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BACKGROUND: Mechanical thrombectomy (MT) has become the gold standard care for treating acute ischemic stroke (AIS) due to large vessel occlusion. Emerging evidence suggests that understanding the composition of clots prior to intervention could be useful for the selection of neuroendovascular techniques, potentially improving the efficacy of treatments. However, current imaging modalities lack the ability to distinguish clot composition accurately and reliably. Since water content can influence signal intensity on CT and MRI scans, its assessment may provide indirect clues about clot composition. This study aimed to elucidate the correlation between water content and clot composition using human clots retrieved from stroke patients and experimentally generated ovine clots. MATERIALS AND METHODS: This study involved an analysis of ten clots retrieved from patients with AIS undergoing MT. Additionally, we created ten red blood cells (RBC)-rich and ten fibrin-rich ovine blood clots, which were placed in a human intracranial vascular model under realistic flow conditions. The water content and compositions of these clots were evaluated, and linear regression analyses were performed to determine the relationship between clot composition and water content. RESULTS: The regression analysis in human stroke clots revealed a significant negative association between RBC concentration and water content. We also observed a positive correlation between water content and both fibrin and platelets in ovine blood clots. Conclusion.

Background: Clinical observations have shown that many patients with ischemic stroke (IS) have a history of obstructive sleep apnea (OSA) both before and after the stroke's onset, suggesting potential underlying connections and shared comorbid mechanisms between the two conditions. The aim of this study is to identify the genetic characteristics of OSA patients who develop IS and to establish a reliable disease diagnostic model to assess the risk of IS in OSA patients. Methods: We selected IS and OSA datasets from the Gene Expression Omnibus (GEO) database as training sets. Core genes were identified using the Limma package, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning algorithms. Gene Set Variation Analysis (GSVA) was conducted for pathway enrichment analysis, while single-sample gene set enrichment analysis (ssGSEA) was employed for immune infiltration analysis. Finally, a diagnostic model was developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, with its diagnostic efficacy validated using receiver operating characteristic (ROC) curves across two independent validation sets. Results: The results revealed that differential analysis and machine learning identified two common genes, TM9SF2 and CCL8, shared between IS and OSA. Additionally, seven signaling pathways were found to be commonly upregulated in both conditions. Immune infiltration analysis demonstrated a significant decrease in monocyte levels, with TM9SF2 showing a negative correlation and CCL8 showing a positive correlation with monocytes. The diagnostic model we developed exhibited excellent predictive value in the validation set. Conclusions: In summary, two immune-related core genes, TM9SF2 and CCL8, were identified as common to both IS and OSA. The diagnostic model developed based on these genes may be used to predict the risk of IS in OSA patients. [ABSTRACT FROM AUTHOR]

Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of immune cells is implicated in the development and progression of numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Monocytes and monocyte-derived macrophages, being important players in the inflammatory response, significantly influence the aging process and the associated increase in inflammatory disease risk. Ischemic stroke is among age-related diseases where inflammation, particularly monocyte-derived macrophages, plays an important deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences the incidence, presentation, and outcomes of ischemic stroke, reflecting both biological differences between men and women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of genes implicated in stroke-related inflammation and post-stroke tissue regeneration depends on age and sex. A flow cytometry analysis of blood samples from 44 healthy volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of NK-cells increased in females. The proportion of B-cells decreased in both sexes with age. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly, ANXA1 and CD36 showed a consistent increase with aging in all monocytes, specifically in intermediate (CD36) and intermediate and non-classical (ANXA1) subtypes. Other genes (IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91) were differentially changed in monocyte subtypes with increasing age. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to explore neurovascular imaging patterns in patients with SARS-CoV-2-related AIS. Methods: We retrospectively analyzed clinical and radiological data of patients hospitalized with AIS and a positive PCR test for SARS-CoV-2 prior to AIS onset. The control group comprised of AIS patients from a pre-COVID-19 pandemic period matched for gender and age. Results: Thirty-five SARS-CoV-2-related stroke patients, and 35 controls were included. Fifty-seven percent of SARS-CoV-2 patients had either mild or asymptomatic disease. A distinctive imaging pattern of floating arterial mural thrombus was detected in 5 patients of the SARS-CoV-2 group. In 4 patients thrombus was attached to a stenotic atherosclerotic plaque in the proximal internal carotid artery. In the 5th patient a cardiac CTA showed multiple floating thrombi in the descending aorta. In the control group, floating thrombus was only detected in one patient. Treatment with dual antiplatelet therapy was associated with thrombus dissolution and good clinical outcome. Patients with floating thrombi had a longer time from SARS-CoV-2 diagnosis to stroke onset (mean 7.4 versus 3.4 days). Conclusions: Floating arterial mural thrombi attached to atherosclerotic plaques are unique characteristic source of AIS in SARS-CoV-2 patients. They may lead to ischemic stroke in patients with mild or asymptomatic infection up to 1–2 weeks from SARS-CoV-2 diagnosis. Patients with embolic AIS and SARS-CoV-2 diagnosis should perform high resolution cranio-cervical vascular imaging to evaluate floating thrombi as a potential embolic source. [ABSTRACT FROM AUTHOR]

Background and purpose: Stroke can lead to significant after-effects, including motor function impairments, language impairments (aphasia), disorders of consciousness (DoC), and cognitive deficits. Computer-aided analysis of EEG connectivity matrices and microstates from bedside EEG monitoring can replace traditional clinical observation methods, offering an automatic approach to monitoring the progression of these after-effects. This EEG-based method also enables quicker and more efficient assessments for medical practitioners. Methods: In this study, we employed Functional Connectivity features that extract spatial representation and Microstate features that focus on the time domain representation to monitor the after-effects of ischemic stroke patients. As the dataset from stroke patients is heavily imbalanced across various clinical after-effects conditions, we designed an ensemble classifier, RSBagging, to address the issue of classifiers often favoring the majority classes in the classification of imbalanced datasets. Results: The experimental results demonstrate that different connectivity matrices are effective for three classification tasks: consciousness level, motor disturbance, and stroke location. Using our RSBagging model, all three tasks achieve over 98% accuracy, sensitivity, specificity, and F1-score, significantly outperforming the existing classifiers SVM, XGBoost, and Random Forest. Conclusion: Therefore, the RSBagging classifier based on connectivity matrices offers an effective method for monitoring the after-effects in stroke patients. [ABSTRACT FROM AUTHOR]

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal treatment of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose or single dose of EVs. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work at the tested dose and frequency, and that a single cumulative dose of EVs further improves the neurological function recovered during handling. These results show the importance of rehabilitation in combination with other treatments such as EVs, and highlight how extensive behavioral testing might influence functional recovery after stroke. [ABSTRACT FROM AUTHOR]

Introduction: In patients suspected of stroke or transient ischemic attack (TIA), rapid triaging is imperative to improve clinical outcomes. For this purpose, balance-eye-face-arm-speech-time (BEFAST) items are used in out-of-hours primary care (OHS-PC). We explored the risk of stroke and TIA among BEFAST positive patients calling to the OHS-PC, and assessed whether additional predictors could improve risk stratification. Methods: This is a cross-sectional study of retrospectively gathered routine care data from telephone triage tape-recordings of patients calling the OHS-PC with neurological deficit symptoms, classified as BEFAST positive. Four models–with the predictors age, sex, a history of cardiovascular or cerebrovascular disease, and cardiovascular risk factors–were fitted using logistic regression to predict the outcome stroke or TIA. Likelihood ratio testing was used to select the best model, which was subsequently internally validated. Results: The risk of stroke or TIA diagnosis was 52% among 1,289 BEFAST positive patients, median age 72 years, 56% female sex. Of patients with the outcome stroke/TIA, 24% received a low urgency allocation, while 92% had signs or symptoms when calling. Only the addition of age and sex improved predicting stroke or TIA (internally validated c-statistic 0.72, 95%CI 0.69–0.75). The predicted risk of stroke or TIA remained below 20% in those aged below 40. Females aged 70 or over and males aged 55 or over, had a predicted risk above 50%. Discussion: Urgency allocation appears to be suboptimal in BEFAST positive patients calling the OHS-PC. Risk stratification could be improved in this setting by adding age and sex. [ABSTRACT FROM AUTHOR]

The prevalence and predictors of mortality following an ischemic stroke or intracerebral hemorrhage have not been well established among patients in Vietnam. 2885 consecutive diagnosed patients with ischemic stroke and intracerebral hemorrhage at ten stroke centres across Vietnam were involved in this prospective study. Posthoc analyses were performed in 2209 subjects (age was 65.4 ± 13.7 years, with 61.4% being male) to explore the clinical characteristics and prognostic factors associated with 90-day mortality following treatment. An explainable machine learning model using extreme gradient boosting and SHapley Additive exPlanations revealed the correlation between original clinical research and advanced machine learning methods in stroke care. In the 90 days following treatment, the mortality rate for ischemic stroke was 8.2%, while for intracerebral hemorrhage, it was higher at 20.5%. Atrial fibrillation was an elevated risk of 90-day mortality in the ischemic stroke patient (OR 3.09; 95% CI 1.90–5.02, p<0.001). Among patients with intracerebral hemorrhage, there was no statistical significance in those with hypertension compared to their counterparts without hypertension (OR 0.65, 95% CI 0.41–1.03, p > 0.05). The baseline NIHSS score was a significant predictor of 90-day mortality in both patient groups. The machine learning model can predict a 0.91 accuracy prediction of death rate after 90 days. Age and NIHSS score were in the top high risks with other features, such as consciousness, heart rate, and white blood cells. Stroke severity, as measured by the NIHSS, was identified as a predictor of mortality at discharge and the 90-day mark in both patient groups. [ABSTRACT FROM AUTHOR]

Objective: To explore whether miR-199a-5p regulated BBB integrity through PI3K/Akt pathway after ischemia stroke. Methods: Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion(MCAO) were used in experiment. The Ludmila Belayev 12-point scoring was used to measure the neurological function of MCAO rats. The Evans Blue Stain, immunofluorescence staining, western-blotting and RT-PCR were performed to evaluate the effects of miR-199a-5p mimic on BBB integrity in rats following MCAO. Results: The result suggested that miR-199a-5p mimic treatment possessed the potential to boost proprioception and motor activity of MCAO rats. MiR-199a-5p decreased the expression of PIK3R2 after MCAO, activated Akt signaling pathway, and increased the expression of Claudin-5 and VEGF in the ischemic penumbra. Furthermore, miR-199a-5p alleviated inflammation after cerebral ischemia. BBB leakage and neurocyte apoptosis were cut down in MCAO rats treated with miR-199a-5p mimic. Conclusions: MiR-199a-5p mimic decreased the expression of PIK3R2 and activated Akt signaling pathway after ischemia stroke, reduced the expression of inflammatory cytokines, and attenuated BBB disruption after ischemic stroke. [ABSTRACT FROM AUTHOR]

Motivation: The association between weather conditions and stroke incidence has been a subject of interest for several years, yet the findings from various studies remain inconsistent. Additionally, predictive modelling in this context has been infrequent. This study explores the relationship of extremely high ischaemic stroke incidence and meteorological factors within the Slovak population. Furthermore, it aims to construct forecasting models of extremely high number of strokes. Methods: Over a five-year period, a total of 52,036 cases of ischemic stroke were documented. Days exhibiting a notable surge in ischemic stroke occurrences (surpassing the 90th percentile of historical records) were identified as extreme cases. These cases were then scrutinized alongside daily meteorological parameters spanning from 2015 to 2019. To create forecasts for the occurrence of these extreme cases one day in advance, three distinct methods were employed: Logistic regression, Random Forest for Time Series, and Croston's method. Results: For each of the analyzed stroke centers, the cross-correlations between instances of extremely high stroke numbers and meteorological factors yielded negligible results. Predictive performance achieved by forecasts generated through multivariate logistic regression and Random Forest for time series analysis, which incorporated meteorological data, was on par with that of Croston's method. Notably, Croston's method relies solely on the stroke time series data. All three forecasting methods exhibited limited predictive accuracy. Conclusions: The task of predicting days characterized by an exceptionally high number of strokes proved to be challenging across all three explored methods. The inclusion of meteorological parameters did not yield substantive improvements in forecasting accuracy. [ABSTRACT FROM AUTHOR]

To counter the spread of COVID-19, the French government imposed several stringent social and political measures across its entire population. We hereto assess the impact of these political decisions on healthcare access in 2020, focusing on patients who suffered from an ischemic stroke. We divide our analysis into four distinct periods: the pre-COVID-19 pandemic period, the lockdown period, the "in-between" or transitional period, and the shutdown period. Our methodology involves utilizing a retrospective dataset spanning 2019–2020, an exhaustive French national hospital discharge diagnosis database for stroke inpatients, integrated with income information from the reference year of 2019. The results reveal that the most affluent were more likely to forgo medical care, particularly in heavily affected areas. Moreover, the most disadvantaged exhibited even greater reluctance to seek care, especially in the most severely impacted regions. The data suggest a loss of opportunity for less severely affected patients to benefit from healthcares during this lockdown period, regardless of demographic, location, and socioeconomic determinants. Furthermore, our analysis reveals a notable discrepancy in healthcare-seeking behavior, with less affluent patients and seniors (over 75 years old) experiencing slower rates of return to healthcare access compared to pre-pandemic levels. This highlights a persistent gap in healthcare accessibility, particularly among socioeconomically disadvantaged groups, despite the easing of COVID-19 restrictions. [ABSTRACT FROM AUTHOR]

Sustained compressive injury (SCI) in the brain is observed in numerous injury and pathological scenarios, including tumors, ischemic stroke, and traumatic brain injury-related tissue swelling. Sustained compressive injury is characterized by tissue loading over time, and currently, there are few in vitro models suitable to study neural cell responses to strain-dependent sustained compressive injury. Here, we present an in vitro model of sustained compressive neural injury via centrifugation. Spheroids were made from neonatal rat cortical cells seeded at 4000 cells/spheroid and cultured for 14 days in vitro. A subset of spheroids was centrifuged at 104, 209, 313 or 419 rads/s for 2 minutes. Modeling the physical deformation of the spheroids via finite element analyses, we found that spheroids centrifuged at the aforementioned angular velocities experienced pressures of 10, 38, 84 and 149 kPa, respectively, and compressive (resp. tensile) strains of 10% (5%), 18% (9%), 27% (14%) and 35% (18%), respectively. Quantification of LIVE-DEAD assay and Hoechst 33342 nuclear staining showed that centrifuged spheroids subjected to pressures above 10 kPa exhibited significantly higher DNA damage than control spheroids at 2, 8, and 24 hours post-injury. Immunohistochemistry of β3-tubulin networks at 2, 8, and 24 hours post-centrifugation injury showed increasing degradation of microtubules over time with increasing strain. Our findings show that cellular injuries occur as a result of specific levels and timings of sustained tissue strains. This experimental SCI model provides a high throughput in vitro platform to examine cellular injury, to gain insights into brain injury that could be targeted with therapeutic strategies. [ABSTRACT FROM AUTHOR]

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86–0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79–0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07–1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS. [ABSTRACT FROM AUTHOR]

Introduction: Stroke is the second leading cause of death in Europe. In the case of stroke survival (almost 70%), only 25% of patients recover completely, while the remaining 75% will undergo a rehabilitation phase that varying from months to years. The primary outcomes of a stroke involve motor impairment in the upper limbs, resulting in a partial or complete inability to move the limb on the right or left side, depending on the affected hemisphere. Furthermore, the motor deficit distorts the proprioception of the body and the embodiment ability of the injured limb. This could be rehabilitated through the paradigm of body illusion that modulates the motor rehabilitation. The present protocol aims to investigate the effectiveness of a Virtual Reality system for sensorimotor and proprioception upper limb deficit compared to a traditional upper limb rehabilitation program. Method: This study has a randomized and controlled design with control and experimental groups, and 4 measurement times: pre-intervention, immediately after the intervention, and two follow-ups (at 6 and 12 months). The inclusion criteria are: (a) Being 18 to 85 years old, both males and females; (b) Suffering from ischemic or haemorrhagic stroke; (c) The stroke event must have occurred from two to eighteen months before recruitment; (d) Patients must have moderate to severe upper limb motor deficit, and the alteration of sensorimotor and proprioception abilities of the injury upper limb; (e) Patients must understand and sign the written consent for enrolment. The rehabilitation last four weeks with three sessions per week at Bellaria Hospital of Bologna (Italy). The VR protocol uses two types of technology: immersive and non-immersive, and the control group follow the traditional rehabilitation program. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to investigate the health literacy level and influencing factors of patients with ischemic stroke. Design: A cross-sectional study was conducted. Methods: We used convenient sampling to recruit potential participants. Patients with ischemic stroke who were hospitalized in the Department of Neurology, West China Hospital, Sichuan University in China from January 2022 to May 2023 were selected as subjects to complete the questionnaire survey. We used the National Institute of Health Stroke Scale to assess the neurological impairment of patients and the Health Literacy Scale for Chronic Patients to assess the health literacy level of patients. Results: The overall health literacy level of ischemic stroke patients was high (99.13 ± 10.15). Age, education level, per capita monthly family income, living situations and National Institutes of Health Stroke Scale score were independent risk factors affecting the health literacy level of patients with ischemic stroke. Patients with a higher education level (β = 0.151, P = 0.006) and higher per capita monthly family income (β = 0.179, P = 0.001) had higher levels of health literacy. Patients who lived with their spouses (β = -0.117, P = 0.012) had higher health literacy. Patients at an older age (β = -0.151, P = 0.001) and patients with higher NIHSS scores (β = -0.450, P = 0.001) had lower health literacy levels. Conclusions: Age, education level, family per capita monthly income, living situations and National Institute of Health Stroke Scale score were related to the health literacy level of patients with ischemic stroke. According to these associated factors, targeted health education should be developed to improve the health literacy of patients and health outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Over the last decade, there have been significant advances in treatments for anterior ischemic stroke, most notably endovascular thrombectomy (EVT). Despite the success of EVT on overall outcomes, intracerebral hemorrhage (ICH) is an important post-procedure complication, often associated with mortality and disability. Hence, predicting the risk of ICH can inform EVT decision making. The ASPECT score is used globally to predict patients' prognosis post-reperfusion therapy. Our objective is to perform a systematic review to collect and synthesize data on the association between ASPECT scores on CT, CTP and DWI-MRI (CT-ASPECT, CTP-ASPECT, and DWI-ASPECT) and the risk of symptomatic ICH after EVT for anterior circulation strokes. Methods and analysis: We will conduct a broad search of various electronic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and the Cochrane Database of Systematic Reviews) to identify studies published after January 1st, 2012 (commonly accepted as the beginning of the modern EVT era based on availability of stent-retrievers). Two independent reviewers will screen and include studies evaluating associations between symptomatic ICH after thrombectomy and baseline CT-ASPECT, CTP-ASPECT and DWI-ASPECT scores. Data will be extracted to quantify the risk of sICH after EVT based on the ASPECT scoring. Trial registration: PROSPERO registration number:CRD42023459860. [ABSTRACT FROM AUTHOR]

Background and purpose: Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. Methods: Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. Results: Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. Conclusions: Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) is a significant global health issue, directly impacting mortality and disability. The Totaled Health Risks in Vascular Events (THRIVE) score is appreciated for its simplicity and ease of use to predict stroke clinical outcomes; however, it lacks laboratory and neuroimaging data, which limits its ability to predict outcomes precisely. Our study evaluates the impact of integrating the 24-hour Alberta Stroke Program Early CT Score (ASPECTS) and hemoglobin-to-red cell distribution width (HB/RDW) ratio into the THRIVE score using the multivariable fractional polynomial (MFP) method (combined THRIVE-MFP model) compared to the THRIVE-c model. We aim to assess their added value in predicting in-hospital mortality (IHM) prognosis. Materials and methods: A retrospective study from January 2015 to July 2022 examined consecutive AIS patients receiving intravenous thrombolysis. Data on THRIVE scores, 24-hour ASPECTS, and HB/RDW levels were collected upon admission. The model was constructed using logistic regression and the MFP method. The prognostic value was determined using the area under the receiver operating characteristic curve (AuROC). Ischemic cerebral lesions within the middle cerebral artery territory were evaluated with non-contrast computed tomography (NCCT) after completing 24 hours of intravenous thrombolysis (24-hour ASPECTS). Results: Among a cohort of 345 patients diagnosed with AIS who received intravenous thrombolysis, 65 individuals (18.8%) experienced IHM. The combined THRIVE-MFP model was significantly superior to the THRIVE-c model in predicting IHM (AuROC 0.980 vs. 0.876, p<0.001), 3-month mortality (AuROC 0.947 vs. 0.892, p<0.001), and 3-month poor functional outcome (AuROC 0.910 vs. 0.853, p<0.001). Conclusion: The combined THRIVE-MFP model showed excellent predictive performance, enhancing physicians' ability to stratify patient selection for intensive neurological monitoring and guiding treatment decisions. Incorporating 24-hour ASPECTS on NCCT and HB/RDW proved valuable in mortality prediction, particularly for hospitals with limited access to advanced neuroimaging resources. [ABSTRACT FROM AUTHOR]

Inflammation-derived oxidative stress is postulated to contribute to neuronal damage leading to poor clinical outcomes in Acute Ischemic Stroke (AIS). We aimed to investigate the association between serum levels of selected cytokines (IL-1β, IFN-γ, IL-4), and vitamin D in ischemic stroke progression, and their accuracy in predicting AIS prognosis, among Sri Lankans. We compared 60 AIS patients admitted in 4 phases post-stroke onset (<6 h; 6–24 h; 24–48 h; 48–96 h; n = 15/phase), with 15 age- and sex-matched controls. The 30-day functional outcome (FO) was assessed using the modified Rankin Scale (mRS). Serum cytokine and vitamin D levels were quantified using sandwich ELISAs, and competitive ELISA, respectively. The CombiROC web tool established optimal prognostic biomarker combinations. Serum IL-1β and IFN-γ were elevated in all four phases following stroke onset while IL-4 was elevated exclusively in the recovery phase (48–96 h) (p<0.05). Th1 bias polarization of the Th1:Th2 cytokine (IFN-γ:IL-4) ratio occurred with AIS progression while a Th2 bias occurred during AIS recovery (p<0.05). Lower serum IL-1β and higher IL-4 levels were associated with a good FO (p<0.05), while lower Vitamin D levels were related to a poor FO (p = 0.001). The triple-biomarker panel, IL-4- IFN-γ -Vit D, accurately predicted AIS prognosis (sensitivity = 100%, specificity = 91.9%, area under the curve = 0.98). Serum immunologic mediators IFN-γ, IL-4, and vitamin D may be useful biomarkers of AIS prognosis and may serve as therapeutic targets in improving stroke outcomes. Vitamin D supplementation may improve the prognosis of AIS patients. Furthermore, binary logistic model fitted for FO indicated Th1:Th2 cytokine ratio (IFN-γ:IL-4), vitamin D status, history of stroke, and ischemic heart disease as significant predictors of AIS prognosis. [ABSTRACT FROM AUTHOR]

Stroke patients rarely have satisfactory survival, which worsens further if comorbidities develop in such patients. Limited data availability from Southeast Asian countries, especially Indonesia, has impeded the disentanglement of post-stroke mortality determinants. This study aimed to investigate predictors of in-hospital mortality in patients with ischemic stroke (IS). This retrospective observational study used IS medical records from the National Brain Centre Hospital, Jakarta, Indonesia. A theoretically driven Cox's regression and Fine-Gray models were established by controlling for age and sex to calculate the hazard ratio of each plausible risk factor for predicting in-hospital stroke mortality and addressing competing risks if they existed. This study finally included 3,278 patients with IS, 917 (28%) of whom had cardiovascular disease and 376 (11.5%) suffered renal disease. Bivariate exploratory analysis revealed lower blood levels of triglycerides, low density lipoprotein, and total cholesterol associated with in-hospital-stroke mortality. The average age of patients with post-stroke mortality was 64.06 ± 11.32 years, with a mean body mass index (BMI) of 23.77 kg/m2 and a median Glasgow Coma Scale (GCS) score of 12 and an IQR of 5. Cardiovascular disease was significantly associated with IS mortality risk. NIHSS score at admission (hazard ratio [HR] = 1.04; 95% confidence interval [CI]: 1.00–1.07), male sex (HR = 1.51[1.01–2.26] and uric acid level (HR = 1.02 [1.00–1.03]) predicted survivability. Comorbidities, such as cardiovascular disease (HR = 2.16 [1.37–3.40], pneumonia (HR = 2.43 [1.42–4.15] and sepsis (HR = 2.07 [1.09–3.94, had higher hazards for post-stroke mortality. Contrarily, the factors contributing to a lower hazard of mortality were BMI (HR = 0.94 [0.89–0.99]) and GCS (HReye = 0.66 [0.48–0.89]. In summary, our study reported that male sex, NIHSS, uric acid level, cardiovascular diseases, pneumonia, sepsis. BMI, and GCS on admission were strong determinants of in-hospital mortality in patients with IS. [ABSTRACT FROM AUTHOR]

Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment. [ABSTRACT FROM AUTHOR]

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox proportional hazards models were used to test the association between each PRS and ASCVD, adjusting for traditional risk factors, ankle-brachial index, carotid intima media thickness, and carotid plaque. The hazard ratios (HR) for the CHD and IS PRS were significant with HR of 1.50 (95% CI: 1.36-1.66) and 1.31 (95% CI: 1.18-1.45) respectively for the risk of incident ASCVD per standard deviation increase in CHD and IS PRS among White participants after adjusting for traditional risk factors. The HR for the CHD PRS was not significant with an HR of 0.95 (95% CI: 0.79-1.13) for the risk of incident ASCVD in Black participants. The HR for the IS PRS was significant with an HR of 1.26 (95%CI: 1.05-1.51) for the risk of incident ASCVD in Black participants. The association of the CHD and IS PRS with ASCVD was not attenuated in White participants after adjustment for ankle-brachial index, carotid intima media thickness, and carotid plaque. The CHD and IS PRS do not cross-predict well, and predict better the outcome for which they were created than the composite ASCVD outcome. Thus, the use of the composite outcome of ASCVD may not be ideal for genetic risk prediction.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007–2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57–0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77–0.78) and ICH models (0.77, 95%CI 0.75–0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data. [ABSTRACT FROM AUTHOR]

Background: Osteoprotegerin (OPG) is supposed to participate in the development of atherosclerosis and cardio-cerebrovascular disease. However, the results of research on relationship between OPG and ischemic stroke (IS) are controversial. Therefore, we carried out the first systematic review and meta-analysis to evaluate prognostic effect of osteoprotegerin in patients with IS. Methods: We comprehensively searched databases of PubMed, Embase, and the Cochrane Library through 21 August 2023 to identify observational studies that evaluated effect of OPG on poor functional outcome (modified Rankin Scale [mRS] Score of 3–6) and mortality in patients with IS. Adjusted odds ratios (aOR) with a 95% confidence interval (CI) of each included study were used as much as possible to assess the pooled effect. Results: Five studies that enrolled 4,506 patients in total fulfilled our inclusion criteria. Three studies were included in the pooled analysis for each endpoint since one of the included studies had provided data on poor functional outcome as well as mortality. OPG was neither associated with poor functional outcome (aOR 1.29, 95% CI 0.90–1.85) nor with mortality (aOR 1.57, 95% CI 0.90–2.74) in patients with IS. Conclusions: There is insufficient evidence to demonstrate the correlation between OPG and mortality or poor functional outcome in IS patients. OPG cannot be applied to predict worse neurological function in IS patients based on the current evidence. [ABSTRACT FROM AUTHOR]

Ischemic stroke causes a lack of oxygen and glucose supply to brain, eventually leads to severe neurological disorders. Retinoic acid is a major metabolic product of vitamin A and has various biological effects. The PI3K-Akt signaling pathway is an important survival pathway in brain. Phosphorylated Akt is important in regulating survival and apoptosis. We examined whether retinoic acid has neuroprotective effects in stroke model by regulating Akt and its downstream protein, Bad. Moreover, we investigated the relationship between retinoic acid and Bcl-2 family protein interactions. Animals were intraperitoneally administered vehicle or retinoic acid (5 mg/kg) for four days before surgery and ischemic stroke was induced by middle cerebral artery occlusion (MCAO) surgery. Neurobehavioral tests were performed 24 h after MCAO and cerebral cortical tissues were collected. Cresyl violet staining and TUNEL histochemistry were performed, Western blot and immunoprecipitation analysis were performed to elucidate the expression of various proteins. Retinoic acid reduced neurological deficits and histopathological changes, decreased the number of TUNEL-positive cells, and alleviated reduction of phospho-PDK1, phospho-Akt, and phospho-Bad expression caused by MCAO damage. Immunoprecipitation analysis showed that MCAO damage reduced the interaction between phospho-Bad and 14-3-3, which was attenuated by retinoic acid. Furthermore, retinoic acid mitigated the increase in Bcl-2/Bad and Bcl-xL/Bad binding levels and the reduction in Bcl-2/Bax and Bcl-xL/Bax binding levels caused by MCAO damage. Retinoic acid alleviated MCAO-induced increase of caspase-3 and cleaved caspase-3 expression. We demonstrate that retinoic acid prevented apoptosis against cerebral ischemia through phosphorylation of Akt and Bad, maintenance of phospho-Bad and 14-3-3 binding, and regulation of Bcl-2 family protein interactions. [ABSTRACT FROM AUTHOR]

Globally, stroke is the third-leading cause of mortality and disability combined, and one of the costliest diseases in society. More accurate predictions of stroke outcomes can guide healthcare organizations in allocating appropriate resources to improve care and reduce both the economic and social burden of the disease. We aim to develop and evaluate the performance and explainability of three supervised machine learning models and the traditional multinomial logistic regression (mLR) in predicting functional dependence and death three months after stroke, using routinely-collected data. This prognostic study included adult patients, registered in the Swedish Stroke Registry (Riksstroke) from 2015 to 2020. Riksstroke contains information on stroke care and outcomes among patients treated in hospitals in Sweden. Prognostic factors (features) included demographic characteristics, pre-stroke functional status, cardiovascular risk factors, medications, acute care, stroke type, and severity. The outcome was measured using the modified Rankin Scale at three months after stroke (a scale of 0–2 indicates independent, 3–5 dependent, and 6 dead). Outcome prediction models included support vector machines, artificial neural networks (ANN), eXtreme Gradient Boosting (XGBoost), and mLR. The models were trained and evaluated on 75% and 25% of the dataset, respectively. Model predictions were explained using SHAP values. The study included 102,135 patients (85.8% ischemic stroke, 53.3% male, mean age 75.8 years, and median NIHSS of 3). All models demonstrated similar overall accuracy (69%–70%). The ANN and XGBoost models performed significantly better than the mLR in classifying dependence with F1-scores of 0.603 (95% CI; 0.594–0.611) and 0.577 (95% CI; 0.568–0.586), versus 0.544 (95% CI; 0.545–0.563) for the mLR model. The factors that contributed most to the predictions were expectedly similar in the models, based on clinical knowledge. Our ANN and XGBoost models showed a modest improvement in prediction performance and explainability compared to mLR using routinely-collected data. Their improved ability to predict functional dependence may be of particular importance for the planning and organization of acute stroke care and rehabilitation. [ABSTRACT FROM AUTHOR]

Early neurological deterioration (END) is progressive neurological deterioration with an increase in NIHSS score of 2 points or more in the first 72 hours from the onset of acute ischemic stroke. END increases the risk of poor clinical outcomes at day 90 of ischemic stroke. We will study the frequency, predictors, and outcomes of patients with END in a case-control study at a comprehensive stroke centre in Vietnam. of the design is a descriptive observational study, longitudinal follow-up of patients with minor stroke hospitalized at the Stroke Center of Bach Mai Hospital from December 1, 2023, to December 1, 2024. Minor stroke patients characterized by NIHSS score ≤ 5 hospitalized within 24 hours of symptom onset will be recruited. The estimated END rate is about 30%, relative accuracy ε = 0.11, 95% reliability, expected 5% of patients lost data or follow-up, and an estimated sample size of 779 patients. This study will help determine the END rate in patients with minor stroke and related factors, thereby building a prognostic model for END. Our study determined the END rate in patients with minor stroke in Vietnam and also proposed risk factors for minor stroke management and treatment. [ABSTRACT FROM AUTHOR]

Background: As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated. Methods: Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed. Results: At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process. Conclusions: This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke. [ABSTRACT FROM AUTHOR]

Aims: Association between whole blood viscosity (WBV) and an increased risk of cardiovascular disease (CVD) has been reported. However, the causal relationship between WBV and CVD remains not thoroughly investigated. The aim of this study was to investigate the causal relation between WBV and CVD. Methods: Two-sample Mendelian randomization (MR) was employed, with inverse variance weighting (IVW) as the primary method, to investigate the casual relationship between WBV and CVD. The calculated WBV and medical records of 378,210 individuals participating in the UK Biobank study were divided into halves and analyzed. Results: The means of calculated WBVs were 16.9 (standard deviation: 0.8) and 55.1 (standard deviation: 17.2) for high shear rate (HSR) and low shear rate (LSR), respectively. 37,859 (10.0%) major cardiovascular events (MACE) consisted of 23,894 (6.3%) cases of myocardial infarction (MI), 9,245 (2.4%) cases of ischemic stroke, 10,377 (2.7%) cases of revascularization, and 5,703 (1.5%) cases of coronary heart disease-related death. In the MR analysis, no evidence was found indicating a causal effect of WBV on MACE (IVW p-value for HSR = 0.81, IVW p-value for LSR = 0.47), MI (0.92, 0.83), ischemic stroke (0.52, 0.74), revascularization (0.71, 0.54), and coronary heart disease-related death (0.83, 0.70). The lack of sufficient evidence for causality persisted in other MR methods, including weighted median and MR-egger. Conclusions: The Mendelian randomization analysis conducted in this study does not support a causal relationship between calculated WBV and CVD. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022. Methods: This study is a secondary analysis of data from MAAESTRO with a matched nested case-control design and 1:2 ratio. DOAC intake was measured with a small electronic device (Time4MedTM). We defined two arbitrary intervals of 17 days and 95 days as the longest time spans with electronic monitoring data per patient to maximize the number of participants with adequate amount of observation time available for analysis. Taking and timing adherence were calculated retrospectively i.e., prior to the recurrent event for cases. Trendline analysis of adherence over 95 days was calculated. Linear regression analysis was performed after adjusting for the co-variables age and daily pill burden. Sensitivity analysis was performed with controls for intervals in the reverse direction (prospectively). Results: We analyzed 11 cases and 22 matched controls (mean age: 75.9 ± 9.2 years vs. 73.1 ± 8.4 years; n.s.) with similar stroke characteristics (NIHSS, mRS, MoCA) and 36.4% women in each group. Mean adherence values were high and similar between cases and controls (95 days taking: 87.0 ± 18.9% (cases) vs. 90.8 ± 9.8% (controls), n.s.; similar values for timing adherence). Six hemorrhagic and five ischemic events had occurred. Compared to controls, a significantly higher 95 days taking adherence was observed for hemorrhagic events (96.0 ± 5.0% (cases) vs. 88.1 ± 11.5% (controls); p<0.01) and a significantly lower 95 days taking adherence was observed for ischemic events (75.7 ± 24.8% (cases) vs. 94.2 ± 6.2% (controls), p = 0.024). Values for timing adherence were similar. A non-significant downward linear trend of adherence was observed over 95 days independently of the clinical events. The sensitivity analysis showed that the direction of the interval had negligible impact on the 95 days adherence. Conclusion: Because recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC <76%, adherence enhancing interventions seem crucial in anticoagulated AF-patients. However, AF-patients with high adherence might benefit from a regular re-assessment of the bleeding risk as hemorrhagic complications were associated with adherence to DOAC >96%. Trial registration: ClinicalTrials.gov NCT03344146. [ABSTRACT FROM AUTHOR]

Background/aim: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. Materials and methods: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. Results: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. Conclusions: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort. [ABSTRACT FROM AUTHOR]

Aims: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of ischemic strokes annually. Undetected atrial fibrillation (AF) is one important potential underlying cause. For AF, oral anticoagulation has evolved as the most preferable means of secondary stroke prevention. To detect unrecognized paroxysmal AF, long-term ECG monitoring is required, and implantable cardiac monitors (ICM) appear most suitable. Yet, ICMs are particularly costly, implantation is invasive, and remote monitoring places a personnel burden on health care providers. Here, we use data from a large cohort of ESUS patients to systematically analyze the effort of ICM remote monitoring for AF diagnosis and the strain on health care providers. Methods and results: From a prospective, single-center, observational ESUS registry, we analyzed all ICM-equipped patients post-ESUS (n = 172) between January 1st, 2018, and December 31st, 2019. Through January 2nd, 2023, 48 patients (27.9%) were diagnosed with AF by ICM remote monitoring. During follow-up, a total of 29,180 remote monitoring episodes were transmitted, of which 17,742 were alarms for AF. A systematic estimation of workload revealed that on average, 20.3 trained physician workhours are required to diagnose one patient with AF. Conclusion: ICM remote monitoring is useful to diagnose AF in cohort of post-ESUS patients. However, the number of ICM alarms is high, even in a cohort at known high risk of AF and in whom AF detection is therapeutically consequential. Improved automated event classification, clear recommendations for ICM interrogation after AF diagnosis, and a careful patient selection for ICM monitoring are warranted. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular discharge diagnoses may serve as endpoints in epidemiological studies if they have a high validity. Aim was to study if diagnoses-specific characteristics like type, sub-categories, and position of cardiovascular diagnoses affected diagnostic accuracy. Methods: Patients (n = 7,164) with a discharge diagnosis of acute myocardial infarction, heart failure or cerebrovascular disease were included. Data were presented as positive predictive values (PPV) and sensitivity. Results: PPV was high (≥88%) for acute myocardial infarction (n = 2,189) (except for outpatients). For heart failure (n = 4,026) PPV was 67% overall, but higher (>99%) when etiology or echocardiography was included. For hemorrhagic (n = 257) and ischemic (n = 1,034) strokes PPVs were 87% and 80%, respectively, with sensitivity of 79% and 75%. Transient ischemic attacks (n = 926) had PPV 56%, but sensitivity 86%. Primary diagnoses showed higher validity than subsequent diagnoses and inpatient diagnoses were more valid than outpatient diagnoses (except for transient ischemic attack). The diagnoses of acute myocardial infarction and heart failure where most valid when placed at cardiology units, while ischemic stroke when discharged from an internal medicine unit. Conclusions: The diagnoses of acute myocardial infarction and stroke had excellent validity when placed during hospital stays. Similarly, heart failure diagnoses had excellent validity when echocardiography was performed before placing the diagnosis, while overall the diagnoses of heart failure and transient ischemic attack were less valid. In conclusion, the results indicate that cardiovascular diagnoses based on objective findings such as acute myocardial infarction and stroke have excellent validity and may be used as endpoints in clinical epidemiological studies with less rigid validation. [ABSTRACT FROM AUTHOR]

The aim of this study is to define atrial fibrillation (AF) prevalence and incidence rates across minority groups in the United States (US), to aid in diversity enrollment target setting for randomized controlled trials. In AF, US minority groups have lower clinically detected prevalence compared to the non-Hispanic or Latino White (NHW) population. We assess the impact of ascertainment bias on AF prevalence estimates. We analyzed data from adults in Optum's de-identified Clinformatics® Data Mart Database from 2017–2020 in a cohort study. Presence of AF at baseline was identified from inpatient and/or outpatient encounters claims using validated ICD-10-CM diagnosis algorithms. AF incidence and prevalence rates were determined both in the overall population, as well as in a population with a recent stroke event, where monitoring for AF is assumed. Differences in prevalence across cohorts were assessed to determine if ascertainment bias contributes to the variation in AF prevalence across US minority groups. The period prevalence was respectively 4.9%, 3.2%, 2.1% and 5.9% in the Black or African American, Asian, Hispanic or Latino, and NHW population. In patients with recent ischemic stroke, the proportion with AF was 32.2%, 24.3%, 25%, and 24.5%, respectively. The prevalence of AF among the stroke population was approximately 7 to 10 times higher than the prevalence among the overall population for the Asian and Hispanic or Latino population, compared to approximately 5 times higher for NHW patients. The relative AF prevalence difference of the Asian and Hispanic or Latino population with the NHW population narrowed from respectively, -46% and -65%, to -22% and -24%. The study findings align with previous observational studies, revealing lower incidence and prevalence rates of AF in US minority groups. Prevalence estimates of the adult population, when routine clinical practice is assumed, exhibit higher prevalence differences compared to settings in which monitoring for AF is assumed, particularly among Asian and Hispanic or Latino subgroups. [ABSTRACT FROM AUTHOR]

Background: Acupuncture of the governor vessel and Yangming meridian are widely used in the treatment of acute ischemic stroke (AIS). However, the optimal meridian for acupuncture in the treatment of AIS remains uncertain. Purpose: This network meta-analysis study aimed to compare the clinical effectiveness of acupuncture at governor vessel and Yangming meridian in the treatment of AIS. Methods: All relevant studies published in CNKI, WANFANG, VIP, Sinomed, Cochrane Library, Web of Science, Pub Med, and Embase before January 13, 2024 were systematically retrieved. The two researchers independently screened the studies and extracted the data. Cochrane ROB tool was used to evaluate the quality of the studies, and Stata 14.0 software was used to conduct a network meta-analysis of neurological deficit score, activities of daily living (ADL), clinical effective rate and Fugl-meyer motor function evaluation (FMA). Results: A total of 401 studies were obtained, and 17 studies met the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) values of the four outcome indexes were all ranked by "Governor vessel acupuncture + Conventional neurology treatment(GVAc+CT) > Yangming meridian acupuncture + Conventional neurology treatment(YMAc+CT) > Conventional neurology treatment (CT)". Compared to YMAc+CT and CT, GVAc+CT had the best effect in reducing the degree of neurological deficit score (SMD = -0.72, 95%CI = [-1.22,-0.21] and SMD = -1.07,95%CI = [-1.45,-0.69], respectively) and promoting the recovery of ADL((SMD = 0.59,95%CI = [0.31,0.88] and SMD = 0.96,95%CI = [0.70,1.21], respectively). Compared to CT, GVAc+CT also had a better clinical effective rate in the treatment of AIS (RR = 1.14,95%CI = [1.04,1.25]). Conclusions: Governor vessel acupuncture combined with conventional neurology treatment has the best effect in reducing the degree of neurological deficit score and promoting the recovery of ADL in AIS patientscompared to YMAc+CT and CT. Governor Vessel acupuncture is the most preferable acupoint scheme for clinical acupuncture treatment of AIS. [ABSTRACT FROM AUTHOR]

Background and aim: Stroke is a serious threat to human life and health, and post-stroke insomnia is one of the common complications severely impairing patients' quality of life and delaying recovery. Early understanding of the relationship between stroke and post-stroke insomnia can provide clinical evidence for preventing and treating post-stroke insomnia. This study was to investigate the prevalence of insomnia in patients with stroke. Methods: The Web of Science, PubMed, Embase, and Cochrane Library databases were used to obtain the eligible studies until June 2023. The quality assessment was performed to extract valid data for meta-analysis. The prevalence rates were used a random-efect. I2 statistics were used to assess the heterogeneity of the studies. Results: Twenty-six studies met the inclusion criteria for meta-analysis, with 1,193,659 participants, of which 497,124 were patients with stroke. The meta-analysis indicated that 150,181 patients with stroke developed insomnia during follow-up [46.98%, 95% confidence interval (CI): 36.91–57.18] and 1806 patients with ischemic stroke (IS) or transient ischemic attack (TIA) developed insomnia (47.21%, 95% CI: 34.26–60.36). Notably, 41.51% of patients with the prevalence of nonclassified stroke developed insomnia (95% CI: 28.86–54.75). The incidence of insomnia was significantly higher in patients with acute strokes than in patients with nonacute strokes (59.16% vs 44.07%, P < 0.0001). Similarly, the incidence of insomnia was significantly higher in the patients with stroke at a mean age of ≥65 than patients with stroke at a mean age of <65 years (47.18% vs 40.50%, P < 0.05). Fifteen studies reported the follow-up time. The incidence of insomnia was significantly higher in the follow-up for ≥3 years than follow-up for <3 years (58.06% vs 43.83%, P < 0.05). Twenty-one studies used the Insomnia Assessment Diagnostic Tool, and the rate of insomnia in patients with stroke was 49.31% (95% CI: 38.59–60.06). Five studies used self-reporting, that the rate of insomnia in patients with stroke was 37.58% (95% CI: 13.44–65.63). Conclusions: Stroke may be a predisposing factor for insomnia. Insomnia is more likely to occur in acute-phase stroke, and the prevalence of insomnia increases with patient age and follow-up time. Further, the rate of insomnia is higher in patients with stroke who use the Insomnia Assessment Diagnostic Tool. [ABSTRACT FROM AUTHOR]

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis. Aims: We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS. Data sources & eligibility criteria: We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form. Results: The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies. Conclusion: Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease. [ABSTRACT FROM AUTHOR]

Epigallocatechin gallate (EGCG) is a polyphenolic component of green tea that has anti-oxidative and anti-inflammatory effects in neurons. Ischemic stroke is a major neurological disease that causes irreversible brain disorders. It increases the intracellular calcium concentration and induces apoptosis. The regulation of intracellular calcium concentration is important to maintain the function of the nervous system. Hippocalcin is a neuronal calcium sensor protein that controls intracellular calcium concentration. We investigated whether EGCG treatment regulates the expression of hippocalcin in stroke animal model and glutamate-induced neuronal damage. We performed middle cerebral artery occlusion (MCAO) to induce cerebral ischemia. EGCG (50 mg/kg) or phosphate buffered saline was injected into the abdominal cavity just before MCAO surgery. The neurobehavioral tests were performed 24 h after MCAO surgery and cerebral cortex tissue was collected. MCAO damage induced severe neurobehavioral disorders, increased infarct volume, and decreased the expression of hippocalcin in the cerebral cortex. However, EGCG treatment improved these deficits and alleviated the decrease in hippocalcin expression in cerebral cortex. In addition, EGCG dose-dependently alleviated neuronal cell death and intracellular calcium overload in glutamate-exposed neurons. Glutamate exposure reduced hippocalcin expression, decreased Bcl-2 expression, and increased Bax expression. However, EGCG treatment mitigated these changes caused by glutamate toxicity. EGCG also attenuated the increase in caspase-3 and cleaved caspase-3 expressions caused by glutamate exposure. The effect of EGCG was more pronounced in non-transfected cells than in hippocalcin siRNA-transfected cells. These findings demonstrate that EGCG protects neurons against glutamate toxicity through the regulation of Bcl-2 family proteins and caspase-3. It is known that hippocalcin exerts anti-apoptotic effect through the modulation of apoptotic pathway. Thus, we can suggest evidence that EGCG has a neuroprotective effect by regulating hippocalcin expression in ischemic brain damage and glutamate-exposed cells. [ABSTRACT FROM AUTHOR]

Background: The probability of motor deficits after stroke is relatively high. At the same time many studies have reported that acupuncture and rehabilitation therapy have a significant effect on the treatment of stroke. Objective: This systematic review and meta-analysis aimed to evaluate the clinical value of acupuncture and rehabilitation therapy on brain eloquent areas and neurological function in ischemic stroke. Methods: Seven databases were electronically searched to screen randomized controlled trials (RCTs) of different intervention methods (acupuncture, rehabilitation) in the treatment of ischemic stroke. The search time is from January 1, 2000 to April 20, 2023, and the search languages are limited to Chinese and English. Two researchers independently screened literature and extracted data. The methodological quality of the studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 17 randomized controlled studies were included, including 699 patients, with a maximum sample size of 144 cases and a minimum sample size of 11 cases. Among them, 3 studies reported the brain function in SM1 area. The effective rate of the experimental group was higher than that of the control group [relative risk (OR) = 3.24, 95%CI: 1.49 to 7.05, P < 0.05]. The FMA score of patients in the experimental group was higher than that in the control group [mean difference (MD) = 4.79, 95% CI: 3.86 to 5.71, P < 0.00001]. The NIHSS score of patients in the experimental group was lower than that in the control group [mean difference (MD) = -4.12, 95% CI: -6.99 to -1.26, P < 0.05].None of studies reported adverse events. Conclusions: Acupuncture rehabilitation for ischemic stroke can activate corresponding brain functional areas and improve neurological deficits. The therapeutic effect of acupuncture rehabilitation treatment is better than that of basic western medicine treatment, and it is more effective in improving neurological deficits. At the same time, clinical research needs to use high-quality randomized double-blind controlled trials with more detailed and larger sample designs, long-term efficacy evaluation and evidence-based research methods. [ABSTRACT FROM AUTHOR]

Background: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. Methods: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. Results: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. Conclusion: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US. [ABSTRACT FROM AUTHOR]

Objectives: Synthetic datasets are artificially manufactured based on real health systems data but do not contain real patient information. We sought to validate the use of synthetic data in stroke and cancer research by conducting a comparison study of cancer patients with ischemic stroke to non-cancer patients with ischemic stroke. Design: retrospective cohort study. Setting: We used synthetic data generated by MDClone and compared it to its original source data (i.e. real patient data from the Ottawa Hospital Data Warehouse). Outcome measures: We compared key differences in demographics, treatment characteristics, length of stay, and costs between cancer patients with ischemic stroke and non-cancer patients with ischemic stroke. We used a binary, multivariable logistic regression model to identify risk factors for recurrent stroke in the cancer population. Results: Using synthetic data, we found cancer patients with ischemic stroke had a lower prevalence of hypertension (52.0% in the cancer cohort vs 57.7% in the non-cancer cohort, p<0.0001), and a higher prevalence of chronic obstructive pulmonary disease (COPD: 8.5% vs 4.7%, p<0.0001), prior ischemic stroke (1.7% vs 0.1%, p<0.001), and prior venous thromboembolism (VTE: 8.2% vs 1.5%, p<0.0001). They also had a longer length of stay (8 days [IQR 3–16] vs 6 days [IQR 3–13], p = 0.011), and higher costs associated with their stroke encounters: $11,498 (IQR $4,440 –$20,668) in the cancer cohort vs $8,084 (IQR $3,947 –$16,706) in the non-cancer cohort (p = 0.0061). A multivariable logistic regression model identified 5 predictors for recurrent ischemic stroke in the cancer cohort using synthetic data; 3 of the same predictors identified using real patient data with similar effect measures. Summary statistics between synthetic and original datasets did not significantly differ, other than slight differences in the distributions of frequencies for numeric data. Conclusion: We demonstrated the utility of synthetic data in stroke and cancer research and provided key differences between cancer and non-cancer patients with ischemic stroke. Synthetic data is a powerful tool that can allow researchers to easily explore hypothesis generation, enable data sharing without privacy breaches, and ensure broad access to big data in a rapid, safe, and reliable fashion. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend the use of perfusion computed tomography (CT) to identify emergent large vessel ischemic stroke (ELVIS) patients who are likely to benefit from endovascular thrombectomy (EVT) if they present within 6–24 hour (late window) of stroke onset. We aim to determine if the interrater and intrarater reliability among physicians when recommending EVT is significantly different when perfusion CT or non-perfusion CT is reviewed. Methods: A total of 30 non-consecutive patients will be selected from our institutional database comprising 3144 cranial CT scans performed for acute stroke symptoms January 2018 to August 2022. The clinical and radiologic data of the 30 patients will be presented in random order to a group of 29 physicians in two separate sessions at least three weeks apart. In each session, the physicians will evaluate each patient once with automated perfusion images and once without. We will use non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). Discussion: The results obtained from this study, combined with the clinical outcomes data of patients categorized through the two imaging techniques and a cost-effectiveness analysis, will offer a comprehensive evaluation of the clinical utility of perfusion CT neuroimaging. Should there be no significant disparity in the reliability of decisions made by clinicians using the two neuroimaging protocols, it may be necessary to revise existing recommendations regarding neuroimaging in the later time window to align with these findings. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether abdominal adiposity has an additional effect on post-stroke outcomes. This study aimed to determine whether waist circumference (WC) is independently associated with clinical outcomes after acute ischemic stroke. Methods: We enrolled patients with acute ischemic stroke from a multicenter hospital-based stroke registry in Fukuoka, Japan. We measured WC on admission and categorized patients into four groups (Q1–Q4) according to the quartiles in females and males. The clinical outcomes were poor functional outcome (modified Rankin scale score 2–6) and death from any cause. Logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval of the outcomes of interest after adjusting for potential confounding factors, including body mass index (BMI). Results: A total of 11,989 patients (70.3±12.2 years, females: 36.1%) were included in the analysis. The risk of poor functional outcome significantly decreased for Q2–Q4 (vs. Q1) at discharge and Q2–Q3 (vs. Q1) at 3 months, even after adjusting for potential confounders, including BMI. In contrast, adjustment of BMI eliminated the significant association between WC and all-cause death at discharge and 3 months. The association between high WC and favorable functional outcome was not affected by fasting insulin levels or homeostatic model assessment for insulin resistance and was only found in patients without diabetes (P = 0.02 for heterogeneity). Conclusions: These findings suggest that abdominal adiposity has an additional impact on post-stroke functional outcome, independent of body weight and insulin action. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine whether post-stroke early body temperature is associated with neurological damage in the acute phase and functional outcomes at three months. Methods: We included 7,177 patients with acute ischemic stroke within 24 h of onset. Axillary temperature was measured daily in the morning for seven days. Mean body temperature was grouped into five quintiles (Q1: 35.1‒36.5°C, Q2: 36.5‒36.7°C, Q3: 36.7‒36.8°C, Q4: 36.8‒37.1°C, and Q5: 37.1‒39.1°C). Clinical outcomes included neurological improvement during hospitalization and poor functional outcome (modified Rankin scale score, 3–6) at three months. A logistic regression analysis was performed to evaluate the association between body temperature and clinical outcomes. Results: The patient's mean (SD) age was 70.6 (12.3) years, and 35.7% of patients were women. Mean body temperature was significantly associated with less neurological improvement from Q2 (odds ratios [95% confidence interval], 0.77 [0.65–0.99] vs. Q1) to Q5 (0.33 [0.28–0.40], P for trend <0.001) even after adjusting for potential confounders, including baseline neurological severity, C-reactive protein levels, and post-stroke acute infections. The multivariable-adjusted risk of poor functional outcome linearly increased from Q2 (1.36 [1.03–1.79]) to Q5 (6.44 [5.19–8.96], P for trend <0.001). These associations were maintained even in the analyses excluding patients with acute infectious diseases. Multivariable-adjusted risk of poor functional outcome was higher in patients with early body temperature elevation on days 1–3 and with longer duration with body temperature >37.0°C. Conclusions: Post-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Stroke-associated pneumonia (SAP) is a common complication of acute ischemic stroke (AIS). This single-center retrospective observational study aimed to identify factors associated with SAP and predictors of poor outcomes in hospitalized patients with AIS. The study included patients admitted to Chumphon Khet Udomsakdi Hospital in Thailand within 7 days of the onset of AIS between July 2019 and July 2020. The patients were divided according to whether they were diagnosed with SAP during hospitalization into a pneumonia group and a non-pneumonia (control) group. Factors associated with SAP were identified. After 3 months, the patients with AIS were divided into those with a poor outcome (modified Rankin scale [mRS] score ≥4) and those with a non-poor outcome (mRS score <4). Factors associated with a poor outcome were sought. During the study period, 342 patients (mean age 65 years, 61% men) were admitted with AIS, of whom 54 (15.8%) developed SAP. Multivariate analysis identified a failed water-swallowing test (WST; adjusted odds ratio [aOR] 87.48, 95% confidence interval [CI] 21.00–364.51, p<0.001), endotracheal intubation with invasive mechanical ventilation (aOR 12.38, 95% CI 2.44–101.35, p = 0.001), and a retained Foley catheter (aOR 5.67, 95% CI 2.03–15.83, p = 0.001) to be associated with SAP. Of the 342 patients, 112 (32.7%) had a poor outcome at 3 months, predictors of which included having hypertension as a comorbidity (aOR 2.87, 95% CI 1.18–6.98, p = 0.020), a pre-stroke mRS score ≥2 (aOR 4.53, 95% CI 1.50–12.72, p = 0.007), an initial Barthel Index score <40 (aOR 3.35, 95% CI 1.57–7.16, p = 0.002), a failed WST (aOR 5.04, 95% CI 2.00–12.74, p = 0.001), and brain edema (aOR 20.67, 95% CI 2.10–203.26, p = 0.009). This study emphasized the association of SAP with a failed WST, endotracheal intubation with invasive mechanical ventilation, and a retained Foley catheter but also identified hypertension, a pre-stroke mRS score ≥2, an initial BI score <40, a failed WST, and brain edema as predictors of a poor outcome for patients 3 months after AIS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Ginkgolide Meglumine Injection (GMI) combined with Butylphthalide in the treatment of Acute Ischemic Stroke (AIS), and provide reference for rational clinical medication. Methods: PubMed, Embase, Web of science, CNKI, Wanfang, VIP and other databases were searched for published studies on the treatment of AIS with GMI combined with Butylphthalide in both Chinese and English. The search period was from the establishment of the database to July 2023. The included studies that met the inclusion criteria were analyzed using RevMan 5.3 software for Meta-analysis. Results: A total of 25 studies involving 2362 patients (experimental group = 1182, control group = 1180) were included. The results of meta-analysis showed that the overall effective rate of the experimental group was significantly higher than that of the control group [RR = 1.21, 95% CI (1.16, 1.26), P< 0.00001]. In addition, compared with the control group, the experimental group showed significant improvement in NIHSS score [SMD = -1.59, % CI (-2.00–1.18), P< 0.00001] and ADL score [SMD = 2.12, 95% CI (1.52, -2.72), P<0.00001], significant decrease in CRP [SMD = -2.24, 95% CI (-3.31, -1.18), P<0.0001] and TNF-α [SMD = -2.74, 95% CI (-4.45, -1.03), P< 0.005] levels, and improvement in plasma viscosity [SMD = -0.86, 95% CI (-1.07, -0.66), P< 0.00001]. However, the influence on homocysteine level remains inconclusive. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups [SMD = 0.95, 95% CI (0.71, 1.28), P> 0.05]. Conclusion: GMI combined with Butylphthalide shows good clinical application effects and good safety in the treatment of AIS. However, more large-sample, multicenter, randomized controlled are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend the treatment of emergent large vessel ischemic stroke (ELVIS) patients presenting beyond 6 hours of last known well time with endovascular thrombectomy (EVT) based on perfusion computed tomography (CT) neuroimaging. We compared the outcomes (long-term good clinical outcomes, symptomatic intracranial hemorrhage (sICH), and mortality) of ELVIS patients according to the type of CT neuroimaging they underwent. Methods: We searched the following databases: Medline, Embase, CENTRAL, and Scopus from January 1, 2015, to June 14, 2023. We included studies of late-presenting ELVIS patients undergoing EVT that had with data for non-perfusion and perfusion CT neuroimaging. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random effects model. Results: We found 7 observational cohorts. Non-perfusion versus perfusion CT was not statistically significantly different for both long-term clinical (n = 3,224; RR: 0.96; 95% CI 0.86 to 1.06; I2 = 18%) and sICH (n = 3,724; RR: 1.08 95% CI 0.60 to 1.94; I2 = 76%). Perfusion CT had less mortality (n = 3874; RR: 1.22; 95% CI 1.07 to 1.40; I2 = 0%). The certainty of these findings is very low because of limitations in the risk of bias, indirectness, and imprecision domains of the Grading of Recommendations, Assessment, Development and Evaluations. Conclusion: The use of either non-perfusion or perfusion CT neuroimaging may have little to no effect on long-term clinical outcomes and sICH for late-presenting EVT patients. Perfusion CT neuroimaging may be associated with a reduced the risk of mortality. Evidence uncertainty warrants randomized trial data. [ABSTRACT FROM AUTHOR]

Background: Percutaneous closure of a patent foramen ovale (PFO) or the left atrial appendage (LAA) are controversial procedures to prevent stroke but often used in clinical practice. We assessed the regional variation of these interventions and explored potential determinants of such a variation. Methods: We conducted a population-based analysis using patient discharge data from all Swiss hospitals from 2013–2018. We derived hospital service areas (HSAs) using patient flows for PFO and LAA closure. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). SCV values >5.4 indicate a high and >10 a very high variation. Because the evidence on the efficacy of PFO closure may differ in patients aged <60 years and ≥60 years, age-stratified analyses were performed. We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors. Results: Overall, 2574 PFO and 2081 LAA closures from 10 HSAs were analyzed. The fully adjusted PFO and LAA closure rates varied from 3 to 8 and from 1 to 9 procedures per 100,000 persons per year across HSAs, respectively. The regional variation was high with respect to overall PFO closures (EQ 3.0, SCV 8.3) and very high in patients aged ≥60 years (EQ 4.0, SCV 12.3). The variation in LAA closures was very high (EQ 16.2, SCV 32.1). In multivariate analysis, women had a 28% lower PFO and a 59% lower LAA closure rate than men. French/Italian language areas had a 63% lower LAA closure rate than Swiss German speaking regions and areas with a higher proportion of privately insured patients had a 86% higher LAA closure rate. After full adjustment, 44.2% of the variance in PFO closure and 30.3% in LAA closure remained unexplained. Conclusions: We found a high to very high regional variation in PFO closure and LAA closure rates within Switzerland. Several factors, including sex, language area, and insurance status, were associated with procedure rates. Overall, 30–45% of the regional procedure variation remained unexplained and most probably represents differing physician practices. [ABSTRACT FROM AUTHOR]

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods. [ABSTRACT FROM AUTHOR]

Background: Labile blood pressure after acute ischaemic stroke requiring mechanical thrombectomy is independently associated with poor patient outcomes. Objectives: This study protocol describes is designed to determine whether transauricular nerve stimulation, improves baroreflex sensitivity, reduces blood pressure variability in the first 24 hours after acute ischaemic stroke requiring mechanical thrombectomy. Design: Phase 2A, proof-of-concept, sham-controlled randomised trial Methods and Analysis: 36 individuals undergoing mechanical thrombectomy for acute ischaemic stroke with established hypertension aged >18 years will be randomly allocated to receive bilateral active or sham transauricular nerve stimulation for the duration of the mechanical thrombectomy procedure (AffeX-CT/001 investigational device). The intervention will be repeated for 1h the morning following the mechanical thrombectomy. Non-invasive blood pressure will be measured ≥2h for 24h after mechanical thrombectomy. Holter electrocardiographic monitoring will be recorded during transauricular nerve stimulation. Participants, clinicians and investigators will be masked to treatment allocations. The primary outcome will be the coefficient of variation of systolic blood pressure. Secondary outcomes include additional estimates of blood pressure variability and time/frequency-domain measures of autonomic cardiac modulation An adjusted sample size of 36 patients is required to have a 90% chance of detecting, as significant at the 5% level, a difference in the coefficient of variation in systolic blood pressure of 5±4mmHg between sham and active stimulation [assuming 5% non-compliance rate in each group]. Ethics: confirmed on 16 March 2023 by HRA and Health and Care Research Wales ethics committee (reference 23/WA/0013) Discussion: This study will provide proof-of-concept data that examines whether non-invasive autonomic neuromodulation can be used to favourably modify blood pressure and autonomic control after acute ischaemic stroke requiring mechanical thrombectomy. Trial registration: Trial registration number:NCT05417009. [ABSTRACT FROM AUTHOR]