A performance guide for major risk factors control in patients with atherosclerotic cardiovascular disease in Taiwan.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

Statins and the risk of bleeding in patients taking dabigatran.

OBJECTIVES: Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS: We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS: In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P < 0.001) than non-users. Kaplan-Meier analysis indicated that patients prescribed with statins had a higher rate of bleeding-free survival (P = 0.028). CONCLUSION: For secondary prevention of stroke in patients with NVAF who are taking dabigatran etexilate, co-prescription with a statin was associated with a lower risk of bleeding complications. Future research is needed to determine the pharmacological mechanism underlying this effect.

Delayed diagnosis of atrial fibrillation after first-ever stroke increases recurrent stroke risk: a 5-year nationwide follow-up study.

BACKGROUND: Delayed detection of atrial fibrillation (AF) is common in patients with stroke. However, it is not well known whether delayed identification of AF in patients with stroke affects the prognosis of patients. AIMS: To evaluate the association between the timing of AF diagnosis after stroke and clinical outcomes. METHODS: We identified a cohort of all patients admitted with a primary diagnosis of first-ever ischaemic stroke, which was categorised into three groups, namely, non-AF, AF presenting with stroke and delayed AF diagnosis groups. The study patients were individually followed for 5 years to evaluate the occurrence of recurrent stroke and death. RESULTS: In total, 17 399 patients were hospitalised with first-ever ischemic stroke, of whom 16 261 constituted the non-AF group, 907 the AF presenting with stroke group and 231 the delayed AF diagnosis group. During the 5-year follow up, 2773 (17.1%), 175 (19.3%) and 68 (29.4%) patients in the non-AF, AF presenting with stroke and delayed AF diagnosis groups, respectively, were hospitalised for recurrent stroke. The delayed AF diagnosis group exhibited a 1.57-times higher risk of recurrent stroke than the AF presenting with stroke group, after adjustment for the CHA2DS2-VASc scores (adjusted hazard ratio (HR): 1.57; 95% confidence interval (CI) = 1.19-2.08; P = 0.002). In addition, delayed diagnosis of AF significantly increased the risk of recurrent stroke in men, but not in women, after adjustment for the CHA2DS2-VASc scores. CONCLUSION: Delayed diagnosis of AF after stroke increased the risk of recurrent stroke, particularly in men.

Clinical implication of hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator.

To determine the clinical implications of hemorrhagic transformation (HT) after thrombolysis, 241 eligible patients receiving alteplase for acute ischemic stroke were studied. HT was classified, according to the European Cooperative Acute Stroke Study criteria, as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH). Symptomatic intracranial hemorrhage (SICH) was defined according to the National Institute of Neurological Disorders and Stroke study. A novel classification, clinically significant intracranial hemorrhage (CSICH) was defined as HTs associated with an unfavorable clinical outcome (modified Rankin Scale 5-6) at 3 months. For all subtypes of HT, we found that patients receiving alteplase were more often in the standard-dose group (0.90 ± 0.02 mg/kg) than in the lower dose group (0.72 ± 0.07 mg/kg). PH and SICH were related to an unfavorable clinical outcome, while HI was not. There was a positive trend between age and CSICH in patients receiving the standard dose (P = 0.0101), and between alteplase dose and CSICH in patients ≥70 years old (P = 0.0228). All PHs (including asymptomatic PHs) and symptomatic HIs have been found to be associated with unfavorable outcome, and for this reason defined as CSICH. Independent predictors of CSICH were age ≥70 years and the standard dose of alteplase. Further studies of thrombolysis for ischemic stroke with different doses of alteplase are warranted.

Different doses of recombinant tissue-type plasminogen activator for acute stroke in Chinese patients.

BACKGROUND AND PURPOSE: The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. METHODS: A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. RESULTS: There was a significant trend for symptomatic intracerebral hemorrhage with age (P=0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage (P=0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome (P=0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage (P=0.0130) and less good functional outcome (P=0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality (P=0.0971) at 3 months in these patients. CONCLUSIONS: These results did not support the dose of 0.9 mg/kg of r-tPA being optimal for all patients in the East Asian population. In elderly patients (71-80 years), a lower dose of 0.6 mg/kg is associated with a better outcome. Confirmation of the results through randomized trial is required.

Intravenous Odatroltide for Acute Ischemic Stroke Within 24 Hours of Onset: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

Purpose: Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic stroke within 24 hours of onset. Patients and Methods: Patients with National Institutes of Health Stroke Scale (NIHSS 4-30) who were untreated with intravenous thrombolysis or endovascular thrombectomy were randomized (2:1) to receive a single dose of odatroltide (0.025 mg/kg) or placebo within 24 hours of stroke symptom onset. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) occurrence within 36 hours. Results: Twenty-four patients were enrolled and randomized; of these 16 and 8 received intravenous odatroltide infusion and placebo, respectively. sICH did not occur in both groups, and other safety measures were comparable between the groups. The rate of excellent functional outcome (modified Rankin Scale score, 0-1, at 90 days) was 21% and 14% in the odatroltide and placebo groups, respectively. Furthermore, 47% and 14% of patients in the odatroltide and placebo groups, respectively, showed major neurological improvement (NIHSS improvement ≥4 points from baseline to 30 days). Among the 9 odatroltide-treated patients with baseline NIHSS ≥6, 78% showed major neurological improvement. Conclusion: Compared with placebo, treatment with intravenous odatroltide within 24 hours following onset of ischemic stroke appears to be safe and may be associated with better neurological and functional outcomes. However, the efficacy and safety of odatroltide requires further confirmation in the next phase of clinical trials. Clinical Trial Registration: Clinicaltrials.gov identifier: NCT04091945.

Internal jugular venous abnormalities in transient monocular blindness.

BACKGROUND: The etiology of transient monocular blindness (TMB) in patients without carotid stenosis has been linked to ocular venous hypertension, for their increased retrobulbar vascular resistance, sustained retinal venule dilatation and higher frequency of jugular venous reflux (JVR). This study aimed to elucidate whether there are anatomical abnormalities at internal jugular vein (IJV) in TMB patients that would contribute to impaired cerebral venous drainage and consequent ocular venous hypertension. METHODS: Contrast-enhanced axial T1-weighted magnetic resonance imaging (MRI) was performed in 23 TMB patients who had no carotid stenosis and 23 age- and sex-matched controls. The veins were assessed at the upper IJV (at C1-3 level) and the middle IJV (at C3-5 level). Grading of IJV compression/stenosis was determined bilaterally as follows: 0 = normal round or ovoid appearance; 1 = mild flattening; 2 = moderate flattening; and 3 = severe flattening or not visualized. RESULTS: There was significantly more moderate or severe IJV compression/stenosis in the TMB patients at the left upper IJV level and the bilateral middle IJV level. Defining venous compression/stenosis scores ≥ 2 as a significant cerebral venous outflow impairment, TMB patients were found to have higher frequency of significant venous outflow impairment at the upper IJV level (56.5% vs. 8.7%, p = 0.0005) and the middle IJV level (69.6% vs. 21.7%, p=0.0011). CONCLUSIONS: TMB Patients with the absence of carotid stenosis had higher frequency and greater severity of IJV compression/stenosis which could impair cerebral venous outflow. Our results provide evidence supporting that the cerebral venous outflow abnormality is one of the etiologies of TMB.

Development of an Optically Induced Dielectrophoresis (ODEP) Microfluidic System for High-Performance Isolation and Purification of Bacteria.

For the rapid detection of bacteria in a blood sample, nucleic acid amplification-based assays are believed to be promising. Nevertheless, the nucleic acids released from the dead blood cells or bacteria could affect the assay performance. This highlights the importance of the isolation of live bacteria from blood samples. To address this issue, this study proposes a two-step process. First, a blood sample was treated with the immuno-magnetic microbeads-based separation to remove the majority of blood cells. Second, an optically induced dielectrophoresis (ODEP) microfluidic system with an integrated dynamic circular light image array was utilized to further isolate and purify the live bacteria from the remaining blood cells based on their size difference. In this work, the ODEP microfluidic system was developed. Its performance for the isolation and purification of bacteria was evaluated. The results revealed that the method was able to harvest the live bacteria in a high purity (90.5~99.2%) manner. Overall, the proposed method was proven to be capable of isolating and purifying high-purity live bacteria without causing damage to the co-existing cells. This technical feature was found to be valuable for the subsequent nucleic-acid-based bacteria detection, in which the interferences caused by the nontarget nucleic acids could be eliminated.

Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated.

Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway.

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

Triglyceride-Glucose Index and Intravenous Thrombolysis Outcomes for Acute Ischemic Stroke: A Multicenter Prospective-Cohort Study.

BACKGROUND: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT). METHODS: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3-6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4-8), moderate (9-15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores. RESULTS: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48-9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke. CONCLUSION: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity.

Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan.

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35-3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63-4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.

The p53/NF-kappaB-dependent induction of sestrin2 by amyloid-beta peptides exerts antioxidative actions in neurons.

Accumulation of senile plaques mainly composed of neurotoxic amyloid-beta peptide (Aß) is a pathological hallmark of Alzheimer's disease (AD). Sestrin2 inducible by various types of stressors is known to promote autophagy and exert antioxidative effects. In this work, we revealed the molecular mechanisms underlying Aß induction of sestrin2 and tested whether antioxidation, in addition to autophagy regulation, also contributes to its neuroprotective effects in primary rat cortical neurons. We found that Aß25-35 triggered nuclear translocation of p65 and p50, two subunits of nuclear factor-kappaB (NF-κB), and p53. Aß25-35-induced sestrin2 expression was abolished by the p65 siRNA, the NF-κB inhibitor SN50, and the p53 inhibitor pifithrin-alpha (PFT-α). Further, Aß25-35 enhanced binding of p50 and p53 to sestrin2 gene promoter that was abolished respectively by the p50 shRNA and PFT-α. Both p50 shRNA and PFT-α attenuated Aß25-35-induced expression as well as nuclear translocation of all three transcription factors, namely p65, p50, and p53. Interestingly, p50 binding to the promoters of its target genes required p53 activity, whereas p50 also negatively regulated p53 binding to its target sequences. Suppression of sestrin2 expression by siRNA enhanced Aß25-35- and Aß1-42-induced production of reactive oxygen species (ROS), lipid peroxidation, and formation of 8-hydroxy-2-deoxyguanosine (8-OH-dG). In contrast, overexpression of the sestrin2 N-terminal or C-terminal fragments neutralized Aß25-35-induced ROS production. We concluded that Aß-induced sestrin2 contributing to antioxidant effects in neurons is in part mediated by p53 and NF-κB, which also mutually affect the expression of each other.

Potential Roles of Sestrin2 in Alzheimer's Disease: Antioxidation, Autophagy Promotion, and Beyond.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

Corrigendum: Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience.

[This corrects the article DOI: 10.3389/fneur.2021.628077.].

Prevalence and Effect of Cerebral Small Vessel Disease in Stroke Patients With Aspirin Treatment Failure-A Hospital-Based Stroke Secondary Prevention Registry.

Background: Breakthrough strokes during treatment with aspirin, termed clinical aspirin treatment failure (ATF), is common in clinical practice. The burden of cerebral small vessel disease (SVD) is associated with an increased recurrent ischemic stroke risk. However, the association between SVD and ATF remains unclear. This study investigated the prevalence and clinical characteristics of SVD in stroke patients with ATF. Methods: Data from a prospective, and multicenter stroke with ATF registry established in 2018 in Taiwan were used, and 300 patients who developed ischemic stroke concurrent with regular use of aspirin were enrolled. White matter lesions (WMLs) and cerebral microbleeds (CMBs) were identified using the Fazekas scale and Microbleed Anatomical Rating Scale, respectively. Demographic data, cardiovascular comorbidities, and index stroke characteristics of patients with different WML and CMB severities were compared. Logistic regression analyses were performed to explore the factors independently associated with outcomes after ATF. Results: The mean patient age was 69.5 ± 11.8 years, and 70.0% of patients were men. Among all patients, periventricular WML (PVWML), deep WML (DWML), and CMB prevalence was 93.3, 90.0, and 52.5%, respectively. Furthermore, 46.0% of the index strokes were small vessel occlusions. Severe PVWMLs and DWMLs were significantly associated with high CMB burdens. Patients with moderate-to-severe PVWMLs and DWMLs were significantly older and had higher cardiovascular comorbidity prevalence than did patients with no or mild WMLs. Moreover, patients with favorable outcomes exhibited significantly low prevalence of severe PVWMLs (p = 0.001) and DWMLs (p = 0.001). After logistic regression was applied, severe WMLs predicted less favorable outcomes independently, compared with those with no to moderate PVWMLs and DWMLs [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.25-0.87 for severe PVWMLs; OR, 0.40; 95% CI, 0.21-0.79 for severe DWMLs]. Conclusions: SVD is common in stroke patients with ATF. PVWMLs and DWMLs are independently associated with functional outcomes in stroke patients with ATF. The burden of SVD should be considered in future antiplatelet strategies for stroke patients after ATF.

Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience.

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT). Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes. Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28-18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01-25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0-1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0-2 (adjusted OR: 1.39, 95% CI, 0.97-1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77-12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT. Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.

Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study.

BACKGROUND AND PURPOSE: The safety and efficacy of alteplase for ischemic stroke has not been examined in Chinese patients. We assessed the safety and efficacy of alteplase for acute ischemic stroke in daily clinical practice in Taiwan. METHODS: A prospective, multicenter, observational study was conducted in Taiwan from December 2004 to July 2008. Eligible patients (241) receiving alteplase were recruited and divided into 2 groups: standard dose (0.90 + or - 0.02 mg/kg, n=125) and lower dose (0.72 + or - 0.07 mg/kg, n=116). Primary outcome measures were safety: symptomatic intracerebral hemorrhage and death within 3 months. The secondary outcome measure was efficacy a modified Rankin scale of 0 to 2 after 3 months. RESULTS: The standard-dose group had higher rates of symptomatic intracerebral hemorrhage using National Institute of Neurological Diseases and Stroke, European Cooperative Acute Stroke Study, and Safe Implementation of Thrombolysis in Stroke-Monitoring Study definitions (10.4% versus 5.2%, 8.0% versus 2.6%, and 5.6% versus 1.7%, respectively) and mortality within 3 months (12.8% versus 6.9%), twice that of the lower-dose group. This pattern was more prominent in older patients. Significantly higher rates of symptomatic intracerebral hemorrhage per European Cooperative Acute Stroke Study (15.4% versus 3.3%, P=0.0257) and mortality (21.1% versus 5.0%, P=0.0099) and significantly lower independence rate (32.6% versus 53.6%, P=0.0311) were observed among patients > or = 70 years old receiving the standard dose than those receiving the lower dose. CONCLUSIONS: This study suggests that the standard dose of 0.9 mg/kg alteplase may not be optimal for treating aged Chinese patients. However, the dose of recombinant tissue plasminogen activator for ischemic stroke in Chinese patients should be based on more broad and convincing evidences and randomized trials of lower versus higher doses are needed.

Jugular venous reflux affects ocular venous system in transient monocular blindness.

BACKGROUND: The frequency of jugular venous reflux (JVR) is higher in patients with transient monocular blindness (TMB). We hypothesize that JVR influences ocular venous outflow, and resulting disturbances in cerebral and ocular venous circulation might be a cause of TMB. To substantiate this hypothesis, we aimed to demonstrate that: (1) TMB patients have vasculature changes in their retinal venules, and (2) JVR could influence ocular venous outflow, as revealed by dilated retinal venules. METHODS: This study has 2 parts. The case-control study included 31 TMB patients and 31 age/gender-matched normal individuals, who all received fundus photography for retinal venule diameter comparisons. The Valsalva maneuver (VM) experiment included 30 healthy volunteers who received both color Doppler imaging of the internal jugular vein and fundus photography for retinal venule diameter measurement. RESULTS: In the case-control study, TMB patients had a wider retinal venule diameter (184.5 +/- 17.5 vs. 174.3 +/- 16.2 microm, right eye, p = 0.023; 194.20 +/- 24.6 vs. 176.6 +/- 19.5 microm, left eye, p = 0.017), especially TMB patients with JVR. The VM experiments showed that the presence of JVR was associated with a greater increase in retinal venule diameters during VM in the subjects' right eye (14.27 +/- 11.16 vs. 2.75 +/- 3.51%, JVR vs. non-JVR, p = 0.0002) and left eye (10.06 +/- 6.42 vs. 1.80 +/- 2.03%, p = 0.0003). CONCLUSIONS: These findings provide evidence that frequently occurring JVR associated with TMB impedes ocular venous outflow, and the subsequent disturbances in ocular venous circulation may be a cause of TMB.

Different cerebral hemodynamic responses between sexes and various vessels in orthostatic stress tests.

OBJECTIVE: The argument about why the head-up tilt table test (HUT) does not include the posterior cerebral circulation, which is mainly responsible for syncope, as a monitor target has not been resolved. It is also unclear whether there is a sex difference in cerebral blood flow (CBF) changes. We hypothesized that orthostatic CBF changes more in the posterior circulation than in the anterior circulation and is different between sexes. METHODS: Thirty healthy volunteers (13 female and 17 male) were recruited for the HUT. The blood pressure (BP), middle cerebral artery flow velocity (MCAFV), and posterior cerebral artery flow velocity (PCAFV) were monitored simultaneously. Static cerebral autoregulation (CA) was calculated. RESULTS: The female volunteers had a lower BP, but there was no difference in orthostatic BP changes (female versus male: 1.29% +/- 5.26% versus 4.22% +/- 12.65%; P = .65). The female volunteers had a significantly greater orthostatic drop in the PCAFV than in the MCAFV (23.8% +/- 9.1% versus 18.2% +/- 7.3%; P = .008). The static CA in the middle cerebral artery was better than in the posterior cerebral artery, although not significantly (13.6% +/- 34.8% versus - 2.8% +/- 12.2%; P = .15). CONCLUSIONS: Our study showed the different cerebral hemodynamic responses between anterior and posterior circulations and between sexes during the HUT. We conclude that HUT studies for syncope should include the posterior cerebral circulation, especially for female patients.