OBJECTIVE: Guidelines help physicians to provide optimal care for stroke patients, but implementation is challenging due to the quantity of recommendations. Therefore a practical overview related to applicability of recommendations can be of assistance.
METHODS: A systematic review was performed on ischaemic stroke guidelines published in scientific journals, covering the whole acute care process for patients with ischaemic stroke. After data extraction, experts rated the recommendations on dimensions of applicability, that is, actionability, feasibility and validity, on a 9-point Likert scale. Agreement was defined as a score of ≥8 by ≥80% of the experts.
RESULTS: Eighteen articles were identified and 48 recommendations were ultimately extracted. Papers were included only if they described the whole acute care process for patients with ischaemic stroke. Data extraction and analysis revealed variation in terms of both content and comprehensiveness of this description. Experts reached agreement on 34 of 48 (70.8%) recommendations in the dimension actionability, for 16 (33.3%) in feasibility and for 15 (31.3%) in validity. Agreement on all three dimensions was reached for seven (14.6%) recommendations: use of a stroke unit, exclusion of intracerebral haemorrhage as differential diagnosis, administration of intravenous thrombolysis, performance of electrocardiography/cardiac evaluation, non-invasive vascular examination, deep venous thrombosis prophylaxis and administration of statins if needed.
CONCLUSIONS: Substantial variation in agreement was revealed on the three dimensions of the applicability of recommendations. This overview can guide stroke physicians in improving the care process and removing barriers where implementation may be hampered by validity and feasibility.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, and is associated with a significant risk of thromboembolic events. Left atrial appendage occlusion (LAAO) has emerged as a promising alternative for patients with contraindications or intolerance to anticoagulant therapy. This review summarises the current evidence, indications, and technical advancements in surgical and percutaneous LAAO. Preprocedural planning relies on various imaging techniques, each with unique advantages and limitations. The existing randomised clinical trials and meta-analyses demonstrate favourable results for both percutaneous and surgical LAAO. Postprocedural management emphasises personalised anticoagulation strategies and comprehensive imaging surveillance to ensure device stability and detect complications. Future focus should be put on antithrombotic regimens, investigating predictors of device-related complications, and simplifying procedural aspects to enhance patient outcomes. In summary, LAAO is presented as a valuable therapeutic option for preventing AF-related thromboembolic events, with ongoing research aimed at refining techniques and improving patient care.

OBJECTIVE: The aim of the study was to synthesize the body of knowledge on the factors that are important to the process of returning to work after ischaemic stroke in young adults under 55 years of age.
METHODS: Guidelines regarding the scoping review methodology developed by the Joanna Briggs Institute, and the PRISMA checklist for scoping reviews were used. A total of 2,249 studies were identified through a bibliographic search in six databases.
RESULTS: A total of ten studies were finally selected to respond to the research questions. Eight studies were quantitative observational studies, and two studies had a case study design. The rate of returning to work varied between the studies. The frequency of returning to work in young stroke patients, independent of the time of assessment, ranged from 42.4% to 86%. Returning to work after ischaemic stroke in young adults is a complex process and multidimensional problem which is affected by clinical variables (level of neurological deficits, cognitive ability, independency in activities of daily living, fatigue and depression, cardiovascular factors), as well as the socioeconomic and occupational status.
CONCLUSIONS: There is insufficient evidence concerning interventions promoting return to work. Future studies should focus on examining effective interventions to help young stroke survivors return to work.

OBJECTIVE: To our knowledge, there is no systematic review examining CVD risks after a SARS-CoV-2 infection over time, while also taking into account disease severity. All evidence on the risk for pulmonary embolism (PE), myocardial infarction (MI), ischaemic stroke (IS), haemorrhagic stroke (HS), and arterial thrombosis following infection was evaluated.
METHODS: The protocol was registered with PROSPERO. We searched Pubmed, Embase, MedRxiv and screened the titles/abstracts and full texts. We extracted the included studies, assessed their quality, and estimated pooled risks by time after infection and according to disease severity.
RESULTS: Risks were highest in the acute phase [PE: 27.1 (17.8-41.10); MI: 4.4 (1.6-12.4); stroke: 3.3 (2.1-5.2); IS: 5.6 (2.1-14.8); HS: 4.0 (0.1-326.2)] compared to the post-acute phase [PE: 2.9 (2.6-3.3); MI: 1.4 (1.1-1.9); stroke: 1.4 (1.0-2.0); IS: 1.6 (0.9-2.7)]. Highest risks were observed after infection confirmation, dropping during the first month post-infection (e.g. PE: RR(7 days) = 31; RR(1 month) = 8.1). A doubled risk was still observed until 4.5 months for PE, one month for MI and two months for IS. Risks decreased with decreasing disease severity.
CONCLUSIONS: Because of increased risk of CVD outcomes, management of persons who survived a severe SARS-CoV-2 infection is required, especially during the first nine months post-infection.

Acute ST-elevation myocardial infarction (STEMI) and acute ischaemic stroke (AIS) share a number of similarities. However, important differences in pathophysiology demand a disease-tailored approach. In both conditions, fast treatment plays a crucial role as ischaemia and eventually infarction develop rapidly. Furthermore, in both fields, the introduction of fibrinolytic treatments historically preceded the implementation of endovascular techniques. However, in contrast to STEMI, only a minority of AIS patients will eventually be considered eligible for reperfusion treatment. Non-invasive cerebral imaging always precedes cerebral angiography and thrombectomy, whereas coronary angiography is not routinely preceded by non-invasive cardiac imaging in patients with STEMI. In the late or unknown time window, the presence of specific patterns on brain imaging may help identify AIS patients who benefit most from reperfusion treatment. For STEMI, a uniform time window for reperfusion up to 12 h after symptom onset, based on old placebo-controlled trials, is still recommended in guidelines and generally applied. Bridging fibrinolysis preceding endovascular treatment still remains the mainstay of reperfusion treatment in AIS, while primary percutaneous coronary intervention is the strategy of choice in STEMI. Shortening ischaemic times by fine-tuning collaboration networks between ambulances, community hospitals, and tertiary care hospitals, optimizing bridging fibrinolysis, and reducing ischaemia-reperfusion injury are important topics for further research. The aim of this review is to provide insights into the common as well as diverging pathophysiology behind current reperfusion strategies and to explore new ways to enhance their clinical benefit.

Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that systemic infection such as herpes zoster (HZ) / ophthalmicus herpes zoster (HZO) can potentially trigger stroke. This study includes an updated systematic review and meta-analysis of the epidemiologic data on the connection between HZ/HZO infection and the risk of stroke. A meticulous search of different database yielded 905 studies. Furthermore, an additional 14 studies from a previous meta-analysis were incorporated. Eligible studies underwent rigorous screening, resulting in 18 papers. Statistical analyses, including random/fixed effects models and subgroup analyses, were conducted to assess pooled relative risk (RR) and heterogeneity. The meta-analysis consisted of 5,505,885 participants and found a statistically significant association between HZ infection and the risk of stroke (pooled RR = 1.22, 95% confidence interval [CI] 1.12-1.34). The HZO infection showed a significantly higher overall pooled RR of 1.71 (95% CI 1.06-2.75), indicating a strong connection with the risk of stroke. Subgroup analysis revealed that the odds ratio might play a significant role in causing heterogeneity. Time since infection emerged as a crucial factor, with heightened stroke risk in the initial year post-HZ/HZO exposure, followed by a decline after the first year. Asian/Non-Asian studies demonstrated varied results in HZ/HZO patients. Meta-analysis reveals a significant HZ/HZO-stroke link. Subgroups highlight varied risks and warrant extended Asian/non-Asian patient investigation.

BACKGROUND: The World Health Organisation has expanded the definition of stroke to include people with symptoms less than 24 h if they have evidence of stroke on neuroimaging. The impact is that people previously diagnosed as having a transient ischaemic attack (TIA) would now be considered to have had a stroke. This change will impact incidence and outcomes of stroke and increase eligibility for secondary prevention. We aimed to evaluate the new ICD-11 criteria retrospectively to previous TIA studies to understand the change in incidence and outcomes of this type of stroke.
METHODS: We conducted a systematic review of observational studies of the incidence and outcomes of clinically defined TIA. We searched PubMed, EMBASE, and Google Scholar from inception to 23rd May 2023. Study quality was assessed using a risk of bias tool for prevalence studies.
RESULTS: Our review included 25 studies. The rate of scan positivity for stroke among those with clinically defined TIA was 24 %, (95 % CI, 16-33 %) but with high heterogeneity (I2 = 100 %, p <0.001). Sensitivity analyses provided evidence that heterogeneity could be explained by methodology and recruitment method. The scan positive rate when examining only studies at low risk of bias was substantially lower, at 13 % (95 % CI, 11-15 %, I2 = 0, p = 0.77). We estimate from population-based incidence studies that ICD-11 would result in an increase stroke incidence between 4.8 and 10.5 per 100,000 persons/year. Of those with DWI-MRI evidence of stroke, 6 % (95 % CI, 3-11 %) developed a recurrent stroke in the subsequent 90 days, but with substantial heterogeneity (I2 = 67 %, p = 0.02).
CONCLUSIONS: The impact of the ICD-11 change in stroke definition on incidence and outcomes may have been overestimated by individual studies. Community-based stroke services with access to DWI MRI are likely to accurately diagnose greater numbers of people with mild ICD-11 stroke, increasing access to effective prevention.

Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association using prospective stroke data from the Norfolk and Norwich Stroke and TIA Register. Consecutive AIS patients aged ≥40 years admitted December 2003-December 2016 were included. Outcomes: In-hospital mortality, poor discharge, functional outcome (modified Rankin score 3-6), prolonged length of stay (PLoS) > 4 days, and long-term mortality. Restricted cubic spline regressions investigated the albumin-outcome relationship. We updated a systematic review (PubMed, Scopus, and Embase databases, January 2020-June 2023) and undertook a meta-analysis. A total of 9979 patients were included; mean age (standard deviation) = 78.3 (11.2) years; mean serum albumin 36.69 g/L (5.38). Compared to the cohort median, albumin < 37 g/L associated with up to two-fold higher long-term mortality (HRmax; 95% CI = 2.01; 1.61-2.49) and in-hospital mortality (RRmax; 95% CI = 1.48; 1.21-1.80). Albumin > 44 g/L associated with up to 12% higher long-term mortality (HRmax1.12; 1.06-1.19). Nine studies met our inclusion criteria totalling 23,597 patients. Low albumin associated with increased risk of long-term mortality (two studies; relative risk 1.57 (95% CI 1.11-2.22; I2 = 81.28)), as did low-normal albumin (RR 1.10 (95% CI 1.01-1.20; I2 = 0.00)). Strong evidence indicates increased long-term mortality in AIS patients with low or low-normal albumin on admission.

Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.

UNASSIGNED: Cerebral ischaemic stroke is a common disease that poses a serious threat to human health. Butyrate is an important metabolite of intestinal microorganisms. Recent studies have shown that butyrate has a significant protective effect in animal models of cerebral ischaemic injury.
UNASSIGNED: The aim of this study was to evaluate the protective effect of butyrate on cerebral ischaemic stroke by meta-analysis, aiming to provide a scientific basis for the clinical application of butyrate in patients with cerebral ischaemia.
UNASSIGNED: A systematic search was conducted for all relevant studies published before 23 January 2024, in PubMed, Web of Science, Cochrane Library, and Embase. Methodological quality was assessed using Syrcle\'s risk of bias tool for animal studies. Data were analysed using Rev Man 5.3 software.
UNASSIGNED: A total of nine studies were included, and compared with controls, butyrate significantly increased BDNF levels in the brain (SMD = 2.33, 95%CI = [1.20, 3.47], p < 0.005) and P-Akt expression (SMD = 3.53, 95% CI = [0.97, 6.10], p < 0.05). Butyrate also decreased IL-β levels in the brain (SMD = -2.02, 95% CI = [-3.22, -0.81], p < 0.005), TNF-α levels (SMD = -0.86, 95% CI = [-1.60, -0.12], p < 0.05), and peripheral vascular IL-1β levels (SMD = -2.10, 95%CI = [-3.59, -0.61], p < 0.05). In addition, butyrate reduced cerebral infarct volume (MD = -11.29, 95%CI = [-17.03, -5.54], p < 0.05), mNSS score (MD = -2.86, 95%CI = [-4.12, -1.60], p < 0.005), foot fault score (MD = -7.59, 95%CI = [-9.83, -5, 35], p < 0.005), and Morris water maze time (SMD = -2.49, 95%CI = [-4.42, -0.55], p < 0.05).
UNASSIGNED: The results of this study indicate that butyrate has a protective effect on cerebral ischaemic stroke in animal models, and the mechanism is related to reducing inflammation and inhibiting apoptosis. It provides an evidence-based basis for the future clinical development of butyrate in the treatment of ischaemic stroke.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, CRD42023482844.