresholds. RESULTS: Multiple logistic regression analysis indicated that only the ER was associated with symptomatic IAs. The threshold value of the ER was 60.5%. CONCLUSIONS: A higher ER was more frequently identified in symptomatic IAs. More attention should be paid to this factor in the management of IAs.
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Aneurisma Intracraniano/patologia , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
This retrospective study is to investigate the safety and efficacy of the stent implanting for treating severe symptomatic atherosclerotic stenosis of the intracranial vertebrobasilar artery (ICVBA). 213 patients who had undergone intervention for severe symptomatic ICVBA stenosis between September 2012 to May 2018 were enrolled into this study. Among the 213 enrolled patients, 210 patients (98.6%) obtained successfully revascularization and 206 patients (96.7%) had good revascularization after stenting. The extent of stenosis before and after intervention was 86.3⯱â¯6.8% and 9.1⯱â¯3.7%, respectively. Within 90â¯days after stenting, 10 patients (4.7%) experienced primary endpoint events, including 4 cases (4.2%) in the intracranial vertebral artery (V4) group and 6 (5.1%) in basilar artery (BA) group. Among them, 2 (2.1%) and 3 cases (2.5%) of ischemic stroke in V4 and BA group, respectively; and 2 (2.1%) and 2 (1.7%) cases of TIA in V4 and BA group, respectively. One (0.8%) case in the BA group dead because of the acute stent occlusion resulted in the top of the basilar syndrome. Six patients (2.8%) experienced adverse events, including 2 (2.1%) and 4 (3.4%) cases of groin hematoma in the V4 and BA group, respectively. No cases of hemorrhagic stroke, stent dislocation and vessel dissection in both groups. Our study showed that a low complication rate and a high and good revascularization rate would be achieved by the treatment of severe symptomatic atherosclerotic stenosis of the ICVBA using the stents.
Assuntos
Angioplastia/efeitos adversos , Hemorragias Intracranianas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Stents/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Insuficiência Vertebrobasilar/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Aterosclerose/cirurgia , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Insuficiência Vertebrobasilar/etiologiaRESUMO
OBJECTIVES: To evaluate the risk factors for rupture of intracranial aneurysms (IAs) using high resolution MRI (HRMRI). METHODS: 91 consecutive patients with 106 IAs were reviewed from February 2016 to April 2017. Patients and IAs were divided into ruptured and unruptured groups. In addition to the clinical characteristics of the patients, the features of IAs (eg, shape) were evaluated by CT angiography, whereas wall thickness, enhanced patterns, and enhancement ratio (ER) were evaluated by MRI. Multiple logistic regression analysis was used to identify independent risk factors associated with the rupture of IAs. Receiver operating characteristic curve analysis was performed on the final model, and the optimal thresholds were obtained. RESULTS: ER (OR 6.638) and partial wall enhancement (PWE) (OR 6.710) were not markers of aneurysms more prone to rupture, but simply were more commonly found in the ruptured aneurysm cohort. The threshold value for ER was 61.5%. CONCLUSIONS: ER (≥61.5%) and IAs with PWE are better predictors of rupture. Increased attentions should be paid to these factors during assessment of IA rupture.
Assuntos
Aneurisma Roto/diagnóstico por imagem , Endotélio Vascular/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Estudos de Coortes , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Cerebral hemorrhage is a serious complication of intracranial artery stenting that could be fatal without timely identification and treatment. Prompt brain CT scan would help to evaluate whether cerebral hemorrhage occurs, however, the diverse features of the CT scan immediately after stenting could influence the judgement sometimes. Therefore, we analyzed and summarized these features to help to determine the clinical significance of these CT features. The prompt CT features after stenting were classified into three types. Type I indicates that no high-density shadows. Type II indicates that high-density shadows scattered in the infarct areas and/or subarachnoid spaces without mass effect. Type III indicates high-density shadows scattered in and/or out of the infarct areas and/or subarachnoid space with obvious mass effects. Based on this classification, the patients in both Type I and II would continue the double anti-platelet treatment (DAPT) and anti-coagulation treatment, while the later need closer monitoring. However, patients in Type III must immediately withdraw the DAPT and anti-coagulation treatment with close monitoring and surgical intervention was needed when necessary. Nineteen (3.79%) patients were classified into Type III, and 5 (1.00%) of the 19 were accepted surgical intervention. Two of these patients died (0.40%). The prompt CT scan timely distinguishing the cerebral hemorrhage was necessary after intracranial artery stent angioplasty. Additionally, based on the different prompt CT features to take different therapeutic strategies after stenting would achieve better outcomes for ischemic stroke or transient ischemic stroke (TIA) patients underwent intracranial artery endovascular therapy.
RESUMO
AIM: To study the effect of antiparallel phosphorothioate triplex-forming oligonucleotide (apsTFO) matching with the shear stress response element (SSRE) of tissue factor (TF) gene promoter region on the expression of TF in endothelial cells (ECs) of rat common carotid artery stenosis. METHODS: The model of common carotid artery middle segment stenosis was established by silica gel pipe loop ligation in SD rats. The mRNA expression and protein synthesis of TF, early growth response-1 (Egr-1) and specificity protein 1 (Sp1) were measured by in situ hybridization (ISH) and immunohistochemistry (IHC) technique. GT21-apsTFO, GT20-apsTFO, GT20-psTFO and FITC-labeled apsTFO, matching with the SSRE of TF gene promoter region, were designed, and intravenously injected into rats at 0.5 h before operation. TFO was detected 4 h after the operation, and the mRNA expression and protein synthesis of TF, Egr-1 and Sp1 were detected 6 h after the operation. RESULTS: There were much fluorescence in vascular tissue, especially in the nuclear of ECs 4.5 h after the injection of apsTFO. The mRNA expression and protein synthesis of TF reduced by 22% - 23% with injection of GT20-apsTFO 6.5 h after stenosis (P < 0.01) and by 10% - 11% with GT21-apsTFO at the same time (P < 0.05). The inhibition by GT20-apsTFO was stronger than that of the GT21-apsTFO (P < 0.05). The expression of TF was not inhibited by the GT20-psTFO (P > 0.05). The mRNA expression and protein synthesis of Egr-1 and Sp1 did not change in the rat treated with GT20-apsTFO, GT20-psTFO and GT21-apsTFO (P > 0.05). CONCLUSION: apsTFO could mero-inhibit the expression of TF gene but could not change the expression of Egr-1 and Sp1 protein.
Assuntos
Células Endoteliais/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Oligonucleotídeos/farmacologia , Tromboplastina/genética , Animais , Estenose das Carótidas/genética , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Imuno-Histoquímica , Hibridização In Situ , Masculino , Oligonucleotídeos/síntese química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Resistência ao Cisalhamento , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Estresse Mecânico , Tromboplastina/metabolismoRESUMO
OBJECTIVE: To report the postmortem findings of a case of highly pathogenic H5N1 avian influenza virus occurring in human beings. METHODS: Postmortem examination was carried out in a deceased caused by highly pathogenic H5N1 avian influenza virus. Detailed light microscopy of major organs, including heart, lungs, liver, spleen, kidneys and brain, was performed. The lung tissue was further investigated by histochemistry, immunohistochemistry and electron microscopy. RESULTS: Major histopathologic changes in lungs secondary to highly pathogenic H5N1 avian influenza virus included diffuse alveolar damage, hyaline membrane formation and focal hemorrhage. Some of the alveolar spaces contained lightly eosinophilic liquid, lymphocytes, macrophages, plasma cells and small number of neutrophils. Congested capillaries were commonly seen in the alveolar septa which were focally rimmed by hyaline membrane. Immunohistochemical study showed that the lymphocytes were mainly of T lineage and macrophages were also demonstrated. CONCLUSIONS: Highly pathogenic H5N1 avian influenza virus causes pathologic changes mostly in lungs, including diffuse alveolar damage and acute exudative changes (involving mainly T lymphocytes and macrophages). The resulting parenchymal destruction, consolidation, pulmonary edema and hemorrhage eventually lead to respiratory distress and death.
Assuntos
Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Humana/patologia , Pulmão/patologia , Adulto , Autopsia , Complexo CD3/análise , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Influenza Humana/metabolismo , Influenza Humana/virologia , Antígenos Comuns de Leucócito/análise , Pulmão/ultraestrutura , Pulmão/virologia , Microscopia EletrônicaRESUMO
The CYP2C19 gene plays a detrimental role in the metabolism of clopidogrel. This study aimed to investigate the association between CYP2C19 polymorphisms and the clinical efficacy of clopidogrel therapy in patients who have undergone carotid artery stenting (CAS). CYP2C19 genotype screening was performed on 959 ischemic stroke patients. Of these patients, 241 who had undergone CAS were enrolled in the study. They were all followed up for 1 year after stent surgery, and the primary clinical end-points were ischemic events. The frequencies of the CYP2C19*2 and *3 alleles among the 959 patients were 31.80% and 5.06%, respectively. Regarding the 241 participants who had undergone CAS, multivariate Cox regression analysis showed that the CYP2C19 loss-of-function (LOF) alleles (*2 and *3) were risk factors for post-CAS prognosis. Within 1 year of follow-up, the patients carrying the CYP2C19 LOF alleles were more likely to experience ischemic events than those carrying none. The occurrence of ischemic events did not significantly differ between the *2 and *3 allele carriers. Our results suggest that CYP2C19 LOF alleles (*2 and *3) significantly impact the prognosis of patients on clopidogrel therapy after CAS and that the CYP2C19*2 and CYP2C19*3 alleles have the same effects on prognosis.