Efficacy and safety of batroxobin in patients with acute ischemic stroke: A multicenter retrospective analysis.

AIMS: The objective of this study was to evaluate the effectiveness of batroxobin in improving functional outcomes and reducing stroke recurrence among patients with acute ischemic stroke beyond the therapeutic time window for thrombolytic therapy. METHODS: This multicenter, retrospective study enrolled 492 patients with acute moderate-to-severe ischemic stroke within 24 h. 238 patients were given standard (basic) therapy. On the basis of standard treatment, 254 patients received an initial intravenous infusion of batroxobin 10 U on day 1, followed by subsequent infusions of batroxobin 5 U on the 3rd and 5th days, respectively. RESULTS: In the batroxobin group, 8.3% of patients experienced recurrence stroke, compared to 17.2% in the control group (HR, 0.433; 95% CI, 0.248 to 0.757; p = 0.003). Furthermore, intravenous batroxobin significantly improved the distribution of 90-120 day disability. Moderate-to-severe bleeding events were reported in three patients (1.2%) in the batroxobin group and one patient (0.4%) in the control group (p = 0.369). CONCLUSIONS: Among patients with acute moderate-to-severe ischemic stroke beyond the time window for thrombolytic therapy, treatment with intravenous batroxobin had a lower risk of stroke recurrence and a better recovery of function outcome without increasing bleeding events. Prospective studies are needed to further confirm.

[Comparison of the effectiveness of non-immunogenic staphylokinase and alteplase for intravenous thrombolysis in ischemic stroke: analysis of hospital registry data]. / Sravnenie effektivnosti primeneniya neimmunogennoi stafilokinazy i alteplazy dlya vnutrivennogo trombolizisa pri ishemicheskom insul'te: analiz dannykh gospital'nogo registra.

OBJECTIVE: To compare the effectiveness and safety of the use of non-immunogenic staphylokinase (NS) and alteplase (AP) for intravenous thrombolysis (IT) for ischemic stroke (IS) in real clinical practice at a regional vascular center. MATERIAL AND METHODS: Data from 100 patients with IS who received IT with NS and 100 patients who received IT with AP for the period 2022-2023 were analyzed. The groups were comparable on sociodemographic parameters, cardiovascular risk factors and diseases, and stroke characteristics. RESULTS: Door-to-needle time was 17 (13-22) min in the NS group and 38 (33-42) min in the AP group (p<0.001). During control neuroimaging, a cerebral infarction was detected in 46% of patients in the NS group and 61% of patients in the AP group (OR 0.479 [0.263; 0.875], p=0.035). When performing IT with NS, an NIHSS score of 0 points (no neurological deficit) was observed twice as often (OR 2.202 [1.079; 4.504], p=0.023). The incidence of hemorrhagic transformation, including symptomatic, as well as hospital mortality did not differ. CONCLUSION: IT with NS is associated with a lower probability of cerebral infarction and greater positive dynamics of the neurological status in comparison with the use of AP already within the first stage of treatment and rehabilitation.

Ischaemic apoplexy caused by syphilis.

Syphilis is a sexually transmitted disease caused by the spirochaete Treponema pallidum. Patients with untreated syphilis can develop meningovascular syphilis at any stage of the disease. This is a case report of a 44-year-old man displaying two instances of acute vertigo and lateralized paraesthesia. MRI showed infarctions in the left thalamus and capsula interna. Subsequent investigations including cerebral spinal fluid analysis revealed a diagnosis of neurosyphilis. The patient was treated intravenously with benzylpenicillin and ceftriaxone with complete clinical remission.

Prognosis of Patients With Ischemic Stroke With Prior Anticoagulant Therapy: Direct Oral Anticoagulants Versus Warfarin.

BACKGROUND: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. METHODS AND RESULTS: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001). CONCLUSIONS: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.

Timing of Anticoagulation Resumption and Risk of Ischemic and Hemorrhagic Complications in Patients With ICH and Mechanical Heart Valves.

BACKGROUND AND OBJECTIVES: In patients with mechanical heart valves and recent intracranial hemorrhage (ICH), clinicians need to balance the risk of thromboembolism during the period off anticoagulation and the risk of hematoma expansion on anticoagulation. The optimal timing of anticoagulation resumption is unknown. We aimed to investigate the relationship between reversal therapy and ischemic stroke, between duration off anticoagulation and risk of ischemic strokes or systemic embolism and between timing of anticoagulation resumption and risk of rebleeding and ICH expansion. METHODS: We conducted a retrospective cohort observational study in 3 tertiary hospitals. Consecutive adult patients with mechanical heart valves admitted for ICH between January 1, 2000, and July 13, 2022, were included. The primary end points of our study were thromboembolic events (cerebral, retinal, or systemic) while off anticoagulation and ICH expansion after anticoagulation resumption (defined by the following criteria: increase by one-third in intracerebral hematoma volume, increase by one-third in convexity subdural hemorrhage diameter, or visually unequivocal expansion of other ICH locations to the naked eye). RESULTS: A total of 171 patients with mechanical heart valves who experienced ICH were included in the final analysis. Most of the patients (79.5%) received reversal therapy for anticoagulation. Patients who received anticoagulation reversal therapy did not have increased risk of thromboembolic complications. Time off anticoagulation was not associated with risk of ischemic stroke; only 2 patients had a stroke within 7 days of the ICH, and both had additional major risk factors of thromboembolism. The rate of ischemic stroke/transient ischemic attack while off anticoagulation was lower than the rate of ICH expansion once anticoagulation was resumed (6.4% vs 9.9%). Furthermore, patients who developed ICH expansion had higher mortality compared with patients who had ischemic stroke while being off anticoagulation (41% vs 9%). Use of intravenous heparin bridging upon resumption of warfarin was strongly associated with increased risk of ICH expansion as compared with restarting warfarin without a heparin bridge. DISCUSSION: Withholding anticoagulation for at least 7 days after ICH may be safe in patients with mechanical heart valves. Heparin bridging during anticoagulation resumption may be associated with increased risk of bleeding.

Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion.

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Correlation analysis of inflammatory markers with the short-term prognosis of acute ischaemic stroke.

Stroke is the second leading cause of death worldwide, and China has the highest stroke incidence in the world. The systemic inflammatory response index (SIRI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-high-density lipoprotein ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have clinical in predicting the prognosis of acute ischaemic stroke (AIS) patients. No studies have compared the predictive value of these six composite inflammatory markers. This study included 516 AIS patients with AIS symptoms for < 24 h. The short-term prognosis of AIS patients at 30 days was assessed using the modified Rankin scale (mRS), an mRS score > 2 defining poor prognosis. The results of the univariate analysis showed that all six composite inflammatory indices, SIRI, SII, NHR, NLR, PLR and MLR, were associated with a poor prognosis in patients with AIS. All six composite inflammatory indicators correlated with the short-term prognosis of AIS patients. The six composite inflammation indicators were included in the binary logistic regression, and the results showed that SIRI, NLR and PLR were found to be independent risk factors for poor short-term prognosis in AIS patients. Among the six inflammatory markers, SIRI, NLR and PLR were the most clinically valuable for predicting the short-term prognosis of patients with AIS. Peripheral blood indices are easy to obtain clinically and can provide important clinical value for early prognosis and treatment adjustment.

Benserazide is neuroprotective and improves functional recovery after experimental ischemic stroke by altering the immune response.

Stroke is a leading cause of permanent disability worldwide. Despite intensive research over the last decades, key anti-inflammatory strategies that have proven beneficial in pre-clinical animal models have often failed in translation. The importance of neutrophils as pro- and anti-inflammatory peripheral immune cells has often been overlooked in ischemic stroke. However, neutrophils rapidly infiltrate into the brain parenchyma after stroke and secrete an array of pro-inflammatory factors including reactive oxygen species, proteases, cytokines, and chemokines exacerbating damage. In this study, we demonstrate the neuroprotective and anti-inflammatory effect of benserazide, a clinically used DOPA decarboxylase inhibitor, using both in vitro models of inflammation and in vivo mouse models of focal cerebral ischemia. Benserazide significantly attenuated PMA-induced NETosis in isolated human neutrophils. Furthermore, benserazide was able to protect both SH-SY5Y and iPSC-derived human cortical neurons when challenged with activated neutrophils demonstrating the clinical relevance of this study. Additional in vitro data suggest the ability of benserazide to polarize macrophages towards M2-phenotypes following LPS stimulation. Neuroprotective effects of benserazide are further demonstrated by in vivo studies where peripheral administration of benserazide significantly attenuated neutrophil infiltration into the brain, altered microglia/macrophage phenotypes, and improved the behavioral outcome post-stroke. Overall, our data suggest that benserazide could serve as a drug candidate for the treatment of ischemic stroke. The importance of our results for future clinical trials is further underlined as benserazide has been approved by the European Medicines Agency as a safe and effective treatment in Parkinson's disease when combined with levodopa.

S100A9 deletion in microglia/macrophages ameliorates brain injury through the STAT6/PPARγ pathway in ischemic stroke.

BACKGROUND: Microglia and infiltrated macrophages (M/M) are integral components of the innate immune system that play a critical role in facilitating brain repair after ischemic stroke (IS) by clearing cell debris. Novel therapeutic strategies for IS therapy involve modulating M/M phenotype shifting. This study aims to elucidate the pivotal role of S100A9 in M/M and its downstream STAT6/PPARγ signaling pathway in neuroinflammation and phagocytosis after IS. METHODS: In the clinical study, we initially detected the expression pattern of S100A9 in monocytes from patients with acute IS and investigated its association with the long-term prognosis. In the in vivo study, we generated the S100A9 conditional knockout (CKO) mice and compared the stroke outcomes with the control group. We further tested the S100A9-specific inhibitor paqunimod (PQD), for its pharmaceutical effects on stroke outcomes. Transcriptomics and in vitro studies were adopted to explore the mechanism of S100A9 in modulating the M/M phenotype, which involves the regulation of the STAT6/PPARγ signaling pathway. RESULTS: S100A9 was predominantly expressed in classical monocytes and was correlated with unfavorable outcomes in patients of IS. S100A9 CKO mitigated infarction volume and white matter injury, enhanced cerebral blood flow and functional recovery, and prompted anti-inflammation phenotype and efferocytosis after tMCAO. The STAT6/PPARγ pathway, an essential signaling cascade involved in immune response and inflammation, might be the downstream target mediated by S100A9 deletion, as evidenced by the STAT6 phosphorylation inhibitor AS1517499 abolishing the beneficial effect of S100A9 inhibition in tMCAO mice and cell lines. Moreover, S100A9 inhibition by PQD treatment protected against neuronal death in vitro and brain injuries in vivo. CONCLUSION: This study provides evidence for the first time that S100A9 in classical monocytes could potentially be a biomarker for predicting IS prognosis and reveals a novel therapeutic strategy for IS. By demonstrating that S100A9-mediated M/M polarization and phagocytosis can be reversed by S100A9 inhibition in a STAT6/PPARγ pathway-dependent manner, this study opens up new avenues for drug development in the field.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Association of Genetically Predicted Anxiety and Depression With Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: Anxiety and depression have implications for ischemic stroke recovery. This study explored the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke using Mendelian randomization (MR) approach. METHODS: Independent genetic variants associated with anxiety and depression at genome-wide significance level (p < 5 × 10-8) were obtained from large-scale genome-wide association studies (Nmax = 1,306,354). Genetic results of poststroke outcome were obtained from Genetics of Ischemic Stroke Functional Outcome meta-analysis (N = 6,021). Three months after ischemic stroke event, the functional outcome was appraised with the modified Rankin Scale (mRS) score, and a mRS >2 was defined as worse functional outcome. Odds ratios (ORs) and 95% CIs are reported for the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke. The inverse-variance weighted method was adopted to pool estimates. Alternative MR methods such as the weighted median and MR using the Robust Adjusted Profile Score were used as sensitivity analyses. The intercept of MR-Egger regression was also adopted to assess pleiotropy. The heterogeneity among variants was assessed by I2 and Q statistics. RESULTS: Genetic liability to depression was associated with worse functional outcome after stroke (mRS 3-6, OR 2.30; 95% CI 1.18-4.49, p = 0.015). Sensitivity analyses produced consistent results. The bidirectional MR analysis indicates that poststroke outcome did not influence liability to depression (OR 1.01, 95% CI 0.99-1.03; p = 0.436). By comparison, genetic liability to anxiety was not related with poststroke outcome (OR 1.03; 95% CI 0.71-1.50; p = 0.869). Analyses in models without adjustment for stroke severity also indicated that genetic liability to depression was related with poor functional outcome after ischemic stroke (OR 2.54; 95% CI 1.41-4.58; p = 0.002). No evidence of heterogeneity or directional pleiotropy was observed (p > 0.05). DISCUSSION: Our MR study provides evidence to support detrimental effects of depression on ischemic stroke functional outcome. Future studies are warranted to explore whether clinical intervention on depression can ameliorate functional outcome after ischemic stroke.

High prevalence of intracranial arterial stenosis among acute ischemic stroke patients in a Brazilian center: a transcranial color-coded duplex sonography study.

BACKGROUND: There is limited data available regarding the prevalence of intracranial arterial stenosis (ICAS) among acute ischemic stroke (AIS) patients in Brazil and Latin America. OBJECTIVE: The present study sought to investigate the frequency and predictors of ICAS among patients with AIS or transient ischemic attack (TIA) in a Brazilian center, with transcranial color-coded duplex sonography (TCCS) technique. METHODS: Consecutive AIS and TIA patients, admitted to an academic public comprehensive stroke center in Brazil from February to December 2014, evaluated by TCCS were prospectively selected. Vascular narrowings > 50% were considered as ICAS, based on ultrasound criteria previously defined in the literature. RESULTS: We assessed 170 consecutive patients with AIS or TIA, of whom 27 (15.9%) were excluded due to an inadequate transtemporal acoustic bone window. We confirmed ICAS in 55 patients (38.5%). The most common location was the proximal segment of the middle cerebral artery (28.2%), followed by the vertebral (15.4%), posterior cerebral (13.6%), terminal internal carotid (9.1%) and basilar (8.2%) arteries. On multivariate models adjusting for potential confounders, systolic blood pressure (OR: 1.03, 95%CI: 1.01-1.04; p = 0.008) was independently associated with ICAS. CONCLUSION: We found significant ICAS in approximately ⅓ of patients admitted with symptoms of AIS or TIA in a public tertiary academic stroke center in Brazil. The TCCS is an accessible and noninvasive technique that can be used to investigate the presence of moderate and severe ICAS, especially in patients who cannot be exposed to more invasive exams, such as the use of intravenous contrast agents.

ANTECEDENTES: Dados acerca da prevalência da estenose arterial intracraniana (EAIC) entre os pacientes com acidente vascular isquêmico (AVCi) agudo no Brasil e América Latina são limitados. OBJETIVO: O presente estudo pretendeu investigar a frequência e os preditores da EAIC nos pacientes AVCi ou ataque isquêmico transitório (AIT) em um centro brasileiro utilizando o Doppler transcraniano colorido (duplex transcraniano). MéTODOS: Pacientes consecutivos com AVCi ou AIT, admitidos entre fevereiro e dezembro de 2014 em um centro acadêmico brasileiro especializado em doenças cerebrovasculares, foram avaliados prospectivamente com duplex transcraniano. Os estreitamentos vasculares > 50% foram considerados como EAIC, baseado em critérios ultrassonográficos definidos previamente na literatura. RESULTADOS: Foram avaliados 170 pacientes com AVCi ou AIT, dos quais 27 (15,9%) foram excluídos em decorrência da janela óssea transtemporal acústica inadequada. Confirmamos EAIC em 55 pacientes (38,5%). A localização mais comum foi o segmento proximal da artéria cerebral média (28,2%), seguida pelas artérias vertebral (15,4%), cerebral posterior (13,6%), carótida interna terminal (9,1%) e basilar (8,2%). No modelo multivariado, ajustado para os potenciais confundidores, a pressão arterial sistólica aumentada (OR: 1,03; IC 95%: 1,01­1,04; p = 0,008) foi independentemente associada a EAIC. CONCLUSãO: Foi identificada EAIC significativa em quase ⅓ dos pacientes admitidos com sintomas de AVCi ou AIT em um serviço acadêmico público de atendimento especializado em doenças cerebrovasculares. O Doppler transcraniano colorido é uma ferramenta acessível e não invasiva que pode ser utilizada com segurança para a investigação da presença de EAIC moderada ou grave, especialmente nos pacientes que não podem ser expostos a exames complementares mais invasivos com uso de contraste intravenoso.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol.

INTRODUCTION: Poststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality at 3 months. This study aims to evaluate the association between glucose levels during cerebral reperfusion with MT and functional recovery at 3 months, measured by subcutaneous continuous glucose monitoring (CGM) devices. METHODS: This prospective observational study aims to recruit 100 patients with ischaemic stroke and large anterior circulation vessel occlusion, in whom MT is indicated. CGM will be performed using a Freestyle Libre ProIQ device (FSL-CGM, Abbott Diabetes Care, Alameda, California, USA), which will be implanted on admission to the emergency department, to monitor glucose levels before, during and after reperfusion. The study's primary endpoint will be the functional status at 3 months, as measured by the dichotomised modified Rankin Scale (0-2 indicating good recovery and 3-6 indicating dependency or death). We will analyse expression profiles of microRNA (miRNA) at the time of reperfusion and 24 hours later, as potential biomarkers of ischaemic-reperfusion injury. The most promising miRNAs include miR-100, miR-29b, miR-339, miR-15a and miR-424. All patients will undergo treatment according to current international recommendations and local protocols for the treatment of stroke, including intravenous thrombolysis if indicated. ETHICS AND DISSEMINATION: This study (protocol V.1.1, dated 29 October 2021, code 6017) has been approved by the Clinical Research Ethics Committee of La Paz University Hospital (Madrid, Spain) and has been registered in ClinicalTrials.gov (NCT05871502). Study results will be disseminated through peer-reviewed publications in Open Access format and at conference presentations. TRIAL REGISTRATION NUMBER: NCT05871502.

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Age and Functional Outcomes in Patients With Large Ischemic Stroke Receiving Endovascular Thrombectomy.

Importance: Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials. Objective: To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct. Design, Setting, and Participants: This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes. Exposure: Age. Main Outcomes and Measures: Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6). Results: A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27). Conclusions and Relevance: In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

Genetically predicted small dense low-density lipoprotein cholesterol and ischemic stroke subtype: multivariable Mendelian randomization study.

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002). Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.

Association between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

INTRODUCTION: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. METHODS: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. RESULTS: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). CONCLUSION: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Application and Development of Cell Membrane Functionalized Biomimetic Nanoparticles in the Treatment of Acute Ischemic Stroke.

Ischemic stroke is a serious neurological disease involving multiple complex physiological processes, including vascular obstruction, brain tissue ischemia, impaired energy metabolism, cell death, impaired ion pump function, and inflammatory response. In recent years, there has been significant interest in cell membrane-functionalized biomimetic nanoparticles as a novel therapeutic approach. This review comprehensively explores the mechanisms and importance of using these nanoparticles to treat acute ischemic stroke with a special emphasis on their potential for actively targeting therapies through cell membranes. We provide an overview of the pathophysiology of ischemic stroke and present advances in the study of biomimetic nanoparticles, emphasizing their potential for drug delivery and precision-targeted therapy. This paper focuses on bio-nanoparticles encapsulated in bionic cell membranes to target ischemic stroke treatment. It highlights the mechanism of action and research progress regarding different types of cell membrane-functionalized bi-onic nanoparticles such as erythrocytes, neutrophils, platelets, exosomes, macrophages, and neural stem cells in treating ischemic stroke while emphasizing their potential to improve brain tissue's ischemic state and attenuate neurological damage and dysfunction. Through an in-depth exploration of the potential benefits provided by cell membrane-functionalized biomimetic nanoparticles to improve brain tissue's ischemic state while reducing neurological injury and dysfunction, this study also provides comprehensive research on neural stem cells' potential along with that of cell membrane-functionalized biomimetic nanoparticles to ameliorate neurological injury and dysfunction. However, it is undeniable that there are still some challenges and limitations in terms of biocompatibility, safety, and practical applications for clinical translation.