Ferroptosis mediated by TNFSF9 interferes in acute ischaemic stroke reperfusion injury with the progression of acute ischaemic stroke.

In this study, we investigated the potential involvement of TNFSF9 in reperfusion injury associated with ferroptosis in acute ischaemic stroke patients, mouse models and BV2 microglia. We first examined TNFSF9 changes in peripheral blood from stroke patients with successful reperfusion, and constructed oxygen-glucose deprivation-reperfusion (OGD-R) on BV2 microglia, oxygen-glucose deprivation for 6 h followed by reoxygenation and re-glucose for 24 h, and appropriate over-expression or knockdown of TNFSF9 manipulation on BV2 cells and found that in the case of BV2 cells encountering OGD-R over-expression of TNFSF9 resulted in increased BV2 apoptosis. Still, the knockdown of TNFSF9 ameliorated apoptosis and ferroptosis. In an in vivo experiment, we constructed TNFSF9 over-expression or knockout mice by intracerebral injection of TNFSF9-OE or sh-TNFSF9 adenovirus. We performed the middle cerebral artery occlusion (MCAO) model on day four, 24 h after ligation of the proximal artery, for half an hour to recanalize. As luck would have it, over-expression of TNFSF9 resulted in increased brain infarct volumes, neurological function scores and abnormalities in TNFSF9-related TRAF1 and ferroptosis-related pathways, but knockdown of TNFSF9 improved brain infarcts in mice as well as reversing TNFSF9-related signalling pathways. In conclusion, our data provide the first evidence that TNFSF9 triggers microglia activation by activating the ferroptosis signalling pathway following ischaemic stroke, leading to brain injury and neurological deficits.

Lower serum uric acid to serum creatinine ratio as a predictor of poor functional outcome after mechanical thrombectomy in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT-treated AIS patients. METHODS: Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death. RESULTS: Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score (ρ = -0.095, p = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282-0.428, p < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724-0.788, p < 0.001). CONCLUSION: The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90-day functional outcome in AIS patients undergoing MT.

Efficacy and safety of hyperbaric oxygen therapy in acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of adjunctive hyperbaric oxygen therapy (HBOT) in acute ischaemic stroke (AIS) based on existing evidence. METHODS: We conducted a comprehensive search through April 15, 2023, of seven major databases for randomized controlled trials (RCTs) comparing adjunctive hyperbaric HBOT with non-HBOT (no HBOT or sham HBOT) treatments for AIS. Data extraction and assessment were independently performed by two researchers. The quality of included studies was evaluated using the tool provided by the Cochrane Collaboration. Meta-analysis was conducted using Rev Man 5.3. RESULTS: A total of 8 studies involving 493 patients were included. The meta-analysis showed no statistically significant differences between HBOT and the control group in terms of NIHSS score (MD = -1.41, 95%CI = -7.41 to 4.58), Barthel index (MD = 8.85, 95%CI = -5.84 to 23.54), TNF-α (MD = -5.78, 95%CI = -19.93 to 8.36), sICAM (MD = -308.47, 95%CI = -844.13 to 13227.19), sVCAM (MD = -122.84, 95%CI = -728.26 to 482.58), sE-selectin (MD = 0.11, 95%CI = -21.86 to 22.08), CRP (MD = -5.76, 95%CI = -15.02 to 3.51), adverse event incidence within ≤ 6 months of follow-up (OR = 0.98, 95%CI = 0.25 to 3.79). However, HBOT showed significant improvement in modified Rankin score (MD = 0.10, 95%CI = 0.03 to 0.17), and adverse event incidence at the end of treatment (OR = 0.42, 95%CI = 0.19 to 0.94) compared to the control group. CONCLUSION: While our findings do not support the routine use of HBOT for improving clinical outcomes in AIS, further research is needed to explore its potential efficacy within specific therapeutic windows and for different cerebral occlusion scenarios. Therefore, the possibility of HBOT offering clinical benefits for AIS cannot be entirely ruled out.

The individual and combined impacts of pre-existing diabetes and dementia on ischemic stroke outcomes: a registry-based cohort study.

BACKGROUND: Individually, diabetes mellitus and dementia are associated with poorer outcomes after stroke. However, the combined impact of these pre-existing factors on acute ischemic stroke (AIS) outcomes has not been examined. METHODS: All consecutive patients with AIS admitted to Norfolk and Norwich University Hospitals between 2003 and 2016 (catchment population ~ 900,000) were divided into four groups: those with neither diabetes nor dementia (reference), with diabetes without dementia, with dementia without diabetes, and with both co-morbidities. In-hospital mortality, length of hospital stay (LoS), and disability outcomes were analysed using logistic regressions. Post-discharge mortality and recurrence were assessed using Cox regressions. Additionally, interaction terms were added to the models for the short-term outcomes and long-term mortality to test for synergistic effects of diabetes and dementia. Models were adjusted for age, sex, Oxfordshire Community Stroke Project classification, comorbidities, hematological and biochemical measures, and antithrombotic medications. RESULTS: The cohort was 10,812 patients with 52% females and a median age of 80. The median follow-up was 3.8 years for stroke recurrence and 5.5 years for mortality. No significant differences between the four groups existed for in-hospital mortality and post-stroke disability. Patients with dementia had significantly longer LoS (OR 2.25 [95% CI: 1.34-3.77] and 1.31 [1.02-1.68] with and without diabetes, respectively). Patients with both comorbidities had the highest risk of stroke recurrence (HR 2.06 [1.12-3.77]), followed by those with only dementia (1.59 [1.15-2.20]) and only diabetes (1.25 [1.06-1.49]). Similarly, the patient group with both diabetes and dementia had the highest long-term mortality risk (1.76 [1.33-2.37]). The hazard ratios for patients with only dementia and only diabetes were 1.71 [1.46-2.01] and 1.19 [1.08-1.32], respectively. No significant interactions were seen between diabetes and dementia with regards to their effects on the outcomes. CONCLUSION: Individual and cumulative impacts of the two conditions on long-term mortality and stroke recurrence were notable. However, no synergistic impact of the two comorbidities were seen on the stroke outcomes tested in our study. Therefore, tailoring the management of stroke patients based on additional requirements associated with each pre-existing condition will be more impactful towards improving outcomes.

Pressure ulcer development in patients treated for acute ischaemic stroke.

OBJECTIVE: The aim of this study was to determine the incidence of pressure ulcers (PUs) in patients treated for acute ischaemic stroke (AIS) and to evaluate comorbid/confounding factors. METHOD: The study included patients treated for AIS who were divided into three treatment groups: those receiving intravenous tissue plasminogen activator therapy (tPA); patients receiving mechanical thrombectomy (MT); and those receiving both tPA and MT. PUs were classified according to the international classification system and factors that may influence their development were investigated. RESULTS: A total of 242 patients were included in this study. The incidence of PUs in patients treated for AIS was 7.4%. Most PUs were located on the sacrum (3.7%), followed by the gluteus (3.3%) and trochanter (2.9%). With regards to PU classification: 29% were stage I; 34% were stage II; and the remainder were stage III. Age was not a significant factor in the development of PUs (p=0.172). Patients in the tPA group had a lower PU incidence (2.3%) than patients in the tPA+MT group (15.7%) and MT group (12.1%) (p=0.001). Patients with PUs had a longer period of hospitalisation (18.5±11.92 days) than patients without a PU (8.0±8.52 days) (p=0.000). National Institute of Health Stroke Scale (NIHSS) scores at admission were higher in patients with PUs than in patients without a PU (14.33±4.38 versus 11.08±5.68, respectively; p=0.010). The difference in presence of comorbidities between patients with and without PUs (p=0.922) and between treatment groups (p=0.677) were not statistically significant. The incidence of PUs was higher in patients requiring intensive care, but this difference was not statistically significant (p=0.089). CONCLUSION: In this study, patients treated for AIS with high NIHSS scores at admission and/or receiving MT were at higher risk for PUs, and so particular attention should be given to these patients in order to prevent PU development.

Comparison of clinical outcomes between family caregivers and professional caregivers in in-hospital patients with acute ischaemic stroke: A prospective cohort study.

AIM: This study explored the impact of different care modes on the outcome of hospitalized patients with acute ischaemic stroke (AIS) during hospitalization and 3 months after discharge. METHODS: This was a prospective cohort study comparing the outcomes at hospitalization, at discharge, and at 3 months post discharge among AIS patients with different caregiving arrangements from 9, December 2022 to 20, August 2023. The general information questionnaire, Modified Barthel Index, Shortened General Comfort Questionnaire, Perceived Social Support scale, Herth Hope Index, modified Rankin scale and EQ-5D-5L were utilized for the investigation. RESULTS: The psychological evaluation scores during hospitalization, including comfort, perceived social support, and hope, did not significantly differ between the two groups of AIS patients (p > .05). Moreover, there were no significant impacts observed in terms of length of stay (LOS) at the hospital or hospitalization expense (p > .05). The proportion of patients with intact functionality was greater in the family caregiver group 3 months after discharge (16.5%). However, when stratified based on prognosis, the difference in outcomes between the two groups of patients did not reach statistical significance (p > .05). The analysis of ADL, quality of life and stroke recurrence in 276 surviving ischaemic stroke patients 3 months post discharge indicated no differences between the two groups across all three aspects (p > .05). CONCLUSION: Older and divorced or widowed AIS patients tend to prefer professional caregivers. The psychological state during hospitalization, length of hospital stay and hospitalization expenses are not influenced by the caregiving model. Three months post discharge, a greater proportion of patients in the family caregiving group had intact mRS functionality, but this choice did not impact patient prognosis, stroke recurrence, quality of life or independence in ADL.

Adjunctive rescue therapy in acute large vessel occlusion secondary to underlying intracranial atherosclerotic disease.

BACKGROUND: The optimal treatment for patients with acute large vessel occlusion (LVO) secondary to intracranial atherosclerotic disease (ICAD) is unclear. Adjunctive rescue therapy with balloon angioplasty or stenting may be necessary to ensure vessel patency. We aimed to compare the safety and clinical outcomes of adjunctive rescue therapy vs lone thrombectomy for ICAD-related-LVO. METHODS: A retrospective propensity score matching analysis was performed in acute stroke patients who had endovascular thrombectomy between 2008-2021. We included patients with acute ICAD-related-LVO. The location of ICAD and exposure to thrombolysis were used to generate propensity score matching to estimate the likelihood of treatment by adjunctive rescue therapy. The primary clinical outcome (90-day modified rankin scale 0-2) and safety outcomes (symptomatic intracerebral hemorrhage) were assessed between the two groups. RESULTS: One-hundred and forty-four patients were included. The median (IQR) age was 68(59-76) and 52(36%) were females. The baseline NIHSS was 12.5(8-19). Sixty-seven (47%) patients had ICAD in M1 or M2 segments. Forty-six patients (67%) had lone thrombectomy and twenty-one (28%) had adjunctive rescue therapy. Propensity score matching did not demonstrate significant differences in 90-day modified Rankin Score 0-2 between lone thrombectomy (38.8%) and adjunctive rescue therapy (39.3%) (p=0.3). Lone thrombectomy, compared to adjunctive rescue therapy, did not result in significantly more symptomatic intracerebral hemorrhages (2.8% vs 8.3%, p=0.6), nor progressive occlusion (17% vs 19%, p=0.8). CONCLUSION: We did not find significant differences in clinical outcomes and safety between lone thrombectomy and adjunctive rescue therapy. Randomized controlled studies are required to resolve the equipoise in treatment of ICAD-related-LVO.

Mechanical thrombectomy in very elderly people: shortand long-term outcomes of endovascular stroke treatment in nonagenarians.

AIM OF STUDY: To assess outcomes of mechanical thrombectomy (MT) in nonagenarians suffering from acute ischaemic stroke (AIS) in a 1-year follow-up. CLINICAL RATIONALE FOR STUDY: Age is a factor associated with both the occurrence of AIS and a poorer prognosis. As the population ages, the prevalence of AIS among the very old (90 and older) is expected to rise. Data on long-term outcomes of MT, being the optimal treatment of AIS caused by large vessel occlusions, is scarce in the population of nonagenarians. MATERIAL AND METHODS: We analysed all AIS patients treated with MT in a single Comprehensive Stroke Centre. We compared two subgroups: nonagenarians (people aged 90-99) and controls ( < 90 years) in terms of cardiovascular risk factors profile, stroke severity, treatment course, presence of in-hospital complications, and outcomes (mortality and good functional outcome defined as modified Rankin Scale ≤ 2) at discharge and at 90- and 365-day follow-ups. RESULTS: Nonagenarians were more commonly female and suffering from atrial fibrillation. They more often developed urinary tract infection during hospitalisation. Stroke severity, treatment course and in-hospital outcomes were comparable between the groups. Nonagenarians had non-significantly higher 90-day and 365-day mortality, and a significantly lower rate of good functional outcomes after 90 days (25.0% vs 57.7%, p = 0.011) and 365 days (31.5% vs 61.0%, p = 0.020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Despite worse outcomes than in younger patients, 25% of nonagenarians were functionally independent three months after MT, and almost one in three of them were so a year after the procedure, thereby showing the benefits of the treatment in this group.

Predictors of good functional outcome in ischaemic stroke patients without delayed neurological improvement after mechanical thrombectomy.

INTRODUCTION: This study aimed to identify predictors of 90-day good functional outcome (GFO) in patients with acute ischaemic stroke (AIS) who were treated with mechanical thrombectomy but did not achieve a delayed neurological improvement (DNI). CLINICAL RATIONALE FOR THE STUDY: In-hospital neurological improvement in patients with AIS is consistently associated with long- -term GFO. Patients who experience neither early nor delayed neurological improvement can still achieve long-term GFO, but predictors of such an outcome have not been studied. MATERIAL AND METHODS: This single-centre retrospective study involved 307 patients with anterior circulation AIS treated with mechanical thrombectomy. Multiple clinical, biochemical, radiological, and treatment-related variables were collected and analysed. DNI on day 7 was defined as at least a 10-point reduction in the National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score < 2. GFO on day 90 was defined as a modified Rankin Scale (mRS) score ≤ 2. We compared the characteristics of patients with and without DNI, with special attention paid to patients who achieved 90-GFO despite a lack of DNI. Multivariate analyses were then performed to establish independent predictors of 90-day GFO among patients without DNI. RESULTS: DNI occurred in 150 out of 307 patients (48.7%) and significantly increased the odds for 90-day GFO (odds ratio [OR]: 13.99; p < 0.001). Among patients without DNI, 41.4% achieved 90-day GFO. Younger age (OR: 0.96; 95% confidence interval [CI]: 0.93-0.99; p = 0.008), lower baseline NIHSS score (OR: 0.80; 95% CI: 0.73-0.89; p < 0.001), treatment with intravenous thrombolysis (OR: 3.06; 95% CI: 1.25-7.49; p = 0.014), lack of an undetermined aetiology (OR: 0.40; 95% CI: 0.16-0.998; p = 0.050), lack of pneumonia (OR: 0.08; 95% CI: 0.02-0.31; p < 0.001), and higher haemoglobin concentration on admission (OR: 1.31; 95% CI: 1.04-1.69; p = 0.024) were identified as predictors of 90-day GFO in this subgroup. CONCLUSION: Almost half of patients with AIS in anterior circulation treated with mechanical thrombectomy experience DNI, which is a good predictor of 90-day GFO. Furthermore, 40% of patients without DNI achieve 90-day GFO which can be independently predicted by younger age, lower baseline NIHSS score, treatment with intravenous thrombolysis, higher haemoglobin concentration on admission, lack of undetermined ischaemic stroke aetiology, and lack of pneumonia.

Correlation Between Optical Coherence Tomography Angiography Findings at 3 to 6 Weeks and Functional Outcome at 3 Months Following Acute Ischaemic Stroke Due to Extracranial Carotid Artery Atherosclerotic Disease.

We wanted to evaluate if optical coherence tomography angiography OCTA findings could predict the functional outcome in extracranial carotid artery atherosclerotic disease (ECAD) associated stroke. This exploratory study was performed on adults with acute ischaemic stroke due to ECAD at 3-6 weeks following stroke onset with risk factor matched controls without carotid artery stenosis. Twenty-three stroke patients (cases) and 23 controls were enrolled. There was significant difference between cases and controls in deep vessel density at the macula (p = .0007) and in radial peripapillary capillary perfusion density (RPCPD) at the optic nerve head (ONH) (p = .0007). Statistically significant difference was noted in the total superficial vessel density (SVD) at the macula (SVD within 1 standard deviation [SD] versus SVD beyond 1 SD of control data) in the ipsilateral eye and functional outcome at 3 months (poor versus very good outcome, modified Rankin scale [mRS] 0-1 versus mRS 2-6, respectively; p = .0361). There was statistically insignificant correlation between the RPCPD at the ONH and the National Institutes of Health Stroke Scale score at admission, mRS at discharge, and mRS at 3 months following stroke onset (r = .33, r = .35, r = .39; p = .11, p = .09, p = .06, respectively). The findings of this exploratory study suggested that OCTA findings may predict 3 month outcomes in cases of ECAD-related stroke and could be useful in decision making in future intervention studies as to whether intervene or not in patients having critical or non-critical ECAD for preventing stroke.

Temporal trends and outcomes in acute ischaemic stroke patients with a current or historical diagnosis of cancer.

BACKGROUND AND PURPOSE: The aim was to evaluate the temporal trends, characteristics and in-hospital outcomes of patients hospitalized with acute ischaemic stroke (AIS) between those with and without current or historical malignancies. METHODS: Adult hospitalizations with a primary diagnosis of AIS were identified from the National Inpatient Sample database 2007-2017. Logistic regression was used to compare the differences in the utilization of AIS interventions and in-hospital outcomes. For further analysis, subgroup analyses were performed stratified by cancer subtypes. RESULTS: There were 892,862 hospitalizations due to AIS, of which 108,357 (12.14%) had a concurrent diagnosis of current cancer (3.41%) or historical cancer (8.72%). After adjustment for confounders, patients with current malignancy were more likely to have worse clinical outcomes. The presence of historical cancers was not associated with an increase in poor clinical outcomes. Additionally, AIS patients with current malignancy were less likely to receive intravenous thrombolysis (adjusted odds ratio 0.66, 95% confidence interval 0.63-0.71). Amongst the subgroups of AIS patients treated with intravenous thrombolysis or mechanical thrombectomy, outcomes varied by cancer types. Notably, despite these acute stroke interventions, outcome remains poor in AIS patients with lung cancer. CONCLUSIONS: Although AIS patients with malignancy generally have worse in-hospital outcomes versus those without, there were considerable variations in these outcomes according to different cancer types and the use of AIS interventions. Finally, treatment of these AIS patients with a current or historical cancer diagnosis should be individualized.

Trimethylamine N-oxide predicts stroke severity in diabetic patients with acute ischaemic stroke and is related to glycemic variability.

BACKGROUND AND PURPOSE: The present study analyzed the relationship between circulating trimethylamine N-oxide (TMAO) levels and stroke severity in diabetic patients with acute ischaemic stroke. A further aim was to investigate whether higher TMAO levels were associated with platelet aggregation and glycemic variability. METHODS: This was a cross-sectional analysis of 108 patients with type 2 diabetes mellitus (DM) undergoing acute ischaemic stroke and 60 healthy controls. Fasting plasma TMAO was measured using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. RESULTS: Plasma TMAO levels of patients with acute ischaemic stroke were significantly higher than those of healthy controls. Amongst stroke patients, 50 were defined as undergoing mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke. Platelet aggregation and mean amplitude of glycemic excursions were both correlated with plasma TMAO levels and these relationships remained significant in multiple linear regression analyses. Moreover, in streptozotocin-induced diabetic rats fed a diet enriched with choline to increase TMAO synthesis, platelet aggregation was significantly increased in the DM + choline and fluctuating DM (FDM) + choline groups compared to the control group. This increase was abolished in rats receiving oral antibiotics, which markedly reduced plasma TMAO levels. Importantly, compared with the DM + choline group, the FDM + choline group displayed significantly elevated TMAO levels and higher platelet aggregation. CONCLUSIONS: Our results demonstrated that higher plasma TMAO levels were associated with stroke severity and suggested a novel link between plasma TMAO levels and glycemic variability in diabetic patients with acute ischaemic stroke.

Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.

Prognostic significance of 24-h blood pressure and variability indices in the outcome of acute ischaemic stroke.

BACKGROUND: The association between blood pressure (BP) levels and BP variability (BPV) following acute ischaemic stroke (AIS) and outcome remains controversial. AIMS: To investigate the predictive value of systolic BP (SBP) and diastolic BP (DBP) and BPV measured using 24-h ambulatory blood pressure monitoring (ABPM) methods during AIS regarding outcome. METHODS: A total of 228 AIS patients (175 without prior disability) underwent ABPM every 20 min within 48 h from onset using an automated oscillometric device (TM 2430, A&D Company Ltd) during day time (7:00-22:59) and night time (23:00-6:59). Risk factors, stroke subtypes, clinical and laboratory findings were recorded. Mean BP parameters and several BPV indices were calculated. End-points were death and unfavourable functional outcome (disability/death) at 3 months. RESULTS: A total of 61 (26.7%) patients eventually died. Multivariate logistic regression analysis revealed that only mean night-time DBP (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.00-1.07) was an independent prognostic factor of death. Of the 175 patients without prior disability, 79 (45.1%) finally met the end-point of unfavourable functional outcome. Mean 24-h SBP (HR: 1.03; 95% CI: 1.00-1.05), day-time SBP (HR: 1.02; 95% CI: 1.00-1.05) and night-time SBP (HR: 1.03; 95% CI: 1.01-1.05), SBP nocturnal decline (HR: 0.93; 95% CI: 0.88-0.99), mean 24-h DBP (HR: 1.08; 95% CI: 1.03-1.13), day-time DBP (HR: 1.07; 95% CI: 1.03-1.12) and night-time DBP (HR: 1.06; 95% CI: 1.02-1.10) were independent prognostic factors of an unfavourable functional outcome. CONCLUSIONS: In contrast with BPV indices, ABPM-derived BP levels and lower or absence of BP nocturnal decline in the acute phase are prognostic factors of outcome in AIS patients.

Prevalence of myocardial injury in patients after acute ischaemic stroke according to standard criteria.

This study examined the prevalence of acute and chronic myocardial injury according to standard criteria in patients after acute ischaemic stroke (AIS) and its relation to stroke severity and short-term prognosis. Between August 2020 and August 2022, 217 consecutive patients with AIS were enrolled. Plasma levels of high-sensitive cardiac troponin I (hs-cTnI) were measured in blood samples obtained at the time of admission and 24 and 48 h later. The patients were divided into three groups according to the Fourth Universal Definition of Myocardial Infarction: no injury, chronic injury, and acute injury. Twelve-lead ECGs were obtained at the time of admission, 24 and 48 h later, and on the day of hospital discharge. A standard echocardiographic examination was performed within the first 7 days of hospitalization in patients with suspected abnormalities of left ventricular function and regional wall motion. Demographic characteristics, clinical data, functional outcomes, and all-cause mortality were compared between the three groups. The National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following hospital discharge were used to assess stroke severity and outcome. Elevated hs-cTnI levels were measured in 59 patients (27.2%): 34 patients (15.7%) had acute myocardial injury and 25 patients (11.5%) had chronic myocardial injury within the acute phase after ischaemic stroke. An unfavourable outcome, evaluated based on the mRS at 90 days, was associated with both acute and chronic myocardial injury. Myocardial injury was also strongly associated with all-cause death, with the strongest association in patients with acute myocardial injury, at 30 days and at 90 days. Kaplan-Meier survival curves showed that all-cause mortality was significantly higher in patients with acute and chronic myocardial injury than in patients without myocardial injury (P < 0.001). Stroke severity, evaluated with the NIHSS, was also associated with acute and chronic myocardial injury. A comparison of the ECG findings between patients with and without myocardial injury showed a higher occurrence in the former of T-wave inversion, ST segment depression, and QTc prolongation. In echocardiographic analysis, a new abnormality in regional wall motion of the left ventricle was identified in six patients. Chronic and acute myocardial injury with hs-cTnI elevation after AIS are associated with stroke severity, unfavourable functional outcome, and short-term mortality.

Factors associated with delay to carotid endarterectomy for acute ischaemic stroke in South Australia: A multicentre retrospective cohort study.

BACKGROUND: The greatest benefits of carotid endarterectomy (CEA) accrue when performed within two weeks of acute ischaemic stroke (AIS) due to symptomatic carotid stenosis. Previous studies have identified multiple factors contributing to CEA delay. AIMS: To determine factors associated with delayed CEA in patients admitted to tertiary stroke centres within a major metropolitan region with AIS METHODS: In a retrospective cohort study, consecutive patients admitted to the tertiary hospitals with stroke units within South Australia (Lyell McEwin Hospital, Royal Adelaide Hospital and Flinders Medical Centre) between 2016 to 2020 were included. Univariable and multivariable logistic regression were used to identify individual factors associated with time from symptom onset to CEA of over two weeks. RESULTS: A total of 174 patients were included. The median time to CEA was 5 days (IQR 3-9.75). Delayed CEA beyond 14 days occurred in 28/174 (16%). Factors most associated with delayed CEA included presentation to a tertiary hospital without onsite Vascular Surgical Unit (OR 3.71, 95%CI 1.31-10.58), history of previous stroke (OR 3.38, 95% CI 1.11-9.84) and presenting NIHSS above 6 (OR 5.16, 95% CI 1.60-16.39). CONCLUSION: This study identified that presentation to a tertiary hospital without a Vascular Surgery Unit, history of previous stroke and presenting NIHSS above 6 were associated with delay to CEA in AIS patients in South Australia. Interventional studies aiming to improve the proportion of patients that receive CEA within 14 days are required.

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke - a single centre experience.

INTRODUCTION: Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS). CLINICAL RATIONALE FOR THE STUDY: New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment. MATERIAL AND METHODS: Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0-2 points at discharge. RESULTS: This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0-2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

BACKGROUND AND PURPOSE: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice. METHODS: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared. RESULTS: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORadjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted  = 1.75, p = 0.002; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.52, p = 0.005; death: ORadjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (padjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORadjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted  = 1.80, p = 0.001; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.38, p < 0.0001; death: ORadjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORadjusted  = 0.58, p = 0.004; death: ORadjusted  = 1.57, p = 0.014; mRS shift: padjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped. CONCLUSIONS: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Prognostic significance of the clinical and radiological haemorrhagic transformation subtypes in acute ischaemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to investigate the associations of haemorrhagic transformation (HT) and its clinical and radiological subtypes with functional outcome, mortality, early neurological deterioration (END) and neurological complications in patients with acute ischaemic stroke (AIS). METHODS: A systematic review and meta-analysis of observational studies on the associations of overall HT, clinical HT subtypes (asymptomatic intracerebral haemorrhage [aICH] and symptomatic intracerebral haemorrhage [sICH]) or radiological HT subtypes (haemorrhagic infarction [HI-1 or HI-2] and parenchymal haemorrhage [PH-1 or PH-2]) with prognosis in patients with AIS was performed. PubMed, Web of Science and Embase were systematically searched. Random effects models were used to calculate pooled estimates. RESULTS: Fifty-one studies with 100,510 patients were pooled in the meta-analysis. Overall HT was associated with worse functional outcome (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.55-2.90), increased mortality (OR 1.87, 95% CI 1.52-2.30), END (OR 2.35, 95% CI 1.46-3.77), early-onset seizures (OR 2.58, 95% CI 1.63-4.10) and post-stroke epilepsy (OR 2.23, 95% CI 1.11-4.49). For clinical subtypes, sICH remained significantly associated with the aforementioned poor prognoses except post-stroke epilepsy, and aICH was associated with worse functional outcome but was unrelated to mortality. For radiological subtypes, PH (especially PH-2) was strongly associated with poor prognosis. HI-2 was associated with worse functional outcome, and HI-1 was associated with a lower risk of mortality and END. CONCLUSIONS: Regardless of whether AIS patients undergo thrombolysis or thrombectomy, overall HT, sICH and PH (especially PH-2) are associated with a substantially increased risk of worse functional outcome, mortality, END or neurological complications. The presence of aICH is related to worse functional outcome but is independent of increased mortality. HI-2 impairs functional independence, and HI-1 does not cause neurological impairment.

Effect of Sex on Outcomes of Mechanical Thrombectomy in Basilar Artery Occlusion: A Multicentre Cohort Study.

INTRODUCTION: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. METHODS: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). RESULTS: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. CONCLUSION: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.