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Triply interlocked [2]catenane complexes featuring two identical, mechanically interlocked units are extraordinarily rare chemical compounds, whose properties and applications remain open to detailed studies. Herein, we introduce the rational design of a new ligand precursor, L1, suitable for the synthesis of six triply interlocked [2]catenanes by coordination-driven self-assembly. The interlocked compounds can be reversibly converted into the corresponding simple triangular prism metallacage by addition of H2O or DMF solvents to their CH3OH solutions, thereby demonstrating the importance of πâ â â π stacking and hydrogen bonding interactions in the formation of triply interlocked [2]catenanes. Moreover, extensive studies have been conducted to assess the remarkable photothermal conversion performance. Complex 6 a, exhibiting outstanding photothermal conversion performance (conversion efficiency in solution : 31.82 %), is used to prepare novel photoresponsive elastomer in combination with thermally activated liquid crystal elastomer. The resultant material displays robust response to near-infrared (NIR) laser and the capability of completely reforming the shape and reversible actuation, paving the way for the application of half-sandwich organometallic units in photo-responsive smart materials.
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BACKGROUND: Patients with stroke are often affected by varying degrees of functional disability and have different evolution patterns in functional disability. However, little is known about the predictive usefulness of disability changes after stroke. We aimed to describe 1-year disability trajectories and to assess the associations of longitudinal disability trajectories with 24-month clinical outcomes after ischemic stroke. METHODS AND RESULTS: A total of 3533 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were studied. Distinct trajectories of disability were identified by the group-based trajectory model, as measured by modified Rankin Scale score within 12 months. Cox proportional hazards regression models were used to examine the associations of disability trajectories with 24-month cardiovascular events and all-cause mortality. We identified 4 distinct disability trajectories: no significant disability (562 participants [15.9%]), slight disability to recovery (1575 participants [44.6%]), severe to moderate disability (1087 participants [30.8%]), and persistent severe disability (309 participants [8.7%]). Compared with no significant disability trajectory, the multivariable adjusted hazard ratios (95% CIs) of patients within the persistent heavy-severe trajectory were 2.63 (1.20-5.76) for cardiovascular events, 2.55 (1.12-5.79) for recurrent stroke, and 6.10 (2.22-16.72) for all-cause mortality; notably, the hazard ratios (95% CIs) for patients within the severe to moderate disability trajectory were 1.99 (1.01-3.94) for cardiovascular events and 1.85 (1.03-3.33) for the composite outcome of cardiovascular events and all-cause mortality. CONCLUSIONS: Functional disability trajectories within 12 months after stroke onset were associated with the risk of 24-month adverse outcomes. Patients with persistent severe disability or severe to moderate disability had higher risk of cardiovascular events and all-cause mortality. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Resultado do Tratamento , Infarto CerebralRESUMO
BACKGROUND: Clinically significant changes in neurological deficits frequently occur after stroke onset, reflecting further neurological injury or neurological improvement. However, the National Institutes of Health Stroke Scale (NIHSS) score is only evaluated once in most studies, usually at stroke onset. Utilizing repeated measures of NIHSS scores to identify different trajectories of neurological function may be more informative and provide more useful predictive information. We determined the association of neurological function trajectories with long-term clinical outcomes after ischemic stroke. METHODS: A total of 4025 participants with ischemic stroke from the China Antihypertensive Trial in Acute Ischemic Stroke were included. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. A group-based trajectory model was used to identify distinct neurological function trajectories, as measured by NIHSS at admission, 14 days or hospital discharge, and 3 months. Study outcomes were cardiovascular events, recurrent stroke, and all-cause mortality during 3-24 months after ischemic stroke onset. Cox proportional hazards models were used to examine the associations of neurological function trajectories with outcomes. RESULTS: We identified three distinct subgroups of NIHSS trajectories: persistent severe (persistent high NIHSS scores during the 3-month follow-up), moderate (NIHSS scores started at around 5 and gradually reduced), and mild (NIHSS scores always below 2). The three trajectory groups had different clinical profiles and different risk of stroke outcomes at 24-month follow-up. Compared to the mild trajectory group, patients in the persistent severe trajectory group had a higher risk of cardiovascular events (multivariable-adjusted hazard ratios (95% confidence intervals) = 1.77 (1.10-2.86)), recurrent stroke (1.82 (1.10-3.00)), and all-cause mortality (5.64 (3.37-9.43)). Those with moderate trajectory had an intermediate risk: 1.45 (1.03-2.04) for cardiovascular events and 1.52 (1.06-2.19) for recurrent stroke. CONCLUSION: Longitudinal neurological function trajectories derived from repeated NIHSS measurements during the first 3 months after stroke provide additional predictive information and are associated with long-term clinical outcomes. The trajectories characterized by persistent severe and moderate neurological impairment were associated with increased risk of subsequent cardiovascular events.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Infarto Cerebral/complicações , China/epidemiologia , AVC Isquêmico/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND AND AIMS: l-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study. METHODS AND RESULTS: A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57-0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58-0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21-0.57) and 0.36 (95% CI: 0.21-0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement. CONCLUSIONS: Higher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke. TRIAL REGISTRATION: Clinicaltrials.gov as NCT01840072. URL: https://www. CLINICALTRIALS: gov.
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Carnitina , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores , Carnitina/efeitos adversos , Estudos de Casos e Controles , Cromatografia Líquida , Eletrólitos , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , AVC Isquêmico/prevenção & controle , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Espectrometria de Massas em TandemRESUMO
BACKGROUND AND PURPOSE: Neuropeptide Y (NPY) has a modulatory role in learning and memory, and is involved in the pathophysiology of neurodegenerative diseases. However, there was no population-based evidence on the relationship between NPY and post-stroke cognitive impairment (PSCI). We aimed to prospectively examine the association between plasma NPY and cognitive impairment among patients with acute ischemic stroke. METHODS: On the basis of samples from the China Antihypertensive Trial in Acute Ischemic Stroke, 593 patients with baseline plasma NPY levels were finally included in this study. The study outcome was cognitive impairment (Montreal Cognitive Assessment score < 26) at 3 months after ischemic stroke. Logistic regression models were used to estimate the risk of cognitive impairment. RESULTS: After 3 months of follow-up, 422 participants (71.2 %) experienced cognitive impairment. Multivariable-adjusted odds ratio (95 % confidence interval) for the highest tertile of NPY was 0.58 (0.36-0.92) compared with the lowest tertile. Each 1-SD higher log-NPY was associated with a decreased risk of 20 % (95 % confidence interval 2 %-34 %) for PSCI. The addition of plasma NPY to the basic model with conventional risk factors improved the risk reclassification (continuous net reclassification index was 22.8 %, p = 0.01; integrated discrimination improvement was 0.9 %, p = 0.02) for PSCI. LIMITATIONS: We measured plasma NPY only once at baseline and failed to explore the association between NPY changes and PSCI. CONCLUSIONS: Elevated plasma NPY levels were associated with a decreased risk of cognitive impairment, suggesting plasma NPY may serve as a predictive factor and potential therapeutic target for PSCI.
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Isquemia Encefálica , Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Anti-Hipertensivos , Ensaios Clínicos como Assunto , Humanos , Neuropeptídeo Y , Acidente Vascular Cerebral/psicologiaRESUMO
BACKGROUND: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which reflects microglia activation, has been reported closely associated with neuronal injury and neuroinflammation. We aimed to prospectively investigate the associations between plasma sTREM2 and clinical outcomes in acute ischemic stroke (AIS) patients. METHODS: Study participants were from the China Antihypertensive Trial in Acute Ischemic Stroke, plasma sTREM2 levels in the acute phase of AIS were measured in 3285 participants. The study outcomes were death, cardiovascular events and severe disability at 1 year after AIS. Cox proportional hazards models or logistic regression models were performed to examine the associations of plasma sTREM2 and clinical outcomes. RESULTS: After 1-year follow-up, 288 participants (8.8%) experienced cardiovascular events or died. Multivariable-adjusted hazard ratios or odds ratios (95% confidence intervals) for the highest quartile of sTREM2 were 1.57 (1.11-2.21) for the composite outcome of death and cardiovascular events, 1.68 (1.09-2.60) for death, and 1.53 (1.08-2.18) for death or severe disability compared to the lowest quartile. Moreover, incorporation sTREM2 into traditional risk factors model significantly improved risk prediction of the composite outcome of death and cardiovascular events as evidenced by net reclassification index and integrated discrimination improvement (all p values < 0.05). There were joint effects of sTREM2 and galectin-3 on death and cardiovascular events. Participants with simultaneous elevation of sTREM2 and galectin-3 levels had the highest risk of the composite outcome of death and cardiovascular events. CONCLUSIONS: Elevated sTREM2 levels were independently associated with increased risks of death and cardiovascular events after AIS.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Galectina 3 , Humanos , Glicoproteínas de Membrana , Células Mieloides , Receptores ImunológicosRESUMO
BACKGROUND: L-carnitine has been shown to exert neuroprotective effects on cerebral ischemia, mainly by improving mitochondrial function and reducing inflammation. L-carnitine supplementation has also been promoted to enhance cognitive function. However, the relationship between L-carnitine and cognitive impairment after ischemic stroke has seldom been studied. OBJECTIVE: We aimed to evaluate the association between plasma L-carnitine and poststroke cognitive impairment. METHODS: The study sample population was drawn from the China Antihypertensive Trial in Acute Ischemic Stroke. Plasma L-carnitine were measured at baseline in 617 patients with ischemic stroke using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3-month follow-up after ischemic stroke. RESULTS: Plasma L-carnitine were inversely associated with cognitive impairment at 3 months after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartiles of L-carnitine was 0.60 (0.37, 0.98; p for trendâ=â0.04). Each 1-SD increase in log-transformed L-carnitine concentration was significantly associated with a 15% (95% CI: 1%, 29%) reduction in the risk of cognitive impairment after stroke. The addition of L-carnitine to the model including conventional risk factors significantly improved the risk reclassification for cognitive impairment (net reclassification improvement: 17.9%, integrated discrimination improvement: 0.8%; both pâ<â0.05). Furthermore, joint effects of L-carnitine and inflammation markers were observed, and patients with higher L-carnitine and a lower inflammatory status simultaneously had the lowest risk of poststroke cognitive impairment. CONCLUSION: The present study provided prospective evidence on the inverse association between plasma L-carnitine and cognitive impairment after ischemic stroke.
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Isquemia Encefálica , Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Carnitina , Disfunção Cognitiva/epidemiologia , Humanos , Inflamação/complicações , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: Previous researches have suggested that soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays a pivotal role in central nervous system pathologies and the development of neurodegenerative disorders. This study aimed to prospectively investigate the association between plasma sTREM2 levels and post-stroke cognitive impairment (PSCI). METHODS: A sample of 599 consecutive acute ischemic stroke patients with sTREM2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were eventually included in this analysis. Cognitive impairment was defined as a score of <25 for Mini-Mental State Examination, measured at 3-month follow up. Binary logistic regression was used to estimate the odds ratios (ORs) of plasma sTREM2 levels on the risk of PSCI. RESULTS: Of the 599 participants (mean age, 60.0 ± 10.4 years; male, 70.5%), 228 (38.1%) patients were diagnosed as PSCI. The risk of PSCI elevated significantly with higher plasma sTREM2 levels (p for trend <0.01). After adjusting for several confounding factors, the ORs for the highest quartile of sTREM2 compared with the lowest quartile was 2.06 (95% confidence interval, 1.20-3.53) for PSCI. Moreover, the addition of sTREM2 to the conventional model with established risk factors significantly improved risk discrimination (C-statistics increased from 0.668 to 0.691, p = 0.02) and reclassification (net reclassification improvement: 32.2%, p < 0.001; integrated discrimination improvement: 1.3%, p = 0.01) for PSCI. LIMITATIONS: Results might be subject to selective bias and potential confounding. CONCLUSIONS: The present study demonstrated that elevated level of plasma sTREM2 may be associated with PSCI, and sTREM2 has potential value in predicting PSCI.
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Isquemia Encefálica , Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/complicações , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células Mieloides , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Choline pathway nutrients, including choline and betaine, are reported to exert antidepressant effects. However, there is little population-based evidence on the relationships between circulating choline and betaine and poststroke depression (PSD). We aimed to prospectively explore the associations between plasma choline and betaine and depression after ischemic stroke. METHODS: This study was based on the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 612 participants with plasma choline and betaine concentrations were included in the analysis. The study outcome was depression 3 months after ischemic stroke. Logistic regression models were performed to estimate the relationships between plasma choline and betaine and the risk of PSD. Risk reclassification and calibration of models with choline or betaine were analyzed. RESULTS: Patients with PSD had lower choline and betaine levels than those without PSD (p < 0.05). Compared with tertile 1, the multivariable-adjusted odds ratios (95% CIs) for tertile 3 of choline and betaine were 0.54 (0.35-0.83) and 0.59 (0.38-0.92), respectively. Per 1 SD increase in choline or betaine was associated with a 25% (95% CI 9%-37%) or an 19% (95% CI 3%-32%) decreased risk of PSD, respectively. Furthermore, the addition of choline or betaine to the established risk factors model improved the risk reclassification for PSD, as shown by an increase in the net reclassification index and integrated discrimination improvement (all p < 0.05). CONCLUSIONS: Patients with elevated levels of choline and betaine had a lower risk of depression after acute ischemic stroke, suggesting the protective significance of choline pathway nutrients for PSD.
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AVC Isquêmico , Acidente Vascular Cerebral , Colina , Depressão/etiologia , Humanos , Nutrientes , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: The association between annual household income and prognosis of ischaemic stroke remains debatable. We aimed to prospectively investigate the relationship between annual household income and prognosis at 3 months after ischaemic stroke. METHODS: We included 3975 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. All participants were categorised into three groups according to annual household income per capita: <¥10 000 (Chinese Yuan Renminbi (RMB)), ¥10 000-19 999 and ≥¥20 000. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset, and secondary outcomes included major disability, death, and vascular events. A meta-analysis was conducted to incorporate the results of the current study and previous studies on the association of income level with outcomes after stroke. RESULTS: Within 3 months after ischaemic stroke, 1002 participants (25.20%) experienced primary outcome (880 major disabilities and 122 deaths). After multivariate adjustment, low annual household income level was associated with increased risk of the primary outcome (OR 1.60; 95% CI: 1.12 to 2.31; Ptrend=0.034) when two extreme groups were compared. The meta-analysis confirmed the significant association between income level and death or major disability after stroke (pooled relative risk for lowest vs highest income level, 1.31 (95% CI: 1.18 to 1.45)). CONCLUSIONS: Low annual household income per capita was significantly associated with increased risks of adverse clinical outcomes at 3 months after ischaemic stroke, independently of established risk factors. Further studies from other samples are needed to replicate our findings due to a reason for excluding some patients who had a severe stroke in this study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (http://wwwclinicaltrialsgov) Registry (NCT01840072).
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Anti-Hipertensivos/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Humanos , Prognóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND AND AIMS: Osteopontin is implicated in atherosclerosis, and its expression is upregulated in response to brain injury. The aim of this study was to prospectively investigate the associations between plasma osteopontin levels and adverse clinical outcomes in ischemic stroke patients. METHODS: We measured baseline plasma osteopontin levels in 3545 ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was the composite outcome of death and major disability (modified Rankin scale score ≥3) at 1 year after ischemic stroke, and secondary outcomes included major disability, death, and the composite outcome of death and vascular events. RESULTS: During 1 year of follow-up, patients in the fourth quartile of plasma osteopontin had the highest risks of primary outcome, major disability, death, and the composite outcome of death and vascular events. After multivariate adjustment, the odds ratios or hazard ratios (95 % confidence intervals) associated with each standard deviation increase in log-transformed osteopontin were 1.20 (1.09-1.33) for primary outcome, 1.11 (1.00-1.23) for major disability, 1.29 (1.10-1.52) for death, and 1.15 (1.01-1.30) for the composite outcome of death and vascular events. The addition of plasma osteopontin to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement: 16.91%, p < 0.001; integrated discrimination improvement: 0.43%, p = 0.002). CONCLUSIONS: Elevated plasma osteopontin levels at baseline were associated with increased risks of adverse clinical outcomes at 1 year after ischemic stroke, suggesting that osteopontin is a promising prognostic biomarker for ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Isquemia Encefálica/diagnóstico , Humanos , Osteopontina , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/diagnósticoRESUMO
BACKGROUND: Choline and betaine have been suggested to play a pivotal role in neurotransmitter synthesis, cell membrane integrity, and methyl-group metabolism, exerting neuroprotective effects in patients with various neurological disorders. However, population-based evidence on choline and betaine with subsequent cardiovascular events after stroke is rare. OBJECTIVES: We aimed to prospectively investigate the relationships of circulating choline and betaine with cardiovascular events and recurrent stroke in patients with ischemic stroke. METHODS: We performed a nested case-control study within the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 controls (free of recurrent cardiovascular events) matched for age (±1 y), sex, and treatment group were included. The primary endpoint was a composite of cardiovascular events after ischemic stroke. Plasma choline and betaine were measured at baseline by ultra-high-performance LC-MS/MS. Conditional logistic regression models were applied, and discrimination, reclassification, and calibration of models with choline pathway metabolites were evaluated. RESULTS: Plasma choline and betaine were inversely associated with cardiovascular events and recurrent stroke after ischemic stroke. Specifically, in fully adjusted models, each additional SD of choline and betaine was associated with 35% (95% CI: 20%-48%) and 30% (95% CI: 14%-43%) decreased risks of subsequent cardiovascular events, respectively, and 34% (95% CI: 16%-48%) and 29% (95% CI: 12%-43%) decreased risks of recurrent stroke, respectively. In addition, both choline and betaine offered substantial risk discrimination and reclassification improvement for cardiovascular events and recurrent stroke beyond traditional risk factors, as evidenced by an increase in C statistics, the net reclassification index, and integrated discrimination improvement. CONCLUSIONS: Plasma choline pathway metabolites, including choline and betaine, were associated with decreased risks of cardiovascular events and recurrent stroke and provided incremental value in risk discrimination and stratification in patients with ischemic stroke. This nested case-control study was based on the China Antihypertensive Trial in Acute Ischemic Stroke, which is registered at clinicaltrials.gov as NCT01840072.
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Betaína/sangue , Doenças Cardiovasculares/prevenção & controle , Colina/sangue , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Lipotrópicos/sangue , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/sangue , RecidivaRESUMO
BACKGROUND: Soluble suppression of tumorigenesis-2 (sST2) was reported to be associated with cognitive performance and risk of incident stroke. However, the impact of sST2 on cognitive function after ischemic stroke is unclear. We aimed to assess the association of sST2 and cognitive impairment at 3 months in acute ischemic stroke patients. METHODS: Baseline plasma sST2 levels were measured in 619 ischemic stroke patients (mean age: 60.0 ± 10.5 years) from 7 participating hospitals of the China Antihypertensive Trial in Acute Ischemic Stroke. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status. Cognitive impairment was defined as a MoCA score < 23 or MMSE score < 27. The association between sST2 and cognitive impairment was evaluated by logistic regression analysis. RESULTS: 325 (52.5%) or 323 (52.2%) participants developed cognitive impairment according to MoCA or MMSE. After adjustment for age, sex, education, and other covariates, the odds ratio for the highest vs lowest quartile of sST2 was 2.38 (95% CI, 1.42-4.00) and 1.82 (95% CI 1.09-3.03) risk of cognitive impairment defined by MoCA and MMSE score, respectively. Incorporation sST2 into a model containing conventional risk factors significantly improved reclassification. CONCLUSIONS: Elevated plasma sST2 levels were significantly associated with post-stroke cognitive impairment.
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Isquemia Encefálica , Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Testes Neuropsicológicos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.
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[Figure: see text].
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Pressão Sanguínea/fisiologia , Encéfalo/fisiopatologia , Hipertensão/fisiopatologia , AVC Isquêmico/fisiopatologia , Modelos Cardiovasculares , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de TempoRESUMO
AIMS: Angiopoietin-like protein 4 (ANGPTL-4) had been reported to be associated with the risk of ischemic stroke, but its prognostic value remained unclear. The aim of this study was to investigate the association between plasma ANGPTL-4 concentrations and prognosis of ischemic stroke. METHODS: Baseline plasma ANGPTL-4 concentrations were measured in 3379 acute ischemic stroke patients. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after ischemic stroke. RESULTS: At 3 months after ischemic stroke, 850 (26.16%) participants experienced major disability or died (750 major disabilities and 100 deaths). After adjusting for important covariates, odds ratios for the highest tertile of plasma ANGPTL-4 concentrations were 1.59 (1.22-2.06) for primary outcome, 1.53 (1.18-1.97) for major disability, and 2.03 (1.03-4.00) for death when compared with the lowest tertile of plasma ANGPTL-4 concentrations. For 1-SD increase in log-ANGPTL-4 concentrations (0.44 ng/mL), the adjusted odds ratios were 1.24 (1.11-1.38), 1.14 (1.03-1.27), and 1.72 (1.32-2.23), respectively. Adding ANGPTL-4 to a model containing conventional risk factors improved risk prediction for composite outcome of death and major disability. CONCLUSION: Higher plasma ANGPTL-4 concentration was associated with poor prognosis in acute ischemic stroke patients, suggesting that ANGPTL-4 might be a prognostic marker for ischemic stroke.
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Proteína 4 Semelhante a Angiopoietina/sangue , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Doença Aguda , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , AVC Isquêmico/mortalidade , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND AND PURPOSE: Choline metabolism was suggested to play pathophysiological roles in nervous system and atherosclerosis development. However, little is known about the impacts of choline pathway nutrients and metabolites on poststroke cognitive impairment. We aimed to prospectively investigate the relationships between circulating choline, betaine, and trimethylamine N-oxide with cognitive impairment among acute ischemic stroke patients. METHODS: We derived data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Plasma choline, betaine, and trimethylamine N-oxide concentrations at baseline were measured in 617 participants. Cognitive impairment was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Reclassification and calibration of models with choline-related biomarkers were evaluated. RESULTS: Plasma choline and betaine were inversely associated with cognitive impairment. Compared with the lowest tertile, adjusted odds ratios of Mini-Mental State Examination-defined cognitive impairment for participants in the highest tertiles of choline and betaine were 0.59 (95% CI, 0.39-0.90) and 0.60 (95% CI, 0.39-0.92), respectively. In addition, both choline and betaine offered incremental predictive ability over the basic model with established risk factors, shown by increase in net reclassification improvement and integrated discrimination improvement. There were similar significant relationships between choline and betaine with cognitive impairment as defined by the Montreal Cognitive Assessment. However, plasma trimethylamine N-oxide was only associated with cognitive impairment evaluated using the Mini-Mental State Examination; the adjusted odds ratio was 1.33 (95% CI, 1.04-1.72) for each 1-SD increment of trimethylamine N-oxide. CONCLUSIONS: Patients with higher choline and betaine levels had lower risk of cognitive impairment after ischemic stroke, supporting promising prognostic roles of choline pathway nutrients for poststroke cognitive impairment.
Assuntos
Colina/metabolismo , Transtornos Cognitivos/metabolismo , AVC Isquêmico/terapia , Idoso , Anti-Hipertensivos/farmacologia , Isquemia Encefálica/diagnóstico , China , Colina/química , Cognição , Disfunção Cognitiva/etiologia , Feminino , Humanos , Hipertensão/terapia , Masculino , Metilaminas/metabolismo , Pessoa de Meia-Idade , Prognóstico , Método Simples-Cego , Acidente Vascular Cerebral/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: To evaluate the association between plasma fibroblast growth factor 21 (FGF-21) and clinical outcomes in patients with acute ischemic stroke. METHODS: A total of 3412 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke with plasma FGF-21 measurements were included in this analysis. The primary outcome was a combination of death or major disability (modified Rankin Scale score ≥3) within 1 year after stroke. RESULTS: During the 1-year of follow-up, 745 (21.83%) patients experienced the primary outcome; 550 had a major disability and 195 died. After multivariate adjustment, higher plasma FGF-21 was significantly associated with increased risk of the primary outcome (odds ratio = 1.52, 95% confidence interval = 1.11-1.29). Each 1-SD increase of log-transformed FGF-21 (0.67 pg/ml) was associated with 19%, 3%, and 33% increased risk of the primary outcome, major disability, and death, respectively. The addition of FGF-21 to the conventional risk factors significantly improved prediction of the primary outcome in ischemic stroke patients (net reclassification index = 10.8%, p = 0.011; integrated discrimination improvement = 0.3%, p = 0.038). CONCLUSIONS: Higher plasma FGF-21 was associated with poor prognosis in acute ischemic stroke patients, suggesting that FGF-21 may be a prognostic marker for ischemic stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Isquemia Encefálica/complicações , Fatores de Crescimento de Fibroblastos , Humanos , PrognósticoRESUMO
BACKGROUND: To assess the potential incremental utility of multiple biomarkers reflecting several pathological pathways for the risk prediction of depression after stroke. METHODS: We used data from the China Antihypertensive Trial in Acute Ischemic Stroke, and a panel of 13 circulating biomarkers were measured. The study outcome was depression (24-item Hamilton Depression Rating Scale score≥8) at 3 months after ischemic stroke. Logistic regression models were performed to evaluate the risk of depression associated with multiple biomarkers. Discrimination and risk reclassification for depression were analyzed. RESULTS: Among 631 included ischemic stroke patients, elevated growth differentiation factor-15, anticardiolipin antibodies, antiphosphatidylserine antibodies and matrix metalloproteinase-9 were individually associated with increased risks of depression after stroke. The multiple biomarker analysis showed a clear gradient in the risk of depression with increasing numbers of elevated biomarkers, and multivariate adjusted odds ratio (95% confidence interval) of patients with 4 elevated biomarkers was 6.52 (2.24-18.95) compared with those without elevation in any of 4 biomarkers. The simultaneous inclusion of all 4 biomarkers to the conventional model significantly improved discrimination (C statistic increased from 0.702 to 0.748, P=0.004) and risk reclassification (net reclassification improvement 45.0%; integrated discrimination improvement 6.2%; both P<0.001) for depression after stroke. LIMITATIONS: We selected biomarkers that had previously been reported to be promising predictors of depression after stroke, while other novel biomarkers not tested might have additional predictive value. CONCLUSIONS: Simultaneously adding multiple biomarkers from several pathophysiological pathways to traditional risk factors provided substantial incremental utility of the risk stratification for depression after stroke.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Isquemia Encefálica/complicações , China , Depressão/diagnóstico , Depressão/etiologia , Humanos , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD. METHODS: A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2. RESULTS: Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10-3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category-free NRI = 19.34%, 95% confidence interval = 4.39%-34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%-2.15%, p = 0.014). CONCLUSIONS: Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors.