Predictors of Very Poor Outcome After Mechanical Thrombectomy in Older Patients with Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke due to large vessel occlusion. However, some elderly patients with recanalization have a very poor outcome, including vegetative state and mortality. This study evaluated predictors of very poor outcome at 3 months in older patients with stroke undergoing MT treatment. METHODS: We retrospectively collected data from consecutive stroke patients ≥80 years old undergoing MT between April 2018 and January 2021. A very poor outcome was defined as a modified Rankin Scale (mRS) score of 5 or 6 at 3-month follow-up. Multiple logistic regression analysis was performed to identify the predictors of very poor outcome at 3 months. RESULTS: The study enrolled 62 patients with a median age of 85.5 years (interquartile range: 82.0-89.0). Of patients, 35 (56.5%) had a very poor outcome at 3-month follow-up. Multiple logistic regression analysis identified female sex (odds ratio = 3.592, 95% confidence interval 1.047-12.319, P = 0.042) and stroke-associated pneumonia (odds ratio = 6.103, 95% CI 1.541-24.174, P = 0.010) as independent predictors of very poor outcome. CONCLUSIONS: In elderly stroke patients undergoing MT treatment, female sex and stroke-associated pneumonia were independent predictors of very poor outcome at 3 months.

The benefit of favorable venous outflow profile is mediated through reduced microvascular dysfunction in acute ischemic stroke.

INTRODUCTIONS: Venous outflow (VO) is emerging as a marker of microvascular integrity in acute ischemic stroke. Using hemorrhagic transformation (HT) and infarct growth as mediators, we tested whether a favorable VO profile benefited functional outcome by reducing consequences of microvascular dysfunction. PATIENTS AND METHODS: Patients receiving thrombectomy in three comprehensive stroke centers due to acute anterior circulation occlusion were included. VO was assessed semi-quantitatively by the opacification of ipsilateral vein of Labbé, Trolard and superficial middle cerebral vein. HT was graded on follow-up CT. Infarct growth volume (IGV) was the difference of final infarct volume and baseline core volume. The association of VO and functional independence (90-day modified Rankin Scale ⩽ 2) was examined by logistic regression. Mediation analysis was performed among VO, HT or IGV, and functional outcome in patients with or without recanalization, respectively. RESULTS: In 242 patients analyzed, VO was strongly correlated with functional independence and VO ⩾ 4 was defined favorable. In 175 patients recanalized, favorable VO was associated with a reduced risk of HT (OR = 0.82, 95% CI 0.71-0.95, p = 0.008), which accounted for 13.1% of the association between VO and favorable outcome. In 67 patients without recanalization, favorable VO was associated with decreased IGV (ß = -0.07, 95% CI -0.11 to -0.02, p = 0.007). The association of favorable VO and functional independence was no longer significant (aOR = 4.84, 95% CI 0.87-38.87, p = 0.089) after including IGV in the model, suggesting a complete mediation. DISCUSSION AND CONCLUSION: In patients with acute anterior large vessel occlusion, the clinical benefit of VO may be mediated through reduced microvascular dysfunction.

Elevated ApoB/ApoA-Ι ratio is associated with poor outcome in acute ischemic stroke.

BACKGROUND: Apolipoproteins are known atherogenic factors that play important roles in many mechanisms related to acute ischemic stroke (AIS). However, it is unclear whether the ApoB/ApoA-Ι ratio is related to the prognosis of patients with AIS. METHODS: We conducted a prospective cohort study in the Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University and investigated the association between ApoB/ApoA-Ι ratio and poor outcomes at 3 months of AIS. RESULTS: 1,247 patients that met the eligibility criteria were enrolled in our study. We found that ApoA-Ι (Adjusted odds ratios (adjOR) 0.529, 95 %CI 0.327-0.855), ApoB (adjOR 3.015, 95 %CI 1.746-5.207), and ApoB/ApoA-Ι ratio (adjOR 3.986, 95 %CI 2.220-7.155) were independently associated with poor outcomes in acute ischemic stroke. During subgroup analysis, the ApoB/ApoA-Ι ratio was more likely associated with poor AIS outcomes in males and patients younger than 80 with SAO(Small Artery Occlusion) and no history of diabetes or statin use. Restricted cubic spline analyses explored the correlation between poor outcomes and ApoB/ApoA-Ι ratio. CONCLUSIONS: Higher ApoB, lower ApoA-Ι, and higher ApoB/ApoA-Ι ratios were independently associated with poor outcomes in AIS. However, ApoB and ApoA-Ι were not related to hemorrhagic transformation in AIS.

Red cell distribution width is associated with stroke severity and unfavorable functional outcomes in ischemic stroke.

Background: Red blood cell distribution width (RDW) is considered to be related to coronary heart disease and heart failure and all-cause mortality, but its relationship with acute ischemic stroke is still unclear. In this study, we aimed to explore the relationship between RDW and the stroke severity and functional outcomes of ischemic stroke. Methods: We retrospectively reviewed patients with acute ischemic stroke between September 2016 and January 2020. Demographic, clinical, stroke complications, laboratory data, and treatment were collected for all patients. Stroke severity and functional outcomes were evaluated by NIHSS score, modified Rankin Scale (mRS), and Barthel Index (BI) at 3 months. Furthermore, multiple logistic regression analysis was used to assess the relationship between RDW and stroke severity and functional outcomes. Results: A total of 629 patients with acute ischemic stroke were included and were categorized into four groups according to the quartiles of RDW (< 12.4, 12.4-12.9, 13.0-13.4, > 13.4). After multivariable analysis, higher RDW was directly associated with moderate to severe stroke (OR 2.21, 95% CI, 1.30-3.75, P = 0.003), mRS score of 3-6 at 3 months (OR 1.86, 95% CI, 1.02-3.41, P = 0.044), and BI score below 85 at 3 months (OR 2.27, 95% CI, 1.25-4.12, P = 0.007) in patients with ischemic stroke. Conclusion: Our results demonstrate that RDW is associated with stroke severity and unfavorable functional outcomes at 3 months in patients with ischemic stroke.

Nomogram to predict 3-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. METHODS: We analyzed 258 patients with acute ischemic stroke who underwent MT from January 2018 to February 2021. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3-6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter's Z-test to assess the calibration performance of the risk prediction model. RESULTS: In our visual nomogram, gender (odds ratio [OR], 3.40; 95%CI, 1.54-7.54), collateral circulation (OR, 0.46; 95%CI, 0.28-0.76), postoperative mTICI (OR, 0.06; 95%CI, 0.01-0.50), stroke-associated pneumonia (OR, 5.76; 95%CI, 2.79-11.87), preoperative Na (OR, 0.82; 95%CI, 0.72-0.92) and creatinine (OR, 1.02; 95%CI, 1.01-1.03) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT. The area under the nomogram curve was 0.8791 with good calibration performance (P = 0.873 for the Spiegelhalter's Z-test). CONCLUSIONS: A novel nomogram consisting of gender, collateral circulation, postoperative mTICI, stroke-associated pneumonia, preoperative Na and creatinine can predict the 3-month unfavorable outcomes in stroke patients treated with MT.

Expanding the clinical spectrum of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72 years old, and the disease duration ranged from 12 h to 25 years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.

Personalized antiplatelet therapy guided by clopidogrel pharmacogenomics in acute ischemic stroke and transient ischemic attack: A prospective, randomized controlled trial.

Background: Clopidogrel is frequently used in patients with ischemic stroke or transient ischemic attack (TIA), but its efficacy is hampered by inter-individual variability, due to genetic differences associated with clopidogrel metabolism. We conducted this randomized controlled trial to validate whether the personalized antiplatelet therapy based on clopidogrel pharmacogenomics and clinical characteristics leads to better clinical outcomes compared with standard treatment. Methods: Patients were randomly divided into the standard group or pharmacogenetic group, in which the pharmacogenetic group required the detection of the genotyping of CYP2C19*2, CYP2C19*3, and CYP2C19*17. Patients were followed up for 90 days for the primary efficacy endpoint of new stroke events, secondary efficacy endpoint of individual or composite outcomes of the new clinical vascular events, and the incidence of disability. The primary safety outcome was major bleeding. Results: A total of 650 patients underwent randomization, among which 325 were in the pharmacogenomics group while 325 were in the standard group. Our study found after a 90-day follow-up, the risk of stroke and composite vascular events in the pharmacogenomics group was lower than that in the standard group. The incidence of disability significantly decreased in the pharmacogenomics group. In addition, no statistically significant differences were observed in bleeding events between the two groups. Conclusion: The present study demonstrates that personalized antiplatelet therapy guided by clopidogrel pharmacogenomics and clinical characteristics can significantly improve the net clinical benefit of ischemic stroke or TIA patients during the 90-day treatment period without increasing bleeding risk.

Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin.

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel. Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models. Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07-0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06-0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08-0.72, P = 0.03 for 7-day Barthel Index, respectively]. Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone. Clinical Registration Number: 1800019911.

An increase in neutrophil-to-lymphocyte ratio predicts poor functional outcomes in older patients with acute ischemic stroke: a retrospective study.

The neutrophil-to-lymphocyte ratio has emerged as a predictor of functional outcome in stroke patients. However, less is known about the value of neutrophil to lymphocyte ratio in older patients. This clinical study evaluated whether the neutrophil-to-lymphocyte ratio is associated with stroke severity and early clinical outcomes in older patients with acute ischemic stroke. This observational study included acute ischemic stroke patients aged 80 years or older. The patients were divided into three groups, and information was collected, including demographic, clinical and laboratory data. The neutrophil associations to lymphocyte ratio with stroke severity and early clinical outcomes were assessed with logistic regression. Overall, 356 older patients were enrolled in this study, with a median age of 85.0 (82.0-88.0). Split by tertiles of neutrophil-to-lymphocyte ratio, 118 patients were in the bottom tertile (<2.17), 118 patients were in the middle tertile (2.17-3.36), and 120 patients were in the top tertile (>3.36). After multivariable analysis, patients in the highest tertile were likely to have moderate to severe stroke on admission (OR 4.87, 95% CI, 1.93-12.30, P = 0.001), higher risks of primary unfavorable outcome (OR 2.70, 95% CI, 1.09-6.69, P = 0.032) and secondary unfavorable outcome (OR 2.00, 95% CI, 1.00-4.00, P = 0.050) compared to the lowest tertile. Our finding demonstrated that the neutrophil-to-lymphocyte ratio is an independent predictor of stroke severity and early clinical outcomes in older patients with acute ischemic stroke.

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Long-Term Cerebrovascular Outcomes in Patients With Minor Stroke or Transient Ischemic Attack.

Background: Platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 has been reported to affect agonist-stimulated platelet aggregation, but it remains unclear whether this variant plays a role in recurrent stroke. Here we assess the clinical relevance of PEAR1 rs12041331 in acute minor ischemic stroke (AMIS) and transient ischemic attack (TIA) Chinese patients treated with dual antiplatelet therapy (DAPT). Methods: We recruited 273 consecutive minor stroke and TIA patients, and Cox proportional hazard regression was used to model the relationship between PEAR1 rs12041331 and thrombotic and bleeding events. Results: Genotyping for PEAR1 rs12041331 showed 49 (18.0%) AA homozygotes, 129 (47.3%) GA heterozygotes, and 95 (34.7%) GG homozygotes. No association was observed between PEAR1 rs12041331 genotype and stroke or composite clinical vascular event rates (ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, or vascular death) or bleeding events regardless if individuals carried one or two copies of the A allele. Our results suggested that rs12041331 genetic polymorphism was not an important contributor to clinical events in AMIS and TIA patients in the setting of secondary prevention. Conclusions: Our data do provide robust evidence that genetic variation in PEAR1 rs12041331 do not contribute to atherothrombotic or bleeding risk in minor stroke and TIA patients treated with DAPT.

Inflammatory markers as independent predictors for stroke outcomes.

BACKGROUND: Inflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype. METHODS: A total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C-reactive protein (CRP), and interleukin-6 (IL-6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported. RESULTS: Neutrophil and WBC were significantly higher in large-artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small-artery occlusion (SAO). Neutrophil-lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes. CONCLUSION: Inflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.

Retinal Degeneration: A Window to Understand the Origin and Progression of Parkinson's Disease?

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, manifests with motor and non-motor symptoms associated with two main pathological hallmarks, including the deterioration of dopaminergic cells and aggregation of alpha-synuclein. Yet, PD is a neurodegenerative process whose origin is uncertain and progression difficult to monitor and predict. Currently, a possibility is that PD may be secondary to long lasting peripheral affectations. In this regard, it has been shown that retinal degeneration is present in PD patients. Although it is unknown if retinal degeneration precedes PD motor symptoms, the possibility exists since degeneration of peripheral organs (e.g., olfaction, gut) have already been proven to antedate PD motor symptoms. In this paper, we explore this possibility by introducing the anatomical and functional relationship of retina and brain and providing an overview of the physiopathological changes of retinal structure and visual function in PD. On the basis of the current status of visual deficits in individuals with PD, we discuss the modalities and pathological mechanism of visual function or morphological changes in the retina and focus on the correlation between visual impairment and some representative structural features with clinical significance. To consider retinal degeneration as a contributor to PD origin and progress is important because PD evolution may be monitored and predicted by retinal studies through state-of-the-art techniques of the retina. It is significant to integrally understand the role of retinal morphological and functional changes in the neurodegenerative process for the diagnosis and therapeutic strategies of PD.

Left Atrial Enlargement is Associated with Stroke Severity with Cardioembolic and Cryptogenic Subtypes in a Chinese Population.

BACKGROUND: Left atrial enlargement is associated with increased risk for stroke. However, few studies that evaluated the correlation between left atrial size and ischemic stroke severity. In this study, we aim to evaluate the association between left atrial size and stroke severity, especially with cardioembolic and cryptogenic stroke in the Chinese population. METHODS: A total of 1271 patients with acute ischemic stroke were included in this study. Echocardiographic left atrial diameter was measured and indexed to height. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate-to-severe neurologic deficit was defined as NIHSS greater than or equal to 5. Patients were divided into mild, moderate, or severe abnormal left atrial size by tertile distribution. Binary logistic regression analysis was used to identify independent predictors of severe stroke after adjustment. RESULTS: Among all enrolled patients, 328 (25.8%) were classified into moderate-to severe stroke severity (NIHSS ≥ 5). In the multivariable model, compared with the lowest tertile of left atrial size, the odds ratio for moderate-to-severe neurologic deficit was 0.902 (95% CI, 0.644-1.264, P = .550) when left atrial size was the highest tertile. Of all patients, 190 patients were further categorized as cardioembolic and cryptogenic subtypes, and 70 (36.8%) were classified into moderate-to-severe stroke severity. After adjusting for confounders, compared with the lowest tertile, the top tertile of left atrial size was significantly associated with moderate-to-severe stroke (3.156, 95% CI, 1.143-8.711, P = .027). CONCLUSION: Left atrial enlargement was associated with more severe initial neurologic deficits of embolic subtypes (cardioembolic and cryptogenic stroke) in patients with acute ischemic stroke.

Intracranial Aneurysms After Intravenous Thrombolysis in Patient with Atrial Myxoma: A Case Study.

We administered intravenous thrombolytic therapy to a 51-year-old female patient with a 101-min stroke onset. The patient was unconscious during the manifestation of symptoms. Computed tomography angiography examination of the intracranial artery at the time of admission suggested that the left middle cerebral artery was occluded. The patient regained consciousness after the intravenous thrombolytic treatment was administered. On an urgent cerebral angiography, it was revealed that the recanalization of the left middle cerebral artery was successful. Although blood perfusion was restored, occlusion of the distal blood flow remained. The symptoms of the patient gradually improved after the treatment. However, 6 months after the onset of the condition, intracranial aneurysms formed distal to the recanalized arteries that were previously embolized. The full process underlying the development of cerebral embolism caused by atrial myxomas and subsequent formation of aneurysms is illustrated in this patient. Although the underlying mechanism remains unclear, intravenous thrombolysis can successfully restore cerebral blood flow in and may improve the prognosis of patients with cerebral embolism caused by cardiac myxoma. Despite the positive revascularization therapy, the occurrence of the complication of intracranial aneurysms is possible. Long-term follow-up to evaluate the progression of myxomatous aneurysms after cerebral embolism with conservative treatment may be a suitable strategy for managing such patients.

Intracranial Atherosclerotic Disease-Related Acute Middle Cerebral Artery Occlusion Can Be Predicted by Diffusion-Weighted Imaging.

Background: The differentiation of large vessel occlusion caused by intracranial atherosclerotic stenosis (ICAS) or intracranial embolism significantly impacts the course of treatment (i.e., intravenous thrombolysis versus mechanical thrombectomy) for acute cerebral infarction. Currently, there is no objective evidence to indicate ICAS-related middle cerebral artery M1 segment occlusion before treatment. In cases of ICAS, it is often observed that the infarct core caused by ICAS-related M1 segment middle cerebral artery occlusion (MCAO) is located in deeper parts of the brain (basal ganglia or semiovoid region). Objective: To evaluate whether the location of the infarct core, identified using diffusion-weighted imaging (DWI), can be used to differentiate ICAS from intracranial embolism. Methods: Thirty-one consecutive patients diagnosed with acute cerebral infarction caused by middle cerebral artery M1 segment occlusion were retrospectively included based on angiographic findings to distinguish ICAS from embolic occlusion. Patients were divided into two groups based on the location of the infarct core on DWI: in the deep part of the brain (basal ganglia or semiovoid region) or more superficially (i.e., cortex). Results: In 16 patients, the infarct core was mainly in the deep part of the brain on DWI [14 of 16 patients in the ICAS group and only 2 in the non-ICAS group (93.3 vs. 6.7%, respectively; P < 0.001)]. The diagnostic sensitivity of DWI for ICAS was 93.3%, with a specificity of 87.5%, a Positive predictive value (PPV) of 87.5%, and an Negative predictive value (NPV) of 93.3%, the accuracy was 88.5%. Conclusion: Intracranial atherosclerotic disease-related acute MCAO can be predicted using DWI.

Personalised antiplatelet therapy based on pharmacogenomics in acute ischaemic minor stroke and transient ischaemic attack: study protocol for a randomised controlled trial.

INTRODUCTION: Antiplatelet therapy combining aspirin and clopidogrel is considered to be a key intervention for acute ischaemic minor stroke (AIMS) and transient ischaemic attack (TIA). However, the interindividual variability in response to clopidogrel resulting from the polymorphisms in clopidogrel metabolism-related genes has greatly limited its efficacy. To date, there are no reports on individualised antiplatelet therapy for AIMS and TIA based on the genetic testing and clinical features. Therefore, we conduct this randomised controlled trial to validate the hypothesis that the individualised antiplatelet therapy selected on the basis of a combination of genetic information and clinical features would lead to better clinical outcomes compared with the standard care based only on clinical features in patients with AIMS or TIA. METHODS AND ANALYSIS: This trial will recruit 2382 patients with AIMS or TIA who meet eligibility criteria. Patients are randomly assigned in a 1:1 ratio to pharmacogenetic group and standard group. Both groups receive a loading dose of 300 mg aspirin and 300 mg clopidogrel on day 1, followed by 100 mg aspirin per day on days 2-365. The P2Y12 receptor antagonist is selected by the clinician according to the genetic information and clinical features for pharmacogenetic group and clinical features for the standard group on days 2-21. The primary efficacy endpoint is a new stroke event (ischaemic or haemorrhagic) that happens within 1 year. The secondary efficacy endpoint is analysed as the individual or composite outcomes of the new clinical vascular event (ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death). Baseline characteristics and outcomes after treatment will be evaluated. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Yangpu Hospital, Tongji University School of Medicine (No. LL-2018-KY-012). We will submit the results of this trial for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR1800019911; Pre-results.

The association of serum lipid level with ischemic stroke in the elderly of Xinjiang.

BACKGROUND: The aim of the present study is to determine the association of serum lipid level in the above 55-year-old age elderly with ischemic stroke (IS) in Xinjiang regions, China. METHODS: 408 patients with IS and 347 healthy individuals as control in the ≥55-year-old elderly were selected for the present study in Xinjiang province of China from July 2010 to July 2012. Patients were divided into different groups according to the IS subtypes (large-artery atherosclerosis, LAA; cardio-aortic embolism CE; small-artery occlusion, SAO), plague stability, hypertension and diabetes. The serum lipid level including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), Lipoprotein(a) (Lp(a)) and their ratios(TC/HDL, LDL/HDL, ApoA1/ApoB) were measured. RESULTS: Patients in LAA group had higher ratio of TC/HDL, ApoA1/ApoB and lower level of ApoA1 than SAO group(p<0.05); higher level of TC, HDL, LDL, TC/HDL, LDL/HDL, ApoA1/ApoB and lower level of ApoB compared with CE group. Patients in SAO group had higher level of LDL, ApoA1, ApoB, TC/HDL, LDL/HDL and ApoA1/ApoB than CE group. Patients with stable plaque had higher level of HDL and low level of LDL, ApoB, Lp(a), TC/HDL, LDL/HDL and ApoA1/ApoB than unstable plaque group. Patients with hypertension had higher level of TG, ApoB, Lp(a), LDL/HDL and ApoA1/ApoB than non-hypertensive group. Patients with diabetes had higher level of TC, TG, ApoB, TC/HDL, LDL/HDL, ApoA1/ApoB and low level of ApoA1 than non-diabetic group. Multiple logistic regression analysis revealed that high LDL, ApoB, LDL/HDL and ApoA1/ApoB might be the risk factors for ischemic stroke. CONCLUSION: An abnormal serum lipid level of the patients with IS in older Xinjiang population is significantly associated with the stroke subtypes, plaque stability, hypertension and diabetes.

Clinical characteristics and risk score for poor clinical outcome of acute ischemic stroke patients treated with intravenous thrombolysis therapy.

BACKGROUND: Tissue plasminogen activator (t-PA) is an effective therapy for acute ischemic stroke, but some patients still have poor clinical outcome. In this study, we investigated clinical characteristics of stroke patients and determined predictors for poor clinical outcome in response to t-PA treatment. METHODS: Clinical data from 247 patients were retrospectively reviewed. Clinical parameters that were associated with survival of patients were analyzed. Areas under receiver operating characteristic curves (ROC) were used to determine the feasibility of using various combinations of the clinical parameters to predict poor clinical response. The clinical outcome was defined according to the changes in Modified Rankin Scale. RESULTS: Overall, 145 patients had improved/complete recovery, 73 had no change, and 29 had worsening conditions or died during the in-clinic period. A univariate analysis showed that baseline characteristics including age, CRP, blood glucose level, systolic blood pressure, and admission NIHSS were significantly different (p < 0.05) among patients with different clinical outcome. A further multivariate analysis was then performed. Variables associated with poor clinical outcome (worsening/death) (p < 0.1) were included in the logistic regression model. Four parameters were retained in the model: Age, CRP, Blood glucose level, and Systolic blood pressure (ACBS). To allow a convenient usage of the ACBS classifier, the parameters were put into a scoring system, and the score at 7.7 was chosen as a cut-off. The ROC curve of this ACBS classifier has an area under the curve (AUC) of 0.7788, higher than other individual parameters. The ACBS classifier provided enhanced sensitivity of 69.2% and specificity of 74.3%. CONCLUSION: The ACBS classifier provided a satisfactory power in estimating the patients' clinical outcome. After further validating, the classifier may provide important information to clinicians for making clinical decisions.

SUMOylation participates in induction of ischemic tolerance in mice.

A group of proteins, small ubiquitin-like modifier (SUMO) proteins, has been shown to play a major role in rodent cerebral ischemia. Here, we proved that transient global cerebral ischemia induces a marked increase in protein sumo2/3 conjugation levels, we also find that global sumo2/3 conjugation is involved in ischemic tolerance in mice. Mice preconditioned by sublethal ischemia were less vulnerable to severe ischemia than non-preconditioned mice. Five-minute BCCAO precondition decreased the levels of SUMO2/3-conjugated proteins induced by MCAO. These findings suggest that maintenance of a globally decreased SUMO2/3 (and maybe SUMO-2/3) conjugation level as revealed by immunoblot assays is a component of ischemic tolerance.

The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang.

BACKGROUND: The present study is aimed to evaluate difference of lipid metabolism related gene single nucleotide polymorphisms (SNPs) with ischemic stroke (IS) in Han and Uighur population of Xinjiang, China. METHODS: Four hundred eight patients with ischemic stroke and 347 unrelated healthy individuals of age and sex matched were genotyped for Apolipoprotein A5 (ApoA5), lipoprotein lipase (LPL), Cholesteryl ester transfer protein (CETP) and low-density lipoprotein receptor (LDL-R) genes. Their mutation difference was analyzed by SNaP shot techniques. GeneMapper4.1 SPSS20.0 software was used for data management and analysis. Using a single locus analysis, the distribution difference of genotype loci in ischemic stroke cases and controls were detected to assess the genetic risk factors of ischemic stroke. RESULTS: Significance differences of genotype distribution in ischemic stroke cases and controls were observed in LDLR rs688 in Han and Uighur population in recessive model from analysis of single gene locus. It also was found that dramatic difference of triglyceride (TG) of LPL rs328 and systolic blood pressure in CETP rs708277 of total population. In binary logistic regression analysis of total studied population, ischemic stroke was observed significantly associated with LDLR rs688 both addictive model (TT/CC, adjusted OR = 1.47, 95% CI = 1.04-2.07) and recessive model (TT/CT + CC, adjusted Odds ratio (OR) = 2.66, 95% Confidence Interval (CI) = 1.37-5.14). In Han population, ischemic stroke was observed significantly associated with rs688 both in addictive model (TT/CC, adjusted OR = 3.27, 95% CI = 1.06-10.05). In Uighur population, no significant association was found between gene polymorphisms and the risk of ischemic stroke. Combined analysis of multiple gene and loci, interaction effects of LDLR rs688 C/T, ApoA5 rs662799 A/G and CETP rs708272 C/T denoted a significant influence on IS susceptibility. CONCLUSION: Single nucleotide polymorphisms of lipid metabolism relative gene were significantly associated with the morbidity of ischemic stroke in Han population. The interaction effects of rs688 C/T with ApoA5 rs662799 A/G and CETP rs708272 C/T promoted the occurrence of IS.