Although the gut microbiota and kynurenine (KYN) metabolism have significant protective effects against ischaemic stroke (IS), the exact mechanism has yet to be fully elucidated. Combined serum metabolomics and 16S rRNA gene sequencing were used to reveal the differences between the gut microbiota and metabolites in rats treated with or without blueberry extract. Faecal microbiota transplantation (FMT) was employed to validate the protective role of the gut microbiota in IS. Furthermore, the interaction between Prevotella and IS was also confirmed in patients. Rats with IS experienced neurological impairments accompanied by an impaired intestinal barrier and disturbed intestinal flora, which further contributed to heightened inflammatory responses. Furthermore, Prevotella played a critical role in IS pathophysiology, and a positive correlation between Prevotella and KYN was detected. The role of KYN metabolism in IS was further demonstrated by the finding that IDO was significantly upregulated and that the use of the IDO inhibitor, attenuated KYN metabolic pathway activity and ameliorated neurological damage in rats with IS. Prevotella intervention also significantly improved stroke symptoms and decreasing KYN levels in rats with IS. FMT showed that the beneficial effects of blueberry extract on IS involve gut bacteria, especially Prevotella, which were confirmed by microbiological analyses conducted on IS patients. Moreover, blueberry extract led to significant changes in kynurenic acid levels and tryptophan and IDO levels through interactions with Prevotella. Our study demonstrates for the first time that blueberry extract could modulate \"intestinal microecology-KYN metabolism\" to improve IS.

BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.
OBJECTIVE: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.
METHODS: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher\'s exact test for categorical data.
RESULTS: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288).
CONCLUSIONS: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

OBJECTIVE: This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i.
METHODS: Utilizing Taiwan\'s National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first.
RESULTS: After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation.
CONCLUSIONS: Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

BACKGROUND: Several prehospital scales have been designed to aid paramedics in identifying stroke patients in the ambulance setting. However, external validation and comparison of these scales are largely lacking.
OBJECTIVE: To compare all published prehospital stroke detection scales in a large cohort of unselected stroke code patients.
METHODS: We conducted a systematic literature search to identify all stroke detection scales. Scales were reconstructed with prehospital acquired data from two observational cohort studies: the Leiden Prehospital Stroke Study (LPSS) and PREhospital triage of patients with suspected STrOke (PRESTO) study. These included stroke code patients from four ambulance regions in the Netherlands, including 15 hospitals and serving four million people. For each scale, we calculated the accuracy, sensitivity and specificity for a diagnosis of stroke (ischemic, hemorrhagic or TIA). Moreover, we assessed the proportion of stroke patients who received reperfusion treatment with intravenous thrombolysis or endovascular thrombectomy that would have been missed by each scale.
RESULTS: We identified 14 scales, of which seven (CPSS, FAST, LAPSS, MASS, MedPACS, OPSS, and sNIHSS-EMS) could be reconstructed. Of 3317 included stroke code patients, 2240 (67.5%) had a stroke (1528 ischemic, 242 hemorrhagic, 470 TIA) and 1077 (32.5%) a stroke mimic. Of ischemic stroke patients, 715 (46.8%) received reperfusion treatment. Accuracies ranged from 0.60 (LAPSS) to 0.66 (MedPACS, OPSS and sNIHSS-EMS), sensitivities from 66% (LAPSS) to 84% (MedPACS and sNIHSS-EMS), and specificities from 28% (sNIHSS-EMS) to 49% (LAPSS). MedPACS, OPSS and sNIHSS-EMS missed the fewest reperfusion-treated patients (10.3-11.2%), whereas LAPSS missed the most (25.5%).
CONCLUSIONS: Prehospital stroke detection scales generally exhibited high sensitivity but low specificity. While LAPSS performed poorest, MedPACS, sNIHSS-EMS and OPSS demonstrated the highest accuracy and missed the fewest reperfusion-treated stroke patients. Use of the most accurate scale could reduce unnecessary stroke code activations for patients with a stroke mimic by almost a third, but at the cost of missing 16% of strokes and 10% of patients who received reperfusion treatment.

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BACKGROUND: Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies - including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR) - detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time.
OBJECTIVE: To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment.
METHODS: We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome.
RESULTS: Among 11840 patients receiving IVT, 2489/5503 (45.4%) women achieved favorable functional outcome compared to 3787/6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjOR 0.87, 95%CI 0.79-0.96, p=0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) 1.04, 95%CI 1.02-1.06, p<0.001) but not in women (adjOR (per year) 1.01, 95%CI 0.99-1.03, p=0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction and longer door-to-needle times were significantly associated with outcome only in women.
CONCLUSIONS: Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future.Data access statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (DM), access inquiries have to be addressed to the registry\'s academic review board.

UNASSIGNED: Patients with acute stroke are at risk of respiratory or circulatory compromise resulting in vital instability, which can be captured through the widely used aggregated National Early Warning Score (NEWS). We aimed to assess the relation between vital instability (defined as NEWS of five or higher) and death or dependency at 90 days after stroke.
UNASSIGNED: In this observational cohort study we studied 763 patients with ischaemic stroke (n = 400), intracerebral haemorrhage (ICH) (n = 146) or subarachnoid haemorrhage (SAH) (n = 217), hospitalized to a Dutch tertiary referral hospital from 1 January 2017 to 31 December 2018. We calculated NEWS for each 8 h time span during the first 72 h after hospitalization. We also decomposed NEWS into its three components respiration, circulation and consciousness. The primary outcome was death or dependency (modified Rankin Scale score ⩾3) at 90 days after stroke. The association of vital instability with functional dependency was examined using Poisson regression.
UNASSIGNED: Two hundred and twenty-seven (58%) patients with ischaemic stroke, 101 (69%) with ICH and 142 (65%) with SAH had at least one episode of vital instability. In patients with ischaemic stroke or SAH, vital instability was associated after adjustment for confounders with death or dependency (adjusted relative risk 1.55 ((95% CI) 1.25-1.93 and 2.13 (1.35-3.36), respectively)). This was mainly driven by impaired consciousness, which was associated with death or dependency in all types of stroke. Respiratory insufficiency and circulatory instability were associated with death or dependency only in SAH.
UNASSIGNED: Vital instability in the first 72 h of hospitalization for ischaemic stroke or SAH is associated with death or dependency at 90 days. Impaired consciousness was the main driver of this relationship. NEWS may not be appropriate for patients with acute stroke, mainly due to the dichotomous manner in which the level of consciousness is classified, and modification of NEWS should be considered for these patients.

UNASSIGNED: Growing evidence suggests that concurrent ischaemic stroke (IS) exacerbates the prognosis of patients with dilated cardiomyopathy (DCM) and that this effect may be further influenced by sex. However, the exact effect of sex remains unclear. This study aimed to explore the effects of the relevant risk factors on the prognosis of patients with DCM and concurrent IS. Considering the sex differences in DCM, this study further investigated the impact of concurrent IS on the prognosis of men and women with DCM.
UNASSIGNED: A total of 632 patients with DCM enrolled between 2016 and 2021 were included in this study. Clinical data were obtained from medical records, and all participants were followed up in the outpatient clinic or by telephone for at least 1 year. A Cox proportional hazards model and Kaplan-Meier curves were used to evaluate the effects of concurrent IS on the prognosis of patients with DCM.
UNASSIGNED: Patients with DCM complicated with IS (DCM-IS) had significantly lower cumulative survival rates than patients with DCM without IS (non-IS) (74.6% vs. 84.2%, χ 2 = 6.85, p = 0.009). Additionally, IS was associated with greater risks of death and heart transplantation (HTx) in men (75.8% vs. 85.1%, χ 2 = 5.02, p = 0.025), but not in women (71.0% vs. 81.5%, χ 2 = 1.91, p = 0.167).
UNASSIGNED: This large-scale multicentre prospective cohort study demonstrated a poorer prognosis in patients with concurrent DCM and IS, particularly among men. Patients with DCM should not be overlooked in IS screening, emphasis should be placed on the occurrence of IS in patients with DCM. Early and proactive secondary prevention of cerebrovascular diseases might improve the prognosis of DCM patients. More intervention studies focusing on men with DCM complicated with IS should be prioritised.

BACKGROUND: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized.
METHODS: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT registry were analyzed. The study included 1,568 patients from 37 academic centers across North America, Asia, and Europe, treated with mechanical thrombectomy (MT), with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021.
RESULTS: Among the 1,568 patients, 347 (22.2%) experienced very poor outcomes (mRS 5-6). Key predictors of poor outcomes were advanced age (OR: 1.03; 95% CI: 1.02 to 1.04; p < 0.001), higher baseline NIHSS scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver operating characteristic (ROC) curve of 0.76.
CONCLUSIONS: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

BACKGROUND: Stroke risks associated with rapid climate change remain controversial due to a paucity of evidence.
OBJECTIVE: To examine the risk of subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), and ischemic stroke (IS) associated with meteorological parameters.
METHODS: In this time-stratified case-crossover study, adult patients hospitalized for their first stroke between 2011 and 2020 from the insurance claims data in Taiwan were identified. The hospitalization day was designated as the case period, and three or four control periods were matched by the same day of the week and month of each case period. Daily mean and 24-hour variations in ambient temperature, relative humidity, air pressure, and apparent temperature were measured. Conditional logistic regression models were applied to assess the risk of stroke associated with exposure to weather variables, using the third quintile as a reference, controlling for air pollutant levels.
RESULTS: There were 7161 patients with SAH, 40,426 patients with ICH, and 107,550 patients with IS. There was an inverse linear relationship between mean daily temperature and apparent temperature with ICH. Elevated mean daily atmospheric pressure was associated with an increased risk of ICH. A greater decrease in apparent temperature over a 24-hour period was associated with increased risk of ICH but decreased risk of IS (odds ratio [95% confidence interval] for the first vs. third quintile of changes in apparent temperature, 1.141 [1.053-1.237] and 0.946 [0.899-0.996], respectively).
CONCLUSIONS: There were considerable differences in short-term associations between meteorological parameters and three main pathological types of strokes.Data access statement: The authors have no permission to share the data.