Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation.

Incidence and Outcomes of Patients With Early Cardiac Complications After Intracerebral Hemorrhage: A Report From VISTA.

BACKGROUND: The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data. METHODS: We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort. RESULTS: We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1-88.6] versus 83.6% [95% CI, 81.2-86.0]; P=0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group (P<0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]; P<0.001). CONCLUSIONS: Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS.

Fluoxetine promotes the recovery of dysphagia and improves nutritional status and neurotrophic status in dysphagia patients after acute ischemic stroke.

This study aimed to investigate the effects of fluoxetine on swallowing function, neurotrophic factors, and psychological status in patients with dysphagia after acute ischemic stroke (AIS). A total of 118 patients with dysphagia after AIS who were diagnosed and treated in our hospital from July 2020 to March 2022 were selected as the study objects with 59 cases in each group. Patients in the control group underwent routine treatment and swallowing rehabilitation without fluoxetine. Patients in the study group received routine treatment, swallowing rehabilitation, and fluoxetine treatment. The quality of life was compared according to the Generic Quality of Life Inventory-74 (CQOLI-74). Patients were followed for 90 days, and the grades were compared with the Modified Rankin Scale (mRS). The total effective rate of the study group was 84.75%, which was higher than that of the control group with 62.71% (χ2 = 7.394, P < 0.05). The life quality scores of the two groups were both dramatically elevated compared to those before the treatment, and the study group had a sensibly higher life quality score than the control group (P < 0.05). The proportion of grade 4~5 in the study group was significantly lower than that in the control group (χ2 = 492, P < 0.05). The total incidence of adverse reactions in the control group was 5.08% (3/59), which was significantly lower than that in the study group with 11.86% (7/59) (χ2 = 1.748, P = 0.186). Fluoxetine has a significant effect on the treatment of dysphagia after AIS by enhancing the recovery of dysphagia and promoting the recovery of neurological function.

Definitions of white matter hyperintensity change: impact on estimates of progression and regression.

BACKGROUND: White matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression. METHODS: We recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1-3 months after stroke and 1 year later. We assessed WMH volume (in absolute mL and % intracranial volume) and applied four different definitions, including two thresholds (based on SD or mL), percentile and quintile approaches. RESULTS: In 198 participants, mean age 65.5 (SD=11.13), baseline WMH volume was 15.46 mL (SD=19.2), the mean net WMH volume change was 0.98 mL (SD=2.84), range -7.98 to +12.84 mL. Proportion regressing/stable/progressing WMH were threshold 1 (SD), 29.8%/55.6%/14.6%; threshold 2(mL), 29.8%/16.7%/53.5%; percentile approach, 28.3%/21.2%/50.5%. The quintile approach includes five groups with quintile 3 reflecting no change (N=40), quintiles 1 and 2 any WMH decrease (N=80) and quintiles 4 and 5 any WMH increase (N=78). CONCLUSIONS: Different WMH change definitions cause big differences in how participants are categorised; additionally, non-normal WMH distribution precludes use of some definitions. Consistent use of an appropriate definition would facilitate data comparisons, particularly in clinical trials of potential WMH treatments.

Home and workforce reintegration one year after thrombectomy in acute stroke patients.

INTRODUCTION: Endovascular thrombectomy (EVT) combined with intravenous thrombolysis is the current standard treatment for acute large-vessel occlusion stroke. Beyond clear clinical benefits in the acute and post-acute phases, comprehensive evaluations of long-term outcomes, including home and workforce reintegration, remain limited. This study aimed to assess home and workforce reintegration 1 year post-EVT in a cohort of acute stroke patients and explore their association with health-related quality of life (HRQoL). PATIENTS AND METHODS: We conducted a prospective observational study of 404 patients undergoing EVT at a tertiary university medical center between October 2019 and December 2021. Patients' functional outcomes were evaluated using the modified Rankin Scale (mRS), and HRQoL was assessed via the European Quality of Life Five Dimension Scale (EQ-5D). Data on occupational and living status were collected through standardized telephone interviews at 3- and 12-months post-treatment. RESULTS: Of 357 patients with 12-month follow-up data, 33.6% had a favorable outcome (mRS 0-2). Among stroke survivors, the rate of home reintegration without nursing care was 42.1%, and workforce reintegration among previously employed patients was 43.3% at 12 months. Both outcomes were significantly associated with improved HRQoL. Lower neurological deficits and younger age were predictive of successful home and workforce reintegration. DISCUSSION AND CONCLUSION: One year post-EVT, approximately 40%-50% of acute stroke patients successfully reintegrate into home and work settings. These findings underscore the need for ongoing support tailored to improving long-term reintegration and quality of life for stroke survivors. DATA ACCESS STATEMENT: The data supporting the findings of the study are available from the corresponding author upon reasonable request and in accordance to European data privacy obligations.

Safety and Effectiveness Analysis of Endovascular Treatment vs Standard Medication Treatment in Patients with Progressive AIS-LVO Stroke in the Ultra-late Time Window: A Propensity Score Matched Cohort Study.

BACKGROUND AND PURPOSE: The time from onset to symptom deterioration in ischemic stroke often exceeds 24 hours, and this ultra-late time window is excluded from the endovascular treatment (EVT) guideline. This study aimed to explore the safety and efficacy of EVT in progressive acute ischemic stroke with large vessel occlusion (AIS-LVO) stroke patients with onset to symptom deterioration times of 24h-7 days. METHODS: Progressive stroke patients with time window of 24h-7 days treated at our hospital over the past 6 years were retrospectively collected. Patients were categorized into EVT and standard medication treatment (SMT) group based on the treatment approach. Patients were matched using propensity score matching (PSM). Safety outcomes primarily included 3-month mortality and symptomatic intracranial hemorrhage (sICH), efficacy outcome primarily included functional independence (3-month mRS≤2). RESULTS: A total of 396 patients were included in the study, with 86(21.7%) in EVT and 310(78.3%) in SMT group. There were 140 remaining after PSM, with 70 in each group (50%). Compared to SMT group, EVT group had higher functional independence (52.9% vs 15.7%, OR=7.504, 95% CI 2.141-14.093, P<0.001) and lower 3-month mortality (14.3% vs 40.0%, OR=0.412, 95% CI 0.099-0.856, P<0.001). EVT was also associated with higher sICH (25.7% vs 5.7%, OR=9.926, 95% CI 1.874-36.547, P<0.001). CONCLUSION: For patients with progressive AIS-LVO in the ultra-late time window, EVT remains a viable treatment approach.

Association of Alkaline Phosphatase Level with Futile Recanalization in Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy.

OBJECTIVE: Nearly half of Acute Ischemic Stroke (AIS) patients failed to achieve favorable outcomes despite successful reperfusion treatment. This phenomenon is referred to as Futile Recanalization (FR). Screening patients at risk of FR is vital for stroke management. Previous studies reported the diagnostic value of alkaline phosphatase (ALP) levels in certain aspects of stroke prognosis. However, the association between serum ALP level and FR among AIS patients treated with thrombectomy remained unclear. METHODS: We screened stroke patients who underwent thrombectomy at our center from January 2017 to June 2021, and those who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score=3) were ultimately analyzed. Demographic information, vascular risk factors, and laboratory test results were collected at admission. The 3-month unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6. The effect of ALP levels on FR was investigated with a logistic regression model. RESULTS: Of 788 patients who underwent thrombectomy, 277 achieved successful reperfusion. Among them, 142 patients (51.3%) failed to realize favorable outcomes at 3 months. After adjusting for confounding variables, higher ALP levels (p =0.002) at admission were independently associated with unfavorable outcomes at three months. Adding ALP values to conventional risk factors improved the performance of prediction models for FR. CONCLUSION: The current study found that the serum ALP levels at admission emerged as a potential biomarker for futile reperfusion in stroke patients undergoing thrombectomy. Further studies are warranted to confirm the clinical applicability of ALP level for futile recanalization prediction.

Machine learning approaches to identify the link between heavy metal exposure and ischemic stroke using the US NHANES data from 2003 to 2018.

Purpose: There is limited understanding of the link between exposure to heavy metals and ischemic stroke (IS). This research aimed to develop efficient and interpretable machine learning (ML) models to associate the relationship between exposure to heavy metals and IS. Methods: The data of this research were obtained from the National Health and Nutrition Examination Survey (US NHANES, 2003-2018) database. Seven ML models were used to identify IS caused by exposure to heavy metals. To assess the strength of the models, we employed 10-fold cross-validation, the area under the curve (AUC), F1 scores, Brier scores, Matthews correlation coefficient (MCC), precision-recall (PR) curves, and decision curve analysis (DCA) curves. Following these tests, the best-performing model was selected. Finally, the DALEX package was used for feature explanation and decision-making visualization. Results: A total of 15,575 participants were involved in this study. The best-performing ML models, which included logistic regression (LR) (AUC: 0.796) and XGBoost (AUC: 0.789), were selected. The DALEX package revealed that age, total mercury in blood, poverty-to-income ratio (PIR), and cadmium were the most significant contributors to IS in the logistic regression and XGBoost models. Conclusion: The logistic regression and XGBoost models showed high efficiency, accuracy, and robustness in identifying associations between heavy metal exposure and IS in NHANES 2003-2018 participants.

Reconstruction of quality marker system for Ginkgo Folium tablet using UHPLC-Q-Orbitrap MS, quantum chemical calculation, network pharmacology, and molecular simulation.

INTRODUCTION: Ginkgo Folium tablet (GFT) is a patented traditional Chinese medicine prepared from Ginkgo biloba leaves extract (GBE). However, the current quality indicators for GFT or GBE as designated by the Chinese Pharmacopoeia are insufficient in preventing counterfeit events. OBJECTIVE: This study aimed to putatively identify compounds in GFT and to further develop a quality marker (Q-marker) system for GFT. METHODS: A novel strategy utilizing database-aided ultrahigh-performance liquid chromatography-quadrupole-orbitrap mass spectrometry was employed to analyze the lyophilized aqueous powder of GFT. Subsequently, the identified compounds underwent quantum chemical calculations, network pharmacology, and molecular simulations through in silico approaches to evaluate the Q-marker principles of traceability, specificity, and efficiency-relevance. RESULTS: The results revealed the putative identification of a total of 66 compounds, including 36 flavonoids, 7 phenolic acids and derivatives, 5 terpene lactones, 4 fatty acids and derivatives, 3 alkaloids, 1 amino acid, and 10 other compounds. Particularly, 16 compounds were unexpectedly observed, and seven compounds met the Q-marker principles. CONCLUSION: This study recommends the seven compounds, namely, (-)-gallocatechin, matrine, (-)-epicatechin, ginkgolide C, ginkgolide A, ginkgolide B, and curdione, as the anti-counterfeiting pharmacopoeia Q-markers for GFT. The reconstruction of the Q-marker system for GFT not only enhances the understanding of the compounds in GFT and other GBE-based preparations but also provides valuable recommendations for the Pharmacopoeia Commission.

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Background: Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. Results: The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. Conclusion: The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Thrombectomy for patients with a large infarct core: a study-level meta-analysis with trial sequential analysis.

Background: The effectiveness and safety of endovascular treatment compared with medical management alone regarding outcomes for patients with a large infarct core remain uncertain. Objectives: To juxtapose the clinical outcomes of thrombectomy versus the best medical care in patients with a large infarct core. Design: Systematic review and meta-analysis. Data sources and methods: We conducted searches in PubMed, Cochrane, and Embase for articles published up until November 8, 2023. Randomized trials were selected for inclusion if they encompassed patients with large vessel occlusion and sizable strokes receiving thrombectomy. The primary outcome was functional outcomes at 3 months after pooling data using random-effects modeling. Safety outcomes included mortality at 3 months, symptomatic intracranial hemorrhage (SICH), and decompressive craniectomy. We performed a trial sequential analysis to balance type I and II errors. Results: From 904 citations, we identified six randomized trials, involving a cohort of 1897 patients with a large ischemic region. Of these, 953 individuals underwent endovascular thrombectomy. At 3 months, thrombectomy was significantly correlated with better neurological prognosis, as evidenced by the increased odds of good functional outcomes (odds ratio (OR), 2.90; 95% confidence interval (CI), 2.08-4.05) and favorable functional outcomes (OR, 2.40; 95% CI, 1.86-3.09). Mortality rates did not demonstrably diminish as a consequence of the endovascular management (OR, 0.78; 95% CI, 0.58-1.06). However, the incidence of SICH was greater in the thrombectomy group compared to those with only medical treatment (5.5% vs 3.2%; OR, 1.77; 95% CI, 1.11-2.83). The application of trial sequential analysis yielded definitive evidence regarding favorable function outcomes and a shift in the distribution of modified Rankin scale scores at 3 months; however, others remained inconclusive. Conclusion: The results from most of the included trials display consistency. Meta-analysis of these six randomized trials offers high-quality evidence that thrombectomy significantly mitigates disability in patients with a large infarction, while also increasing the risk of SICH. Trial registration: PROSPERO, CRD42023480359.

Dynamic changes in Beclin-1, LC3B, and p62 in aldose reductase-knockout mice at different time points after ischemic stroke.

Ischemic stroke is a brain injury caused by cerebral blood circulation disorders and is closely related to oxidative stress. Aldose reductase (AR) is a critical enzyme involved in oxidative stress. Autophagy has previously been found to play a key role in cerebral ischemia‒reperfusion injury. However, it is still unclear how autophagy molecules change after cerebral ischemia‒reperfusion injury in AR knockout mice (AR-/-). A transient middle cerebral artery occlusion (tMCAO) model was generated in AR-/- mice, and the neurological deficit scores of the mice were observed and recorded on Days 1, 3 and 5 after tMCAO. Neuronal damage in the ischemic penumbra was observed by TTC, HE, and Nissl staining. The expression of the autophagy-related molecules Beclin-1, LC3II/I, and P62 as well as that of molecules related to inflammation, oxidative stress, and neurological damage was detected by RT‒qPCR, western blotting, and immunofluorescence. Autophagosomes were observed using a transmission electron microscope. Cerebral ischemia‒reperfusion injury caused neurological deficits and ischemic infarction in tMCAO mice (P < 0.01). Beclin-1, Bcl2/Bax, SOD, GSH-px, P62, PSD95, and TOM20 levels decreased (P < 0.05), while IL-6, LC3II/I, and GFAP levels increased (P < 0.01) in the AR-/- tMCAO-1d group and the AR-/- tMCAO-3d group, compared to those in the sham group. Beclin-1, Bcl2/Bax, NOX4, GSH-px, P62, and PSD95 levels increased (P < 0.01), while IL-6, LC3II/I, and GFAP levels decreased (P < 0.01) in the AR-/- tMCAO-5d group compared to those in the AR-/- tMCAO-1d group. Autophagosome formation was observed in tMCAO mice. In summary, the changes in autophagy proteins in the brain tissue of the AR-/- mice after tMCAO were more obvious on Days 1 and 3 after tMCAO. The expression of Beclin-1 and P62 decreased, and the expression of LC3B increased after cerebral ischemia‒reperfusion injury in AR-/- mouse brain tissue.

Updated evidence of the Naoshuantong capsule against ischemic stroke: a systematic review and meta-analysis of randomized controlled trials.

Background: Stroke is a serious health issue that can result in death or disability, leading to a significant economic strain on society and families. A growing number of studies have shown that the Naoshuantong capsule (NSTC) is beneficial as a treatment for ischemic stroke (IS) in recent years. Our study aims to provide an update on the safety and efficacy of the NSTC in IS patients. Methods: We thoroughly searched eight databases to identify suitable randomized controlled trials (RCTs) assessing the effectiveness of the NSTC in the treatment of IS. The National Institute of Health Stroke Scale (NIHSS) for an acute period and modified Rankin Scale (mRS) at 3 months for a non-acute period were considered the primary outcome, and secondary outcomes included the NIHSS for a non-acute period, mRS, Barthel Index (BI), modified Barthel Index (MBI), Stroke-specific Quality of life (SS-QOL), and the recurrence rate of cerebrovascular events. Subsequently, its quality was assessed using the Cochrane risk assessment scale. Statistical analysis was conducted using RevMan 5.3 and Stata 14.0. Results: A total of 27 RCTs were included, which involved 3,139 patients. The results showed that the NSTC improved neurological function not only in the acute period (MD = -2.53; 95% CI: -2.91, -2.15; p < 0.00001) but also in the non-acute period (MD = -3.70; 95% CI: -5.82, -1.58; p = 0.0006) and improved the long-term functional outcomes with lower mRS scores (MD = -0.68; 95% CI: -1.09, -0.26; p = 0.001). At the same time, the NSTC decreased the risk of cerebrovascular disease recurrence (RR = 0.43; 95% CI: 0.27, 0.70; p = 0.0006) and increased the quality of life in the acute period (MD = 23.88; 95% CI: 16.63, 31.13; p < 0.00001). Significant disparities in the incidence of adverse events between the NSTC and control groups were not observed. The certainty of evidence was estimated as moderate to very low. Conclusion: The NSTC emerges as a potentially efficacious and safe treatment option for IS. NSTC could improve neurological function in different period of IS, and it has certain clinical value in secondary prevention. As a result of the poor quality and heterogeneity of the included trials, larger and standardized RCTs are needed to validate NSTC in IS treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=482981, identifier CRD42023482981.

Evaluating Retinal Blood Vessels for Predicting White Matter Hyperintensities in Ischemic Stroke: A Deep Learning Approach.

OBJECTIVE: This study aims to investigate whether a deep learning approach incorporating retinal blood vessels can effectively identify ischemic stroke patients with a high burden of White Matter Hyperintensities (WMH) using Nuclear Magnetic Resonance Imaging (MRI) as the gold standard. METHODS: In this cross-sectional study, we evaluated 263 ischemic stroke inpatients who had acquired both retinal fundus images and MRI images. The primary outcome was the diagnostic WMH on MRI brain, defined as different degrees of the age-related white matter changes (ARWMC) grade (<2 or ≥2). We developed a deep-learning network model with retinal fundus images to estimate WMH. RESULTS: The mean age of the patient cohort was 60.8 years, with 196 individuals (74.5%) being male. The prevalence of risk factors was as follows: hypertension in 237 (90.1%), diabetes in 109 (41.4%), hyperlipidemias in 84 (31.9%), coronary heart disease in 37 (14.1%), hyperhomocysteinemia in 70 (26.6%), and hyperuricemia in 73 (27.8%). Severe WMH defined as global ARWMC grade ≥2 was found in 139 (52.9%) participants. Using binocular fundus images, we achieved an F1 score of 0.811 and a Macro Accuracy of 0.811 in the ARWMC classification task. Additionally, we conducted experiments by progressively occluding fundus images to assess the relationship between different areas of the fundus images and ARWMC prediction. INTERPRETATION: Our study presents a novel deep learning model designed to detect a high burden of WMH using binocular fundus images in ischemic stroke patients. We have conducted initial investigations into the predictive significance of various fundus image areas for WMH identification. These findings underscore the need for broader data collection, further model training, and prospective data validation.

Predicting Poststroke Cognitive Impairment after Acute Ischemic Stroke Based on Admission Characteristics.

OBJECTIVE: This study aimed to develop a robust clinical prediction model for Poststroke cognitive impairment (PSCI) within 6 months following acute ischemic stroke (AIS) and subsequently validate its effectiveness. METHODS: A total of 386 AIS patients were divided into the PSCI group (174 cases) and the cognitively normal (CN) group (212 cases) based on the occurrence of PSCI. These patients were further categorized into two cohorts: 270 AIS patients in the training set, 116 AIS patients in the validation set. Multifactor logistic regression analysis was performed to identify independent predictors, which were then included in the prediction model for further analysis and validation. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), calibration plots analyses to assess discrimination, calibration ability, respectively. RESULTS: Based on the selected variables (smoking, alcohol consumption, female gender, low education level, NIHSS score at admission, stroke progression, high systolic blood pressure, diabetes, atrial fibrillation, coronary heart disease, low-density lipoprotein cholesterol, ß2-microglobulin, and Lp-PLA2), a clinical prediction model for the occurrence of PSCI within 6 months in AIS patients was constructed. The AUC-ROC of the model was 0.862, 0.806 in the training, validation sets, respectively. Calibration curve analyses and Hosmer-Lemeshow goodness-of-fit tests, along with other validation metrics, further demonstrated the model's good predictive performance. CONCLUSION: The model exhibits high discriminative ability for PSCI and has substantial guiding value for clinical decision-making. However, further optimization of the model is required with multicenter data to enhance its robustness and applicability.

Gut microbiota and functional outcome after ischemic stroke: a Mendelian randomization study.

Background: Previous studies have shown that gut microbiota dysbiosis could affect clinical prognosis through an unknown mechanism. However, the causal relationship between the gut microbiota and the functional outcome after ischemic stroke remains unclear. We aimed to investigate the causal association between the gut microbiota and the functional outcome after ischemic stroke using Mendelian randomization (MR). Methods: Genetic instrumental variables associated with 211 bacterial traits were obtained from the MiBioGen consortium (N = 18,340). Data from genome-wide association studies (GWAS) for functional outcome after ischemic stroke were obtained from two phenotypes (i.e., overall stroke outcome and motor recovery). The inverse variance weighted method was used to estimate the causal association. Enrichment analysis was conducted based on the results of the MR analyses. Results: The genetically predicted family Peptostreptococcaceae (OR = 0.63, 95% CI = 0.41-0.98, p = 0.038) and the genera LachnospiraceaeNK4A136 group (OR = 0.65, 95% CI = 0.43-1.00, p = 0.048), LachnospiraceaeUCG004 (OR = 0.54, 95% CI = 0.33-0.90, p = 0.017), and Odoribacter (OR = 0.40, 95% CI = 0.21-0.77, p = 0.006) presented a suggestive association with favorable functional outcome, while the genera Eubacterium oxidoreducens group (OR = 1.77, 95% CI = 1.11-2.84, p = 0.018) and RuminococcaceaeUCG005 (OR = 1.85, 95% CI = 1.15-2.96, p = 0.010) were associated with unfavorable functional outcome. The genetically predicted family Oxalobacteraceae (OR = 2.12, 95% CI = 1.10-4.11, p = 0.025) and the genus RuminococcaceaeUCG014 (OR = 4.17, 95% CI = 1.29-13.52, p = 0.017) showed a suggestive association with motor recovery, while the order Enterobacteriales (OR = 0.14, 95% CI = 0.02-0.87, p = 0.035) and the family Enterobacteriaceae (OR = 0.14, 95% CI = 0.02-0.87, p = 0.035) were associated with motor weakness. Enrichment analysis revealed that regulation of the synapse structure or activity may be involved in the effect of the gut microbiota on the functional outcome after ischemic stroke. Conclusions: This study provides genetic support that the gut microbiota, especially those associated with short-chain fatty acids, could affect stroke prognosis by mediating synapse function. Our findings suggest that modifying the composition of the gut microbiota could improve the prognosis of ischemic stroke.

Thrombolysis in wake-up stroke based on MRI mismatch.

OBJECTIVES: Wake-up stroke (WUPS) patients can be selected to intravenous thrombolysis (IVT) treatment based on the Magnetic Resonance Imaging (MRI) mismatch concept. However, recent studies suggest the introduction of modified MRI mismatch criteria, allowing IVT in WUPS patients with a partial mismatch. MATERIAL AND METHODS: WUPS patients treated with IVT in the NOR-TEST trial and consecutively thereafter at Stavanger University Hospital were included in this study. Patient selection for treatment was performed based on the clinical presentation and the MRI DWI/FLAIR mismatch criteria. MRI examinations were reassessed according to the modified DWI-FLAIR mismatch criteria, allowing partial mismatch. Improvement in NIHSS and mRS at 3 months were used to analyze clinical outcome, and the rate of intracranial hemorrhage (ICH) to analyze safety. RESULTS: 78 WUPS patients were treated with IVT. Only 68 of these patients were independent pre-stroke and included in the clinical analysis. When reassessing the MRI examinations, 41 (60 %) were rated as DWI/ FLAIR mismatch, 14 (21 %) as partial mismatch and 13 (19 %) as match. The results show that the patient groups had a mRS score 0-1 at 3 months measured as primary outcome to respectively 27 (65.9 %), 11 (78.6 %) and 8 (61.5 %); (P = 0.629). The mismatch group showed the best clinical improvement (3-points NIHSS reduction, p = 0.005). No ICH was seen in any of the groups. CONCLUSION: Our study extended the mismatch concept in clinical praxis to treat WUPS patients with partial mismatch, showing the best clinical outcome in the mismatch group.