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.

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.

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.].

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.

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.

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.

Emerging Roles of Inhibitor of Differentiation-1 in Alzheimer's Disease: Cell Cycle Reentry and Beyond.

Inhibitor of DNA-binding/differentiation (Id) proteins, a family of helix-loop-helix (HLH) proteins that includes four members of Id1 to Id4 in mammalian cells, are critical for regulating cell growth, differentiation, senescence, cell cycle progression, and increasing angiogenesis and vasculogenesis, as well as accelerating the ability of cell migration. Alzheimer's disease (AD), the most common neurodegenerative disease in the adult population, manifests the signs of cognitive decline, behavioral changes, and functional impairment. The underlying mechanisms for AD are not well-clarified yet, but the aggregation of amyloid-beta peptides (Aßs), the major components in the senile plaques observed in AD brains, contributes significantly to the disease progression. Emerging evidence reveals that aberrant cell cycle reentry may play a central role in Aß-induced neuronal demise. Recently, we have shown that several signaling mediators, including Id1, hypoxia-inducible factor-1 (HIF-1), cyclin-dependent kinases-5 (CDK5), and sonic hedgehog (Shh), may contribute to Aß-induced cell cycle reentry in postmitotic neurons; furthermore, Id1 and CDK5/p25 mutually antagonize the expression/activity of each other. Therefore, Id proteins may potentially have clinical applications in AD. In this review article, we introduce the underlying mechanisms for cell cycle dysregulation in AD and present some examples, including our own studies, to show different aspects of Id1 in terms of cell cycle reentry and other signaling that may be crucial to alter the neuronal fates in this devastating neurodegenerative disease. A thorough understanding of the underlying mechanisms may provide a rationale to make an earlier intervention before the occurrence of cell cycle reentry and subsequent apoptosis in the fully differentiated neurons during the progression of AD or other neurodegenerative diseases.

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.

Roles of Id1/HIF-1 and CDK5/HIF-1 in cell cycle reentry induced by amyloid-beta peptide in post-mitotic cortical neuron.

One neurotoxic mechanism of amyloid-beta peptide (Aß), the major component of senile plaques in the brains of Alzheimer's disease (AD) patients, is to trigger cell cycle reentry in fully differentiated neurons. However, the detailed underlying mechanisms remain unclear. Using Aß25-35-treated primary rat cortical neurons as the experimental system, in the present study we tested whether Aß-induced inhibitor of differentiation-1 (Id1)/hypoxia-inducible factor-1alpha (HIF-1α) and cyclin-dependent kinase-5 (CDK5) contribute to cell cycle reentry in fully differentiated post-mitotic neurons. We found that Id1-induced HIF-1α mediated Aß25-35-dependent expression of the cell cycle markers cyclin D1 and proliferating cell nuclear antigen (PCNA), both colocalized with microtubule-associated protein-2 (MAP-2) + cells, indicative of cell cycle reentry in the mature neurons. Aß25-35 also enhanced p35 cleavage to p25 without affecting CDK5 expression. The CDK5 inhibitor roscovitine and the siRNA targeting CDK5 both suppressed Aß25-35-dependent HIF-1α expression and cell cycle reentry. Intriguingly, Aß25-35-induced Id1 repressed p25 production while CDK5/p25 reciprocally inhibited Id1 expression, despite the observation that both Id1 and CDK5/p25 acted upstream of HIF-1α. These results demonstrated that both Id1/HIF-1 and CDK5/HIF-1 contribute to Aß-induced cell cycle reentry in post-mitotic neurons; furthermore, Id1 and CDK5/p25 reciprocally suppress expression of each other.

Low-dose versus standard-dose intravenous alteplase for octogenerian acute ischemic stroke patients: A multicenter prospective cohort study.

BACKGROUND AND PURPOSE: The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. METHODS: The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24-36 h of intravenous alteplase were measured. The baseline NIHSS of 4-8, 9-13, ≥14 were defined as mild, moderate, and high severity, respectively. RESULTS: Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). CONCLUSIONS: Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians.

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.

Transient Global Amnesia Linked to Impairment of Brain Venous Drainage: An Ultrasound Investigation.

Background: Previous neuroimaging and ultrasound studies suggested that compression and stenosis of the internal jugular vein (IJV) in patients with transient global amnesia (TGA) may impair IJV drainage, while a patent IJV releases intracranial pressure caused by the Valsalva maneuver (VM). Methods: Seventy-nine TGA patients with complete ultrasound examination data during admission were recruited prospectively to evaluate IJV drainage, which included the time-averaged mean velocity, and the cross-sectional lumen area of the IJV at the vein's middle (J2) and distal (J3) segments and the cross-sectional area during a 10-s VM to test for any retrograde or anti-grade flow. Forty-five TGA patients and 45 age- and sex-matched control subjects underwent complete contrast-enhanced magnetic resonance (MR) venous studies, which included time-resolved imaging of contrast kinetics, contrast-enhanced axial T1-weighted MR imaging, and phase-contrast-based non-contrast enhanced magnetic resonance venography (MRV). Results: In those subjects with complete MRV studies, the flow volumes exhibited at both the J2 and J3 segments of the left IJV and left vertebral vein (VV) were significantly lower in the TGA patients than in the control subjects. Although there was no significant difference in the flow volume of right IJV, the total of bilateral IJV, and VV flow volumes was still significantly lower in the TGA patients. As compared with the control subjects, the TGA patients exhibited significantly higher prevalence of completely blocked right IJV drainage at the J3 segment during the VM, but non-significantly higher for the left IJV at the J3 segment and for the right IJV at the J2 segment. Conclusion: Our results confirmed that the total venous flow decreases in the IJVs and VVs of the patients with TGA. This is consistent with the findings of previous MR imaging studies that have reported about compression and stenosis of the draining veins. We also found that IJV drainage is relatively compromised during the VM in the patients with TGA.

Id1 and Sonic Hedgehog Mediate Cell Cycle Reentry and Apoptosis Induced by Amyloid Beta-Peptide in Post-mitotic Cortical Neurons.

Amyloid beta-peptide (Aß), the neurotoxic component of senile plaques in Alzheimer's disease (AD) brains, is known to trigger cell cycle reentry in post-mitotic neurons followed by apoptosis. However, the underlying mechanisms remain unclear. Recently, we have reported that Aßs stimulate the expression of inhibitor of differentiation-1 (Id1) to induce sonic hedgehog (SHH) (Hung et al., Mol Neurobiol 53(2):793-809, 2016), and both are mitogens capable of triggering cell cycle progression. In this work, we tested the hypothesis that Aß-induced Id1 and SHH contribute to cell cycle reentry leading to apoptosis in neurons. We found that Aß triggered cell cycle progression in the post-mitotic neurons, as indicated by the increased expression of two G1-phase markers including cyclin D1 and phosphorylated retinoblastoma protein (pRb), two G2-phase markers such as proliferating cell nuclear antigen (PCNA) and incorporation of 5-bromo-2'-deoxyuridine (BrdU) into newly synthesized DNA, as well as the mitotic marker histone H3 phosphorylated at Ser-10. As expected, Aß also enhanced caspase-3 cleavage in the cortical neurons. Id1 siRNA, the neutralization antibody against SHH (SHH-Ab), and the cyclin-dependent kinase (CDK)-4/6 inhibitor PD0332991 all attenuated, in part or in full, the Aß-induced expression of these cell cycle markers. Indeed, exogenous recombinant Id1 protein and the biologically active N-terminal fragment of SHH (SHH-N) were both sufficient to enhance the expression of cell cycle markers independent of Aß. Taken together, our results revealed the critical roles of Id1 and SHH mediating Aß-dependent cell cycle reentry and subsequently caspase-dependent apoptosis in the fully differentiated post-mitotic neurons, at least in vitro.

Low Cholesterol Levels Increase Symptomatic Intracranial Hemorrhage Rates After Intravenous Thrombolysis: A Multicenter Cohort Validation Study.

AIM: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. METHODS: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24-36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. RESULTS: For enrolled 1845 patients, SICH rates were ≥2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281-0.846], p=0.0106), the ECASS II (adjusted RR: 0.318 [0.130-0.776], p=0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048-0.957], p=0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of ＜130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24-36 h. CONCLUSIONS: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of ＜130 mg/dL is supposed to a candidate marker for predicting SICH within 24-36 h.

Hyperglycemia predicts unfavorable outcomes in acute ischemic stroke patients treated with intravenous thrombolysis among a Chinese population: A prospective cohort study.

BACKGROUND AND PURPOSE: Poorly controlled blood glucose was reported to cause deterioration of acute ischemic stroke. In this study, we investigated whether an elevated admission serum glucose level in the 3-h time window of intravenous thrombolysis for acute ischemic stroke determined poor functional outcomes among Chinese population. METHODS: This was a prospective cohort study. From December 1, 2004 to December 31, 2016, a total of 2370 patients were enrolled and categorized into two cohorts by blood glucose levels of ≥200 and <200 mg/dl in the 3 h after stroke onset. The primary objective was to determine whether admission hyperglycemia increased major disability and death at 30 and 90 days, which was defined by a modified Rankin Scale of 3-6. The secondary objective was to determine whether admission hyperglycemia increased the symptomatic intracranial hemorrhage (SICH) at 90 days. The number needed to harm (NNH) and patient expected event rate (PEER) were evaluated for both the primary and secondary objectives. RESULTS: The primary outcome occurred in 216 of 305 patients (70.8%) in the blood glucose ≥200 mg/dl cohort and in 951 of 1587 patients (59.9%) in the blood glucose <200 mg/dl cohort at 30 days, and in 191 of 287 patients (66.6%) in the blood glucose ≥200 mg/dl cohort and in 827 of 1517 patients (54.5%) in the blood glucose <200 mg/dl cohort at 90 days. Patients with admission hyperglycemia had significantly increased major disability and death at 30 (adjusted relative risk (RR): 1.194 [1.073-1.329], p = 0.0012) and 90 days (adjusted RR: 1.203 [1.079-1.340], p = 0.0008). Admission hyperglycemia increased the risk of the occurrence of SICH by nearly 2-fold (adjusted RR: 1.891 [0.977-3.657], p = 0.0585 with the SITS-MOST criteria and adjusted RR: 1.884 [1.138-3.121], p = 0.0139 with the NINDS criteria). NNH values of admission hyperglycemia in major disability and death at 30 and 90 days were 9 and 10, and NNH values of SICH by the SITS-MOST NINDS criteria were 44 and 34, respectively. CONCLUSIONS: The study evidenced the association and temporal relationship of admission hyperglycemia causing deterioration of functional outcomes and increased SICH among Chinese population with acute ischemic stroke treated with intravenous thrombolysis.

Three years of the nationwide post-acute stroke care program in Taiwan.

Prolonged hospital stay and readmission are prevalent problems for stroke patients in Taiwan after the acute stage, partly due to the unmet need of post-acute care. In March 2014, Taiwan's National Health Insurance Administration launched a nationwide Post-Acute Care-CerebroVascular Disease (PAC-CVD) program. The Taiwan Stroke Society, coordinating 11 allied disciplines, took responsibility for the preparation and implementation of the program. As of June 2016, 6839 consecutive stroke patients were enrolled. On discharge from the PAC program, the functional status had improved in 87.5% of patients, with a significant decrease in the mean modified Rankin Scale score from 3.7 to 3.0. The rates of readmission and mortality in the PAC group were also lower than in the control group. In conclusion, the Taiwan's PAC-CVD program is an innovative and essentially effective national program of post-acute stroke care. We believe such experience should be helpful for policy makers of stroke care worldwide.

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.