RESUMO
OBJECTIVES: It is unclear which selection strategy, plain CT vs. CT perfusion (CTP), is more powerful in predicting outcome after mechanical thrombectomy (MT). We aimed to compare the effect of plain CT and CTP in predicting outcome after MT within 6 h. METHODS: We conducted a prospective analysis of a retrospective cohort from our single-center study, which had occlusion of the internal carotid artery and middle cerebral artery up to the proximal M2 segment and received MT within 6 h. According to the Alberta Stroke Program Early CT Score (ASPECTS), patients were divided into a high-ASPECTS group (≥ 6) and a low ASPECTS group (< 6). Similarly, patients were divided into mismatch and no-mismatch groups according to the DEFUSE3 criteria for CTP. A good outcome was defined as a 90-day modified Rankin Scale (mRS) score of ≤ 3. Univariate and binary logistic regression analyses were used to investigate the association between different imaging modality and 90-day mRS score, and mortalities, respectively. RESULTS: The high ASPECTS group included 307 patients (89.2%). The mismatch group included 189 (54.9%) patients meeting the DEFUSE3 criterion. Compared to the low ASPECTS group, the high ASPECTS group had a good outcome (odds ratio (OR), 2.285; [95% confidence interval (CI) (1.106, 4.723)], p = 0.026) and lower mortality (OR, 0.350; [95% CI (0.163, 0.752)], p = 0.007). However, there were no significant differences in good outcomes and mortality between the mismatch and no-mismatch groups. CONCLUSIONS: Compared with plain CT, CTP does not provide additional benefits in the selection of patients suitable for MT within 6 h. CLINICAL RELEVANCE STATEMENT: CT perfusion is not superior to plain CT for the prediction of clinical outcomes when selecting patients for mechanical thrombectomy in the first 6 h. In that clinical setting, plain CT may be safe in the absence of perfusion data. KEY POINTS: ⢠The advantage of CT perfusion (CTP) over CT in pre-mechanical thrombectomy (MT) screening has not been proven for patients with a large infarct core. ⢠CTP is not better than plain CT in predicting good outcome following MT within 6 h. ⢠Plain CT is sufficient for selecting patients suitable for MT within 6 h of large artery occlusion.
Assuntos
Trombectomia , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Idoso , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Trombectomia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso de 80 Anos ou mais , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/cirurgia , Angiografia por Tomografia Computadorizada/métodos , Imagem de Perfusão/métodosRESUMO
OBJECTIVES: To investigate the association between baseline hemoglobin level and early neurologic deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation (CASE-â ¡, NCT04487340). Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy, and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis. RESULTS: A total of 8162 patients were included. Patients with END had lower baseline hemoglobin levels (136 and 140 g/L, P<0.01) and higher rates of anemia (24.2% and 16.9%, P<0.01) compared with non-END patients. Binary logistic regression analysis showed that baseline hemoglobin level (OR=0.995, 95%CI: 0.991-0.999, P<0.05) and anemia (OR=1.238, 95%CI: 1.055-1.454, P<0.01) were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients. Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients (P<0.01), although this relationship was only significant in male patients (P<0.05) and not in female patients (P>0.05). CONCLUSIONS: There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis, especially in male patients, in whom both lower and higher hemoglobin level may increase the risk of END.
Assuntos
Anemia , Hemoglobinas , AVC Isquêmico , Terapia Trombolítica , Humanos , Masculino , Feminino , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/sangue , Hemoglobinas/análise , Terapia Trombolítica/efeitos adversos , Anemia/etiologia , Anemia/tratamento farmacológico , Pessoa de Meia-Idade , Administração Intravenosa , Idoso , Modelos Logísticos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Fibrinolíticos/efeitos adversos , Isquemia Encefálica/tratamento farmacológicoRESUMO
High-performing n-type polymers are crucial for the advance of organic electronics field, however strong electron-deficient building blocks with optimized physicochemical properties for constructing them are still limited. The imide-functionalized polycyclic aromatic hydrocarbons (PAHs) with extended π-conjugated framework, high electron deficiency and good solubility serve as promising candidates for developing high-performance n-type polymers. Among the PAHs, phenanthrene (PhA) features a well-delocalized aromatic π-system with multiple modifiable active sites . However, the PhA-based imides are seldom studied, mainly attributed to the synthetic challenge. Herein, we report two functionalized PhAs, CPOI and CPCNI, by simultaneously incorporating imide with carbonyl or dicyanomethylene onto PhA. Notably, the dicyanomethylene-modified CPCNI exhibits a well stabilized LUMO energy level (-3.84â eV), attributed to the synergetic inductive effect from imide and cyano groups. Subsequently, based on CPOI and CPCNI, two polymers PCPOI-Tz and PCPCNI-Tz were developed. Applied to organic thin-film transistors, owing to the strong electron-deficiency of CPCNI, polymer PCPCNI-Tz shows an improved electron mobility and largely decreased threshold voltage compared with PCPOI-Tz. This work affords two structurally novel electron-deficient building blocks and highlights the effectiveness of dual functionalization of PhAs with strong electron-withdrawing groups for devising n-type polymers.
RESUMO
Developing high-performance but low-cost n-type polymers remains a significant challenge in the commercialization of organic field-effect transistors (OFETs). To achieve this objective, it is essential to design the key electron-deficient units with simple structures and facile preparation processes, which can facilitate the production of low-cost n-type polymers. Herein, by sequentially introducing fluorine and cyano functionalities onto trans-1,3-butadiene, we developed a series of structurally simple but highly electron-deficient building blocks, namely 1,4-dicyano-butadiene (CNDE), 3-fluoro-1,4-dicyano-butadiene (CNFDE), and 2,3-difluoro-1,4-dicyano-butadiene (CNDFDE), featuring a highly coplanar backbone and deep-positioned lowest unoccupied molecular orbital (LUMO) energy levels (-3.03-4.33â eV), which render them highly attractive for developing n-type semiconducting polymers. Notably, all these electron-deficient units can be easily accessed by a two-step high-yield synthetic procedure from low-cost raw materials, thus rendering them highly promising candidates for commercial applications. Upon polymerization with diketopyrrolopyrrole (DPP), three copolymers were developed that demonstrated unipolar n-type transport characteristics in OFETs with the highest electron mobility of >1â cm2 â V-1 s-1 . Hence, CNDE, CNFDE, and CNDFDE represent a class of novel, simple, and efficient electron-deficient units for constructing low-cost n-type polymers, thereby providing valuable insight for OFET applications.
RESUMO
BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Administração Intravenosa , Idoso , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodosRESUMO
BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.
RESUMO
The development of high-performance n-type polymer semiconductors is powered by the design and synthesis of electron-deficient building blocks with optimized physicochemical properties. By meticulously installing an imide group onto fluorene and its cyanated derivative, we report here two very electron-deficient building blocks, imide-functionalized fluorenone (FOI) and its cyanated derivative (FCNI), both featuring a deep-lying lowest unoccupied molecular orbital energy level down to -4.05â eV and highly coplanar framework, endowing them ideal units for constructing n-type polymers. Thus, a series of polymers are built from them, exhibiting unipolar n-type transport character with a highest electron mobility of 0.11â cm2 â V-1 s-1 . Hence, FOI and FCNI offer a remarkable platform for accessing high-performance n-type polymers and the imide functionalization of appropriate (hetero)arenes is a powerful strategy for developing polymers with deep-lying LUMOs for n-type organic electronics.
RESUMO
Intramolecular noncovalent interactions (INIs) have served as a powerful strategy for accessing organic semiconductors with enhanced charge transport properties. Herein, we apply the INI strategy for developing dopant-free hole-transporting materials (HTMs) by constructing two small-molecular HTMs featuring an INI-integrated backbone for high-performance perovskite solar cells (PVSCs). Upon incorporating noncovalent Sâ â â O interaction into their simple-structured backbones, the resulting HTMs, BTORA and BTORCNA, showed self-planarized backbones, tuned energy levels, enhanced thermal properties, appropriate film morphology, and effective defect passivation. More importantly, the high film crystallinity enables the materials with substantial hole mobilities, thus rendering them as promising dopant-free HTMs. Consequently, the BTORCNA-based inverted PVSCs delivered a power conversion efficiency of 21.10 % with encouraging long-term device stability, outperforming the devices based on BTRA without Sâ â â O interaction (18.40 %). This work offers a practical approach to designing charge transporting layers with high intrinsic mobilities for high-performance PVSCs.
RESUMO
Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to measure glymphatic function. We established modified index for diffusion tensor image analysis along the perivascular space (mALPS-index), which was calculated on diffusion tensor image (DTI), compared it with the classical detection of glymphatic clearance function calculated on Glymphatic MRI after intrathecal administration of gadolinium (study 1), and analyzed the relationship between CSVD imaging markers and mALPS-index in CSVD patients from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) (study 2). Among 39 patients included in study 1, mALPS-index were significantly related to glymphatic clearance function calculated on Glymphatic MRI ( r = -0.772~-0.844, p < 0.001). A total of 330 CSVD patients were included in study 2. Severer periventricular and deep white matter hyperintensities (ß = -0.332, p < 0.001; ß = -0.293, p < 0.001), number of lacunas (ß = -0.215, p < 0.001), number of microbleeds (ß = -0.152, p = 0.005), and severer enlarged perivascular spaces in basal ganglia (ß = -0.223, p < 0.001) were related to mALPS-index. Our results indicated that non-invasive mALPS-index might represent glymphatic clearance function, which could be applied in clinic in future. Glymphatic clearance function might play a role in the development of CSVD.
Assuntos
Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Sistema Glinfático/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagemRESUMO
Purpose To develop a quantitative assessment of collateral perfusion at CT and to investigate its value in the prediction of outcome in patients with acute ischemic stroke (AIS). Materials and Methods This retrospective study reviewed data from consecutive patients with AIS and an occluded M1 segment of the middle cerebral artery who underwent pretreatment perfusion CT between May 2009 and August 2017. The maximum cerebral blood flow (CBF) of collateral vessels (cCBFmax) within the Sylvian fissure was calculated for each patient. Good outcome was defined as a 90-day modified Rankin scale score of 0-2. Multivariable logistic regression analysis was used to determine the relationship between cCBFmax and (a) hemorrhagic transformation and (b) clinical outcome. Results The final analysis included 204 patients (median age, 73 years; interquartile range, 62-80 years; 82 [40.2%] women). Multivariable logistic regression analysis showed that higher cCBFmax was an independent predictor for (a) a lower risk of hemorrhagic transformation (odds ratio [OR], 0.99; 95% confidence interval [CI]: 0.98, 1.00; P = .009) after adjusting for baseline National Institutes of Health Stroke Scale (NIHSS), endovascular thrombectomy, baseline infarct core volume, and recanalization and (b) better outcome (OR, 1.02; 95% CI: 1.01, 1.03; P = .001) after adjusting for age, baseline NIHSS score, endovascular thrombectomy, hypertension, baseline infarct core volume, and recanalization, respectively. Conclusion The measurement of maximum cerebral blood flow of collateral vessels within the Sylvian fissure is a feasible quantitative collateral assessment at perfusion CT. Maximum cerebral blood flow of collateral vessels was associated with clinical outcome in patients with acute ischemic stroke. © RSNA, 2019 Online supplemental material is available for this article.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Circulação Colateral , Artéria Cerebral Média/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Meios de Contraste , Feminino , Humanos , Iopamidol , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. METHODS: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. RESULTS: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all P<0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all P>0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (OR=0.856, 95%CI:0.664-1.103, P>0.05). CONCLUSIONS: EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.
Assuntos
Isquemia Encefálica , Serviços Médicos de Emergência , Acidente Vascular Cerebral , Terapia Trombolítica , Administração Intravenosa , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. METHODS: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. RESULTS: Binary logistic regression showed that DNT (OR=0.994, 95%CI:0.991-0.997, P<0.01) or DRT (OR=0.989, 95%CI:0.983-0.995, P<0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. CONCLUSIONS: Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Terapia Trombolítica , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (n=101) and out-of-hospital stroke (n=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis. RESULTS: Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, P<0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, P<0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, P<0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, P<0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, P<0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, P<0.05], compared with patients in primary stroke center. Age (OR=0.934, 95%CI: 0.882-0.989, P<0.05) and baseline National Institute of Health Stroke Scale score (OR=0.912, 95%CI: 0.855-0.973, P<0.01) were independent risk factors for prognosis of in-hospital stroke patients. CONCLUSIONS: In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Administração Intravenosa , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hospitais/estatística & dados numéricos , Humanos , Prognóstico , Terapia Trombolítica/estatística & dados numéricos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. RESULTS: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all P>0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all P>0.05). CONCLUSIONS: The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Terapia Trombolítica , Isquemia Encefálica/tratamento farmacológico , Humanos , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Fatores de TempoRESUMO
Synaptic dysfunction and neuronal excitatory/inhibitory imbalance have been implicated in Alzheimer's disease (AD) pathogenesis. Although intensive studies have been focused on the excitatory synaptic system, much less is known concerning the mechanisms mediating inhibitory synaptic dysfunction in AD. We reported previously that protocadherin-γC5 (Pcdh-γC5), a member of clustered Pcdh-γ subfamily of cadherin-type synaptic adhesion proteins, functions to promote GABAergic synaptic transmission. We reveal here that Pcdh-γC5 is enriched in vesicular GABA transporter-positive synaptic puncta and its expression levels are increased in neuronal hyperexcitation conditions, upon ß-amyloid (Aß) treatment, and in amyloid precursor protein (APP)/presenilin-1 (PS1)-transgenic mice of both sexes. This is associated with elevated levels of GABAergic proteins and enhanced synaptic inhibition. Genetic knock-down experiments showed that Pcdh-γC5 modulates spontaneous synaptic currents and Aß-induced synaptic alterations directly. Our results support a model in which Pcdh-γC5 senses neuronal hyperexcitation to augment GABAergic inhibition. This adaptive mechanism may be dysregulated under chronic excitation conditions such as AD, leading to aberrant Pcdh-γC5 expression and associated synaptic dysfunction.SIGNIFICANCE STATEMENT Synaptic dysfunction is causal for Alzheimer's disease (AD). Here, we reveal a novel pathway that contributes GABAergic synaptic dysfunction in AD mediated by protocadherin-γC5. Our study not only identifies a new mechanism mediating excitatory/inhibitory balance in AD, but may also offer a new target for potential therapeutic intervention.
Assuntos
Doença de Alzheimer/fisiopatologia , Caderinas/metabolismo , Córtex Cerebral/fisiopatologia , Inibição Neural , Sinapses/metabolismo , Transmissão Sináptica , Animais , Proteínas Relacionadas a Caderinas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
BACKGROUND AND PURPOSE: This study aimed to evaluate the occurrence rate of the internal carotid artery pseudo-occlusion (ICA-PO) on 4-dimensional-computed tomography angiography and to investigate its relationship with clinical outcome after reperfusion therapy. METHODS: In this case-control study, we retrospectively reviewed our prospectively collected database for consecutive acute ischemic stroke patients who received reperfusion therapy between June 2009 and February 2017. ICA-PO was defined when the arterial segment was not opacified on peak arterial phase yet was subsequently patent after artery peak phase on 4-dimensional-computed tomography angiography. Poor outcome was defined as 3-month modified Rankin Scale of 4 to 6. Binary logistic regression was used to investigate the relationship of ICA-PO with poor outcome and the rate of reperfusion, respectively. RESULTS: A total of 143 patients with isolated middle cerebral artery occlusion were included and 30 (21.0%) had ICA-PO. Patients with ICA-PO were more likely to have poor outcome (80.0% versus 37.2%; P<0.001) and a lower rate of reperfusion (45.8% versus 69.0%; P=0.033) than those without. Binary logistic regression revealed that ICA-PO was independently associated with poor outcome (odds ratio, 7.957; 95% confidence interval, 1.655-34.869; P=0.009) and reperfusion at 24 hours (odds ratio, 0.150; 95% confidence interval, 0.045-0.500; P=0.002) after adjustment. Among patients with no reperfusion, all ICA-PO patients obtained poor outcome, whereas only 45.2% non-PO patients underwent poor outcome (P=0.001). CONCLUSIONS: Four dimensional-computed tomography angiography is a useful noninvasive technique to identify ICA-PO. Patients with ICA-PO are prone to undergo poor outcome from reperfusion therapy, especially when reperfusion is not achieved.
Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Procedimentos Endovasculares , Infarto da Artéria Cerebral Média/terapia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/epidemiologia , Estudos de Casos e Controles , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Infarto da Artéria Cerebral Média/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologiaRESUMO
Background and Purpose- Whether patients with small perfusion lesions benefit from thrombolysis remains an uncertainty. We assessed acute ischemic stroke patients with a total perfusion lesion of <15 mL and tested the hypothesis the pattern of corticospinal tract (CST) involvement might predict outcome in thrombolysis-eligible patients. Methods- We used a prospectively collected cohort of acute ischemic stroke patients being assessed for thrombolysis at 7 centers. Three neurologists categorized the presence of hypoperfusion and infarction within CST. Excellent outcome was defined as 90-day modified Rankin Scale score 0 to 1. Results- Of 2654 patients, 407 had a perfusion lesion <15 mL and were clinically eligible for thrombolysis (243 being treated). Median National Institutes of Health Stroke Scale was 5.0, and 312 (76.7%) patients achieved excellent outcome. Alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 72.0% versus untreated 83.5%; odds ratio, 0.541; P=0.025). For patients with CST hypoperfusion without CST infarction, alteplase treatment was an independent favorable factor for excellent outcome (alteplase-treated 75.6% versus untreated 47.1%; odds ratio, 4.096; P=0.045). Among patients with CST infarction, alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 30.6% versus untreated 88.9%; odds ratio, 0.002; P=0.003). Among patients without either CST hypoperfusion or CST infarction, alteplase treatment was not an independent influencing factor for excellent outcome (alteplase-treated 80.1% versus untreated 87.7%; P=0.258). Conclusions- Only patients with CST hypoperfusion without CST infarction among eligible acute ischemic stroke patients with small perfusion lesions could benefit from thrombolysis, which needs to be confirmed in future prospective studies. Patient selection, including an assessment of lesion location rather than purely lesion volume, may be ideal.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Tratos Piramidais/irrigação sanguínea , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Tratos Piramidais/diagnóstico por imagem , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Terapia Trombolítica , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the value of multi-segment clot (MSC) sign on dynamic CT angiography (CTA) in predicting recanalisation and outcome after reperfusion therapy in acute ischaemic stroke (AIS) with large artery occlusion (LAO). METHODS: We retrospectively reviewed data of anterior circulation LAO patients from a prospectively collected database for consecutive AIS patients who underwent perfusion CT (CTP) before treatment. MSC sign was defined as the presence of multiple segments on dynamic CTA derived from CTP data. Good outcome was defined as modified Rankin score 0-3 at 90 days. RESULTS: A total of 181 LAO patients were enrolled. MSC sign was present in 73 (40.3%) patients. When compared with patients without MSC sign, patients with MSC sign had a significantly higher rate of recanalisation (76.7% versus 56.5%, p = 0.005) and good outcome (67.1% versus 51.0%, p = 0.035). Multivariable logistic regression analyses showed that MSC sign was an independent predictor for both recanalisation (OR [95% CI] = 2.237 [1.069-4.681]; p = 0.033) and good outcome (OR [95% CI] = 2.715 [1.154-6.388]; p = 0.022) after adjustment. CONCLUSIONS: The MSC sign is a good indicator for recanalisation and good outcome after reperfusion therapy in anterior circulation LAO patients. KEY POINTS: ⢠MSC sign was present in about 40% acute anterior circulation LAO patients. ⢠MSC sign is a predictor for recanalisation after reperfusion treatment. ⢠Patients with MSC sign have a better outcome.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the value of collateral score based on CT perfusion (CTP-CS) in predicting the clinical outcome of patients with anterior circulation ischemic stroke after thrombectomy. METHODS: Clinical data of acute ischemic stroke patients with anterior artery occlusion undergoing endovascular treatment in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and October 2016 were retrospectively reviewed. Collateral scores were assessed based on CTP and digital subtraction angiography (DSA) images, respectively. And DSA-CS or CTP-CS 3-4 was defined as good collateral vessels. Good clinical outcome was defined as a modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke. The binary logistic regression model was used to analyze the correlation between the collateral score and clinical outcome, and the receiver operating characteristic (ROC) curve was used to analyze the value of DSA-CS and CTP-CS in predicting the clinical outcome. RESULTS: Among 40 patients, 33 (82.5%) acquired recanalization and 16 (40.0%) got good outcome. Compared with poor outcome group, the collateral score (all P<0.05) and the rate of good collateral vessels were higher in good outcome group (all P<0.01). After adjust baseline National Institute of Health Stroke Scale (NIHSS) and onset to recanalization time (ORT), good collateral vessels were independent factor of good outcome (CTP-CS:OR=48.404, 95% CI:1.373-1706.585, P<0.05; DSA-CS:OR=34.651, 95% CI:1.147-1047.018, P<0.05). Collateral scores based on CTP and DSA had good consistency (κ=0.697, P<0.01), and ROC curve showed that the predictive value of CTP-CS and DSA-CS were comparable (both AUC=0.726, 95%CI:0.559-0.893, P<0.05). CONCLUSIONS: CTP-CS can predict the clinical outcome of patients with anterior circulation ischemic stroke after thrombectomy.
Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Trombectomia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Angiografia Cerebral , Circulação Colateral , Humanos , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Trombectomia/efeitos adversos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the effect of tirofiban on hemorrhagic transformation and neurological outcome in patients with acute cerebral infarct treated with endovascular therapy. METHODS: One hundred and fifteen patients with acute cerebral infarct who received endovascular stent mechanical thrombectomy in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and April 2017 were included in the study. Among 115 patients, 30 received tirofiban treatment. Hemorrhagic transformation and neurological outcomes were assessed using the ECASS â ¡ criteria and modified Rankin scale (mRS), respectively. Unfavorable outcome was defined as mRS>2. Binary logistic regression model was used to analyze the independent predictors of hemorrhagic transformation and neurological outcome. RESULTS: Binary logistic regression analysis showed that tirofiban treatment did not increase the risk of hemorrhagic transformation (OR=0.437, 95% CI:0.168-1.132, P>0.05); baseline NIHSS (OR=1.136, 95% CI:1.014-1.273, P<0.05), recanalization (OR=0.060, 95% CI:0.010-0.365, P<0.01), hypertension (OR=4.233, 95% CI:1.320-13.570, P<0.05) and onset to treatment time(OR=1.006, 95% CI:1.001-1.011, P<0.05) were independently associated with unfavorable outcome, while such association was not observed in tirofiban treatment (OR=1.923, 95% CI:0.536-6.568, P>0.05). CONCLUSIONS: Tirofiban appears to be safe for patients with acute cerebral infarct receiving endovascular therapy.