Effect of PEAR1, PTGS1 gene polymorphisms on the recurrence of aspirin-treated patients with ischemic stroke in the Han population of China: A 4-year follow-up study.

Platelet endothelial aggregation receptor 1 (PEAR1) and prostaglandin endoperoxide synthase 1 (PTGS1) polymorphisms can affect laboratory aspirin resistance. However, the impact of genetic polymorphisms on the recurrence of ischemic stroke (IS) patients treated with aspirin is not fully understood. This study aimed to examine the relationship between gene polymorphisms of PEAR1 and PTGS1 and IS recurrence in patients treated with aspirin. Peripheral blood samples were collected from 174 patients with nonrecurrent IS and 34 with recurrent IS after aspirin treatment. Follow-up was performed on all patients. PEAR1 rs12041331 and PTGS1 rs10306114 polymorphisms were determined using the PCR fluorescence probe method. And the correlations of them with the clinical characteristics were examined by multivariable logistic regression analysis. The distribution frequencies of PEAR1 rs12041331 and PTGS1 rs10306114 genotypes were in Hardy-Weinberg equilibrium, and there was no significant difference in the distribution of PEAR1 rs12041331 polymorphism. Compared to the nonrecurrent group, the AA genotype of the PTGS1 polymorphism was more frequent in the recurrent group (59.77% vs 35.29%, P = .003), and the A allele also showed a higher frequency than the G allele in the recurrent group (P = .001). Multivariable logistic regression analysis showed that smoking (OR = 5.228, 95% CI: 1.938-14.102, P = .001), coronary heart disease (OR = 4.754, 95% CI: 1.498-15.089, P = .008), and the polymorphism at PTGS1(A>G) AA/AG + GG (OR = 2.955, 95% CI: 1.320-6.616, P = .008) were independently associated with IS recurrence in Chinese patients. Our findings suggested that PTGS rs10306114 polymorphisms should receive more attention in the use of aspirin in patients with IS.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Assessing the Efficacy of ChatGPT Versus Human Researchers in Identifying Relevant Studies on mHealth Interventions for Improving Medication Adherence in Patients With Ischemic Stroke When Conducting Systematic Reviews: Comparative Analysis.

BACKGROUND: ChatGPT by OpenAI emerged as a potential tool for researchers, aiding in various aspects of research. One such application was the identification of relevant studies in systematic reviews. However, a comprehensive comparison of the efficacy of relevant study identification between human researchers and ChatGPT has not been conducted. OBJECTIVE: This study aims to compare the efficacy of ChatGPT and human researchers in identifying relevant studies on medication adherence improvement using mobile health interventions in patients with ischemic stroke during systematic reviews. METHODS: This study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Four electronic databases, including CINAHL Plus with Full Text, Web of Science, PubMed, and MEDLINE, were searched to identify articles published from inception until 2023 using search terms based on MeSH (Medical Subject Headings) terms generated by human researchers versus ChatGPT. The authors independently screened the titles, abstracts, and full text of the studies identified through separate searches conducted by human researchers and ChatGPT. The comparison encompassed several aspects, including the ability to retrieve relevant studies, accuracy, efficiency, limitations, and challenges associated with each method. RESULTS: A total of 6 articles identified through search terms generated by human researchers were included in the final analysis, of which 4 (67%) reported improvements in medication adherence after the intervention. However, 33% (2/6) of the included studies did not clearly state whether medication adherence improved after the intervention. A total of 10 studies were included based on search terms generated by ChatGPT, of which 6 (60%) overlapped with studies identified by human researchers. Regarding the impact of mobile health interventions on medication adherence, most included studies (8/10, 80%) based on search terms generated by ChatGPT reported improvements in medication adherence after the intervention. However, 20% (2/10) of the studies did not clearly state whether medication adherence improved after the intervention. The precision in accurately identifying relevant studies was higher in human researchers (0.86) than in ChatGPT (0.77). This is consistent with the percentage of relevance, where human researchers (9.8%) demonstrated a higher percentage of relevance than ChatGPT (3%). However, when considering the time required for both humans and ChatGPT to identify relevant studies, ChatGPT substantially outperformed human researchers as it took less time to identify relevant studies. CONCLUSIONS: Our comparative analysis highlighted the strengths and limitations of both approaches. Ultimately, the choice between human researchers and ChatGPT depends on the specific requirements and objectives of each review, but the collaborative synergy of both approaches holds the potential to advance evidence-based research and decision-making in the health care field.

The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia­induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1.

In our previous study, we concluded that sirtuin 5 (SIRT5) was highly expressed in microglia following ischaemic stroke, which induced excessive neuroinflammation and neuronal injury. Therefore, SIRT5-targeting interventions should reduce neuroinflammation and protect against ischaemic brain injury. Here, we showed that treatment with a specific SIRT5 inhibitor, MC3482, alleviated microglia-induced neuroinflammation and improved long-term neurological function in a mouse model of stroke. The mice were administrated with either vehicle or 2 mg/kg MC3482 daily for 7 days via lateral ventricular injection following the onset of middle cerebral artery occlusion. The outcome was assessed by a panel of tests, including a neurological outcome score, declarative memory, sensorimotor tests, anxiety-like behavior and a series of inflammatory factors. We observed a significant reduction of infarct size and inflammatory factors, and the improvement of long-term neurological function in the early stages during ischaemic stroke when the mice were treated with MC3482. Mechanistically, the administration of MC3482 suppressed the desuccinylation of annexin-A1, thereby promoting its membrane recruitment and extracellular secretion, which in turn alleviated neuroinflammation during ischaemic stroke. Based on our findings, MC3482 offers promise as an anti-ischaemic stroke treatment that targets directly the disease's underlying factors.

Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke.

In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood-brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs).

Targeting pyroptosis to treat ischemic stroke: From molecular pathways to treatment strategy.

Ischemic stroke is the primary reason for human disability and death, but the available treatment options are limited. Hence, it is imperative to explore novel and efficient therapies. In recent years, pyroptosis (a pro-inflammatory cell death characterized by inflammation) has emerged as an important pathological mechanism in ischemic stroke that can cause cell death through plasma membrane rupture and release of inflammatory cytokines. Pyroptosis is closely associated with inflammation, which exacerbates the inflammatory response in ischemic stroke. The level of inflammasomes, GSDMD, Caspases, and inflammatory factors is increased after ischemic stroke, exacerbating brain injury by mediating pyroptosis. Hence, inhibition of pyroptosis can be a therapeutic strategy for ischemic stroke. In this review, we have summarized the relationship between pyroptosis and ischemic stroke, as well as a series of treatments to attenuate pyroptosis, intending to provide insights for new therapeutic targets on ischemic stroke.

Persistent Inequities in Intravenous Thrombolysis for Acute Ischemic Stroke in the United States: Results From the Nationwide Inpatient Sample.

BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy.

Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions. Additionally, the review delves into recent developments in the use of liposomes in ischemic stroke models, offering a comparative evaluation with other nanocarriers like exosomes and nano-micelles, thereby facilitating their clinical advancement.

Isobavachalcone alleviates ischemic stroke by suppressing HDAC1 expression and improving M2 polarization.

Ischemic stroke is a serious cerebrovascular condition. Isobavachalcone (ISO) has been documented to exhibit an anti-inflammatory effect across a variety of diseases; however, its protective impact on ischemic stroke remains unexplored. In this study, we evaluated the influence of ISO in both transient middle cerebral artery occlusion/reperfusion (tMCAO/R) rat models and oxygen-glucose deprivation/reperfusion (OGD/R) cell models. We observed that pretreatment with 50 mg/kg ISO diminished the volume of brain infarction, reduced brain edema, and ameliorated neurological deficits in rats. A reduction in Nissl bodies was noted in the tMCAO/R group, which was reversed following treatment with 50 mg/kg ISO. TUNEL/NeuN double staining revealed a decrease in TUNEL-positive cells in tMCAO/R rats treated with ISO. Furthermore, ISO treatment suppressed the expression of cleaved caspase-3 and BAX, while elevating the expression of BCL-2 in tMCAO/R rats. The levels of CD86 and iNOS were elevated in tMCAO/R rats; conversely, ISO treatment enhanced the expression of CD206 and Arg-1. Additionally, the expression of TNF-α, IL-6, and IL-1ß was elevated in tMCAO/R rats, whereas ISO treatment counteracted this effect. ISO treatment also increased the expression of TGF-ß and IL-10 in the ischemic penumbra of tMCAO/R rats. It was found that ISO treatment hindered microglial M1 polarization and favored M2 polarization. Histone Deacetylase 1 (HDAC1) is the downstream target protein of ISO, with ISO treatment resulting in decreased HDAC1 expression in both tMCAO/R rats and OGD/R-induced cells. Overexpression of HDAC1 was shown to promote microglial M1 polarization and inhibit M2 polarization in OGD/R+ISO cells. Overall, ISO treatment mitigated brain damage following ischemic stroke by promoting M2 polarization and attenuated ischemic injury by repressing HDAC1 expression.

Sex differences in treatment effect in neuroprotectant trials for acute ischemic stroke: A systematic review.

BACKGROUND: Pre-clinical data suggest sex differences in mechanisms of cerebral ischemic injury. This might result in differential outcomes of putative neuroprotectants by sex, though little systematic data is available to assess this. METHODS: We performed a systematic review of multicenter randomized controlled trials published from January 1980-June 2022 enrolling >100 subjects and testing neuroprotectants in acute ischemic stroke (AIS). For each trial, reported treatment effect by sex was extracted. When published results by sex were not available, we contacted individual authors to attempt to retrieve these data. RESULTS: We identified 59 publications reporting 64 trials that met inclusion criteria. Of these, data on treatment effect by sex were published for 14/64 trials. Unpublished data for an additional 5 trials were obtained from trial investigators (19/64, or 29.7%). Two trials (one testing uric acid and one dexborneol) reported treatment benefit in women but not men. Pooled analysis of six trials of tirilazad reported worse treatment outcomes in women and no effect in men. No clear difference was apparent in the other trials. CONCLUSIONS: Most trials did not report treatment effect by sex. Of those that did, there was little evidence of systematic sex differences in treatment response.

Contrast extravasation mimicking intracerebral and intraventricular hemorrhage after intravenous thrombolytic treatment of ischemic stroke: a case report.

BACKGROUND: Although contrast extravasation on follow-up head computed tomography (CT) is frequently visualized after endovascular treatment, this phenomenon is rare after intravenous thrombolytic treatment in patients with acute ischemic stroke (AIS). Here, we report a case of contrast extravasation mimicking intracerebral hemorrhage (ICH) with intraventricular extension after intravenous thrombolytic treatment and computed tomography angiography (CTA). CASE PRESENTATION: A 52-year-old man presented with right-sided hemiparesis and hypoesthesia. Initial non-contrast head CT was negative for intracranial hemorrhage and acute ischemic changes. He received intravenous treatment with tenecteplase 3.8 h after the onset of stroke. CTA of the head and neck was performed at 4.3 h after stroke onset. It showed no stenosis or occlusion of the carotid and major intracranial arteries. At about 1.5 h after CTA, the right-sided hemiparesis deteriorated, accompanied by drowsiness, aphasia, and urinary incontinence. Immediate head CT showed hyperdense lesions with mild space-occupying effect in the left basal ganglia and both lateral ventricles. The hyperdense lesions were reduced in size on follow-up CT after 5 h. Two days later, CT showed that the hyperdense lesions in the lateral ventricles almost completely disappeared and only a small amount remained in the infarcted area. CONCLUSIONS: Contrast extravasation into the brain tissue and lateral ventricles, mimicking ICH with intraventricular extension, could occur after intravenous thrombolytic treatment and CTA in a patient with AIS, which might lead to misdiagnosis and wrong treatment of the patient. The rapid resolution of intracranial hyperdense lesions is key to differentiate contrast extravasation from ICH on serial non-enhanced CT.

Ticagrelor Versus Clopidogrel in Acute Large-Vessel Ischemic Stroke: A Randomized Controlled Single-Blinded Trial.

BACKGROUND: Large-vessel ischemic stroke represents about 25-40% of all ischemic strokes. Few clinical trials compared ticagrelor versus clopidogrel in ischemic stroke patients; all these studies included only patients with a transient ischemic attack or minor stroke; moreover, none of these studies included patients from North Africa. OBJECTIVES: We aimed to compare ticagrelor versus clopidogrel in the first-ever large-vessel occlusion (LVO) acute ischemic stroke in Egypt. METHODS: Our trial involved 580 first-ever LVO ischemic stroke patients who were randomly assigned to administer loading and maintenance doses of ticagrelor or clopidogrel. Screening, randomization, and start of treatment occurred during the first 24 hours of the stroke. RESULTS: 580 patients were included in the intention-to-treat analysis. Thirty patients in the ticagrelor group and 49 patients in the clopidogrel group experienced a new ischemic or hemorrhagic stroke at 90 days (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38-0.98; p-value = 0.04), 36 patients in the ticagrelor group, and 57 in the clopidogrel group experienced composite of a new stroke, myocardial infarction, or death due to vascular insults (HR 0.56; 95% CI 0.37-0.87; p = 0.009). Patients who received ticagrelor had better clinical outcomes regarding National Institutes of Health Stroke Scale (NIHSS) reduction and a favorable modified Rankin scale (mRS) score. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. CONCLUSION: Patients with acute large-vessel ischemic stroke who received ticagrelor within the first 24 hours after ischemic stroke had better clinical outcomes based on recurrent stroke rates, NIHSS reduction, and favorable mRS rates compared with those who received clopidogrel. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications. TRIAL REGISTRATION: Clinical trials.gov (NCT06120725).

Risk and benefit of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding. MATERIALS AND METHODS: A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software. RESULTS: The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15). CONCLUSIONS: Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of all-cause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials.

Risk Factors Associated With Exclusion of Obese Patients Ischemic Stroke With a History of Smoking From Thrombolysis Therapy.

The objective of this study is to determine risk factors that may contribute to exclusion decision from recombinant tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) with a combined current or history of smoking and obesity. This study was conducted on data from 5469 patients with AIS collected from a regional stroke registry. Risk factors associated with inclusion or exclusion from rtPA were determined using multivariate logistic regression analysis. The adjusted odds ratios and 95% confidence interval for each risk factor were used to predict the increasing odds of an association of a specific risk factor with exclusion from rtPA. In the adjusted analysis, obese patients with AIS with a history of smoking (current and previous) excluded from rtPA were more likely to present with carotid artery stenosis (OR = 0.069, 95% CI 0.011-0.442), diabetes (OR = 0.604, 95% CI 0.366-0.997), higher total cholesterol (OR = 0.975, 95% CI 0.956-0.995), and history of alcohol use (OR = 0.438, 95% CI 0.232-0.828). Higher NIHSS score (OR = 1.051, 95% CI 1.017-1.086), higher triglycerides (OR = 1.004, 95% CI 1.001-1.006), and higher high-density lipoprotein (OR = 1.028, 95% CI 1.000-1.057) were associated with the inclusion for rtPA. Our findings reveal specific risk factors that contribute to the exclusion of patients with AIS with a combined effect of smoking and obesity from rtPA. These findings suggest the need to develop management strategies to improve the use of rtPA for obese patients with AIS with a history of smoking.

The association of CYP2C19 LoF alleles with adverse clinical outcomes in stroke patients taking clopidogrel: An updated meta-analysis.

The aggregated risk of recurrent stroke in stroke/transient ischemic attack (TIA) patients carrying CYP2C19 LoF alleles who take clopidogrel has not been investigated recently, and the available research is limited. This study aimed to perform an updated meta-analysis to assess the association between CYP2C19 LoF alleles and the risk of recurrent stroke in patients taking clopidogrel. Databases were searched for the literature on eligible studies. The end points were recurrent stroke, composite vascular events, and bleeding events. Odds ratios (ORs) were calculated using RevMan software, where p < 0.05 was considered statistically significant. Patients carrying CYP2C19 LoF alleles who were treated with clopidogrel had a significantly increased risk of recurrent ischemic stroke compared with non-carriers (OR 2.18, 96% CI 1.80-2.63; p < 0.00001). The risk of recurrent stroke was only significantly different in Asian patients (OR 2.29, 96% CI 1.88-2.80; p < 0.00001) but not in patients of other ethnicities; however, there were a limited number of studies in other ethnic groups. Both observational studies (OR 2.83, 96% CI 2.20-3.65; p < 0.00001) and RCTs (OR 1.48, 96% CI 1.10-1.98; p = 0.009) found associations with a significantly increased risk of recurrent ischemic stroke. Asian stroke patients or TIA patients carrying CYP2C19 LoF alleles and taking clopidogrel were at a significantly higher risk of recurrent ischemic stroke than non-carriers. Significantly increased risk of recurrent ischemic stroke was found in both observational studies and RCTs.

Glucose Control and Risk of Symptomatic Intracerebral Hemorrhage Following Thrombolysis for Acute Ischemic Stroke: A SHINE Trial Analysis.

BACKGROUND AND OBJECTIVES: Baseline hyperglycemia is associated with worse outcomes in acute ischemic stroke (AIS), including higher risk of symptomatic intracerebral hemorrhage (sICH) following treatment with thrombolysis. Prospective data are lacking to inform management of post-thrombolysis hyperglycemia. In a prespecified analysis from the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial of hyperglycemic stroke management, we hypothesized that post-thrombolysis hyperglycemia is associated with a higher risk of sICH. METHODS: Hyperglycemic AIS patients <12 hours onset were randomized to intensive insulin (target range 80-130 mg/dL) vs standard sliding scale (80-179 mg/dL) over a 72-hour period, stratified by treatment with thrombolysis. Three board-certified vascular neurologists independently reviewed all sICH events occurring within 7 days, defined by neurologic deterioration of ≥4 points on the NIH Stroke Scale (NIHSS). Associations between blood glucose control and sICH were analyzed using logistic regression accounting for NIHSS, age, systolic blood pressure, onset to thrombolysis time, and endovascular therapy (odds ratios [OR], 95% CI). Additional analysis compared patients in a high-risk group (age older than 60 years and NIHSS ≥8) vs all others. Categorical variables and outcomes were compared using the χ2 test (p < 0.05). RESULTS: Of 1151 SHINE participants, 725 (63%) received thrombolysis (median age 65 years, 46% women, 29% Black, 18% Hispanic). The median NIHSS was 7, baseline blood glucose was 187 (interquartile range 153-247) mg/dL, and 80% were diabetic. Onset to thrombolysis time was 2.2 hours (1.6-2.9). Post-thrombolysis sICH occurred in 3.6% (3.0% intensive vs 4.3% standard glucose control, OR 1.10, 0.60-2.01, p = 0.697). In the first 12 hours, every 10 mg/dL higher glucose increased the odds of sICH (OR 1.08, 1.03-1.14, p = 0.004), and a greater proportion of glucose measures in the normal range (80-130 mg/dL) decreased the odds of sICH (0.89, 0.80-0.99, p = 0.030). These associations were strongest in the high-risk group (age older than 60 years and NIHSS ≥8). DISCUSSION: In this prespecified analysis from the SHINE trial, intensive insulin therapy was not associated with a reduced risk of post-thrombolysis sICH compared with standard sliding scale. However, early post-thrombolysis hyperglycemia was associated with a higher risk of sICH overall, particularly in older patients with more severe strokes. Further prospective research is warranted to address the risk of sICH in hyperglycemic stroke patients undergoing endovascular therapy. TRIAL REGISTRATION INFORMATION: NCT01369069.

[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

What does cognitive screening reveal about early cognitive performance following endovascular clot retrieval and intravenous thrombolysis in acute ischaemic stroke?

Background Little is known regarding cognitive outcomes following treatment with endovascular clot retrieval (ECR) and intravenous tissue plasminogen activator (t-PA). We aimed to determine if there were any differences on a measure of cognitive screening between patients treated with ECR, t-PA, and those who were managed conservatively. Methods The medical records of ischaemic stroke patients admitted to Monash Medical Centre between January 2019 and December 2019 were retrospectively reviewed. Information extracted from medical records included age, sex, National Institutes of Health Stroke Scale at presentation, location of occlusion, treatment type, medical history, and cognitive screening performance measured by the Montreal Cognitive Assessment (MoCA). Results Eighty-two patients met the inclusion criteria (mean age = 66.5 ± 13.9; 49 male, 33 female). Patients treated with ECR performed significantly better on the MoCA (n = 36, 24.1 ± 4.3) compared to those who were managed conservatively (n = 26, 20.7 ± 5.5). Performance for patients treated with t-PA (n = 20, 23.9 ± 3.5) fell between the ECR and conservative management groups, but they did not significantly differ from either. Conclusion Our retrospective chart review found that ischaemic stroke patients treated with ECR appear to perform better on cognitive screening compared to patients who are managed conservatively. We also found that patients treated with ECR and t-PA appear to have similar cognitive screening performances in the acute stages following ischaemic stroke, although this finding is likely to have been impacted by group differences in stroke characteristics and may reflect the possibility that the ECR group performed better than expected based on their stroke severity.