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1.
Eur J Neurol ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33960072

RESUMO

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

2.
Cerebrovasc Dis ; 50(3): 245-261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33756459

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , COVID-19/complicações , Heparina de Baixo Peso Molecular/farmacologia , SARS-CoV-2/patogenicidade , Acidente Vascular Cerebral/etiologia , COVID-19/virologia , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Acidente Vascular Cerebral/diagnóstico
3.
PLoS One ; 16(2): e0246684, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33577590

RESUMO

BACKGROUND: To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT). METHODS: We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups. RESULTS: The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29-16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09). CONCLUSIONS: HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years.

4.
BMC Neurol ; 21(1): 30, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468088

RESUMO

BACKGROUND: Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. METHODS: Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. RESULTS: 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. CONCLUSIONS: Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.


Assuntos
Estenose das Carótidas/etiologia , Irradiação Craniana/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Hipotireoidismo/etiologia , Lesões por Radiação/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/epidemiologia , Feminino , Humanos , Hipotireoidismo/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
5.
Cell Commun Signal ; 18(1): 185, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228717

RESUMO

BACKGROUND: The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear. METHODS: Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway. RESULTS: Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration. CONCLUSION: These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes. Video Abstract.

6.
PLoS One ; 15(11): e0241891, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211729

RESUMO

BACKGROUND: Stroke is prevalent in patients with chronic kidney disease (CKD) and is associated with high mortality, but the causes of death after stroke among different CKD stages are not well known. AIMS: We aimed to investigate whether the severity of CKD would impact on the causes of death after first-ever stroke. METHODS: This retrospective multicenter cohort study included stoke patients with CKD between 2007 and 2012. The cause of death and date of death were ascertained by linking the National Death Registry Database of Taiwan. Clinical outcomes, 1-month, and 1-year mortality rates, and major causes of death were compared according to five CKD stages (G1 to G5) in the ischemic and hemorrhagic stroke separately. RESULTS: Of these patients, 9,878 were first-ever ischemic stroke (IS) patients, and 1,387 were first-ever hemorrhagic stroke (HS) patients. Patients with CKD G5 had the highest one-year mortality rate with hazard ratio 5.28 [95%CI, 3.94-7.08] in IS and 3.03 [95%CI, 2.03-4.54] in HS when compared to G1 patients. Leading causes of one-year death after IS were stroke, cancer, and pneumonia in early (G1-3) CKD patients, while diabetes mellitus, CKD, and stroke itself contributed to the major mortality in CKD G5 patients. An inverse association between eGFR decrement and the proportion of deaths caused by stroke itself was observed in CKD G2-5 patients after IS. Stroke was the leading cause of one-year death among all CKD patients after HS. CONCLUSIONS: Asides from high mortality, late-stage CKD patients had different causes of death from early CKD patients after stroke. This study highlights the need to imply different treatment strategies in late-stage CKD post-stroke patients to improve their prognosis.

7.
J Neuroinflammation ; 17(1): 308, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069238

RESUMO

BACKGROUND: The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke. METHODS: We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < - 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables. RESULTS: Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke. CONCLUSION: The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

8.
J Hypertens ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031175

RESUMO

OBJECTIVE: Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study. METHODS: Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (>150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (<180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (>10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0-15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09-2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43-0.92; P = 0.016). CONCLUSION: Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01422616.

9.
J Neurol Sci ; 419: 117187, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33075592

RESUMO

OBJECTIVE: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care. METHOD: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders. RESULTS: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12-0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy). CONCLUSION: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).

10.
J Neuroeng Rehabil ; 17(1): 131, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993692

RESUMO

BACKGROUND: Accurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models. METHODS: This study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models. RESULTS: Three important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77. CONCLUSIONS: Incorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.

11.
Int J Mol Sci ; 21(17)2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32872405

RESUMO

Oxidative stress is a key contributor to the pathogenesis of stroke-reperfusion injury. Neuroinflammatory peptides released after ischemic stroke mediate reperfusion injury. Previous studies, including ours, have shown that lipocalin-2 (LCN2) is secreted in response to cerebral ischemia to promote reperfusion injury. Genetic deletion of LCN2 significantly reduces brain injury after stroke, suggesting that LCN2 is a mediator of reperfusion injury and a potential therapeutic target. Immunotherapy has the potential to harness neuroinflammatory responses and provides neuroprotection against stroke. Here we report that LCN2 was induced on the inner surface of cerebral endothelial cells, neutrophils, and astrocytes that gatekeep the blood-brain barrier (BBB) after stroke. LCN2 monoclonal antibody (mAb) specifically targeted LCN2 in vitro and in vivo, attenuating the induction of LCN2 and pro-inflammatory mediators (iNOS, IL-6, CCL2, and CCL9) after stroke. Administration of LCN2 mAb at 4 h after stroke significantly reduced neurological deficits, cerebral infarction, edema, BBB leakage, and infiltration of neutrophils. The binding epitope of LCN2 mAb was mapped to the ß3 and ß4 strands, which are responsible for maintaining the integrity of LCN2 cup-shaped structure. These data indicate that LCN2 can be pharmacologically targeted using a specific mAb to reduce reperfusion injury after stroke.

12.
J Neurointerv Surg ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883782

RESUMO

BACKGROUND: Endovascular thrombectomy (ET) has transformed acute ischemic stroke (AIS) therapy in patients with large vessel occlusion (LVO). Left ventricular systolic dysfunction (LVSD) decreases global cerebral blood flow and predisposes to hypoperfusion. We evaluated the relationship between LVSD, as measured by LV ejection fraction (LVEF), and clinical outcomes in patients with anterior cerebral circulation LVO who underwent ET. METHODS: This multicenter retrospective cohort study examined anterior circulation LVO AIS patients from six international stroke centers. LVSD was measured by assessment of the echocardiographic LVEF using Simpson's biplane method of discs according to international guidelines. LVSD was defined as LVEF <50%. The primary outcome was defined as a good functional outcome using a modified Rankin Scale (mRS) of 0-2 at 3 months. RESULTS: We included 440 AIS patients with LVO who underwent ET. On multivariate analyses, pre-existing diabetes mellitus (OR 2.05, 95% CI 1.24 to 3.39;p=0.005), unsuccessful reperfusion (Treatment in Cerebral Infarction (TICI) grade 0-2a) status (OR 4.21, 95% CI 2.04 to 8.66; p<0.001) and LVSD (OR 2.08, 95% CI 1.18 to 3.68; p=0.011) were independent predictors of poor functional outcomes at 3 months. On ordinal (shift) analyses, LVSD was associated with an unfavorable shift in the mRS outcomes (OR 2.32, 95% CI 1.52 to 3.53; p<0.001) after adjusting for age and ischemic heart disease. CONCLUSION: Anterior circulation LVO AIS patients with LVSD have poorer outcomes after ET, suggesting the need to consider cardiac factors for ET, the degree of monitoring and prognostication post-procedure.

13.
J Hypertens ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32897905

RESUMO

OBJECTIVE: As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke. METHODS: Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015-2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3-6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120-139 and 70-89 mmHg, respectively). RESULTS: Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear 'J-shaped' relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02-1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke. CONCLUSION: The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.

14.
Ther Adv Chronic Dis ; 11: 2040622320936418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32843953

RESUMO

Background: Previous clinical trials showed a significant difference in efficacy and safety among antiplatelets in acute ischemic stroke (IS). The present study wished to compare the efficacy and safety head-to-head between cilostazol and clopidogrel in chronic IS. Methods: This open prospective cohort study recruited chronic IS patients with an index hospitalization between 2001 and 2013 from Taiwan National Health Insurance Research Database. In the 504,191 hospitalized patients, patients who had missing information and history of atrial fibrillation or rheumatic heart disease, received mechanical valve replacement or anticoagulants, expired during the index hospitalization, received follow-up ⩽6 months, or had recurrent stroke within 6 months after index stroke were excluded. Results: Among the 15,968 eligible patients, 502 patients who consistently received either cilostazol or clopidogrel from the 7th month after the index stroke were included for analysis after propensity score matching. The 3-year primary outcomes showed similar frequency of recurrent IS, all-cause mortality, and acute myocardial infarction (AMI), and similar frequency of intracerebral hemorrhage, gastrointestinal bleeding, and major bleeding between the cilostazol and clopidogrel groups. Subgroup analysis revealed that patients with a history of hypertension or gastrointestinal bleeding had a trend of having lower frequency of recurrent IS or major bleeding, respectively, in the cilostazol group. Conclusion: The present real-world study demonstrated no significant difference in efficacy and safety between cilostazol and clopidogrel in chronic IS. However, cilostazol might be better than clopidogrel in patients with a history of hypertension or gastrointestinal bleeding.

15.
Int J Stroke ; : 1747493020938297, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640882

RESUMO

BACKGROUND: Enhancing detection of unrecognized atrial fibrillation among acute ischemic stroke patients is crucial for secondary stroke prevention. AIM: To evaluate whether the detection rate of new atrial fibrillation in acute ischemic stroke patients without known atrial fibrillation could be improved by doing serial 12-lead electrocardiograms once daily for five days, compared with conventional 24-h Holter monitoring (24-h Holter). METHODS: We conducted a randomized clinical trial to compare the detection rates of paroxysmal atrial fibrillation between serial electrocardiograms versus 24-h Holter from October 2015 to October 2018 at six hospitals. Eligible participants were acute ischemic stroke patients with aged ≥65 years, with neither atrial fibrillation history nor any presence of atrial fibrillation on baseline electrocardiogram at admission. The primary outcome was newly detected electrocardiogram in the serial electrocardiograms and 24-h Holter group. RESULTS: Among 826 patients, baseline characteristics were similar between both groups. In the intention-to-treat analysis, there was no statistical difference between serial electrocardiograms versus 24-Holter to detect atrial fibrillation (8.4% vs. 6.9%; adjusted odds ratio 1.17, 95% confidence interval 0.69-2.01). Stepwise multivariate logistic regression revealed age ≥80 years and history of heart failure were associated with detection of paroxysmal atrial fibrillation whereas patients with lacunar infarction had lower odds for detection of paroxysmal atrial fibrillation. CONCLUSIONS: Serial electrocardiograms had comparable detection rate of paroxysmal atrial fibrillation compared with 24-h Holter and might be a viable alternative to 24-h Holter as a first-line approach to survey for potential paroxysmal atrial fibrillation among elderly patients with acute ischemic stroke.Clinical Trial Registration: URL https://clinicaltrials.gov/ct2/show/NCT02578979Unique Identifiers: NCT02578979.

16.
Int J Stroke ; : 1747493020938307, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32638639

RESUMO

BACKGROUND AND PURPOSE: To examine sex differences in disease profiles and short-term outcomes after acute ischemic stroke treated with recombinant tissue plasminogen activator. METHODS: Eight national and regional stroke registries contributed individual participant data from mainland China, Japan, Philippines, Singapore, South Korea and Taiwan in 2005-2018. The primary outcome was ordinal-modified Rankin scale at 90 days. Key safety outcome was symptomatic intracerebral hemorrhage (sICH). RESULTS: Of 4453 patients included in the analyses, 1692 (36.3%) were women who were older, more likely to have a more severe neurological deficit, history of hypertension and atrial fibrillation, and a cardioembolic stroke compared to men. Women were more likely than men to have unfavorable shift of modified Rankin scale (fully adjusted odds ratio) (women vs. men) 1.14, 95% confidence interval 1.02-1.28). There was no significant sex difference for death 1.05 (0.84-1.31) or sICH (1.17, 0.89-1.54). Women were more likely to have unfavorable functional outcome with increasing age (P = 0.022 for interaction). In the age groups 70-80 and ≥80 years, women had a worse functional outcome compared to men (1.22, 1.02-1.47 and 1.43, and 1.06-1.92, respectively). CONCLUSION: In this pooled data from Asian acute stroke registries, women had poorer prognosis than men after receiving recombinant tissue plasminogen activator for acute ischemic stroke, which worsened with age. Women older than 70 appear to have a worse outcome than men which could be explained by greater stroke severity, more AF, and cardioembolic stroke.

17.
Sci Rep ; 10(1): 10030, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572272

RESUMO

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-ß1, and ß3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-ß1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-ß1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and ß3-adrenoceptor expression.

18.
Stroke Vasc Neurol ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32591406

RESUMO

BACKGROUND: Although the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP; vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity. METHODS: Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP <4.5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale (mRS) and death/disability (mRS scores 3-6), and any cardiovascular serious adverse event. Logistic regression analyses were undertaken adjusted for study design and baseline risk factors. RESULTS: There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3-6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04); NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19); NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14). CONCLUSIONS: Early FP had no significant effect in patients with moderate-severe AIS. TRIAL REGISTRATION NUMBER: NCT02162017.

19.
J Neuroinflammation ; 17(1): 177, 2020 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-32505192

RESUMO

BACKGROUND: Upregulation of matrix metalloproteinase-9 (MMP-9) has been indicated as one of the inflammatory biomarkers. In the central nervous system (CNS), the MMP-9 is induced by several proinflammatory mediators and participates in the CNS disorders, including inflammation and neurodegeneration. In addition, protein kinase Cs (PKCs) has been shown to be involved in regulation of various inflammatory factors like MMP-9 by several stimuli in many cell types. Several phytochemicals are believed to reduce the risk of several inflammatory disorders including the CNS diseases. The rottlerin, a principal phenolic compound of the Kamala plant Mallotus philippinensis, has been shown to possess an array of medicinal properties, including anti-PKC-δ, antitumor, anti-oxidative, and anti-inflammatory activities. METHODS: Herein, we used rat brain astrocytes (RBA) to demonstrate the signaling mechanisms of phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression by zymographic, RT-PCR, subcellular isolation, Western blot, ROS detection, and promoter reporter analyses. Then, we evaluate the effects of rottlerin on PMA-induced MMP-9 expression in RBA and its influencing mechanism. RESULTS: We first demonstrated that PMA stimulated activation of various types of PKC, including PKC-δ in RBA. Subsequently, PMA induced MMP-9 expression via PKCδ-mediated reactive oxygen species (ROS) generation, extracellular signal-regulated kinase 1/2 (ERK1/2) activation, and then induced c-Fos/AP-1 signaling pathway. Finally, upregulation of MMP-9 by PMA via the pathway may promote astrocytic migration, and the event could be attenuated by rottlerin. CONCLUSIONS: These data indicated that rottlerin may have anti-inflammatory activity by reducing these related pathways of PKC-δ-dependent ROS-mediated MMP-9 expression in brain astrocytes.

20.
Cell Transplant ; 29: 963689720909387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32452747

RESUMO

The effects of human amniotic fluid stem cells (hAFSCs) transplantation on bladder dysfunction after pelvic nerve transection (PNT) remain to be clarified. Five groups of female Sprague-Dawley rats were studied including sham operation, unilateral PNT alone or plus hAFSCs transplantation, and bilateral PNT alone or plus hAFSCs transplantation. hAFSCs were injected at the site of PNT. Cystometries, neurofilament density within bladder nerves, and the expressions of bladder protein gene-product 9.5 (PGP9.5), growth-associated protein 43 (GAP-43), nerve growth factor (NGF), p75 (NGF receptor), CXCL12, CCL7, and enkephalin were studied. Compared to sham-operation group, bladder weight increased and neurofilament density decreased at 10 and 28 days after unilateral and bilateral PNT, but all improved after hAFSCs transplantation. Unilateral PNT could increase bladder capacity, residual volume, and number of nonvoiding contractions but decrease peak voiding pressure and leak point pressure. Bilateral PNT caused overflow incontinence and increased the number of nonvoiding contractions. These cystometric parameters improved after hAFSCs transplantation. After PNT, bladder PGP9.5 mRNA and immunoreactivities decreased at 10 and 28 days, GAP-43 mRNA and immunoreactivities increased at 10 days and decreased at 28 days, both NGF and p75 mRNAs and immunoreactivities increased at 10 and/or 28 days, and enkephalin immunoreactivities decreased at 10 and 28 days, but these were all improved after hAFSCs transplantation. Our results showed that bladder dysfunction induced by PNT could be improved by hAFSCs transplantation, and PGP9.5, GAP-43, and neurotrophins could be involved in the mechanisms of nerve regeneration after hAFSCs transplantation.

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