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Introduction The benefit of additional reperfusion attempts in patients with partial angiographic reperfusion (TICI2b) is unknown. The PROCEED model predicts subsequent favorable occurrence of complete reperfusion (i.e. delayed reperfusion [DR]) at 24 hours after initial incomplete angiographic reperfusion at the conclusion of thrombectomy. This study aims to externally validate the PROCEED model using pooled data from multiple international trials that systematically performed follow‐up perfusion imaging. Methods Individual patient data for external validation were obtained from the EXTEND‐IA, EXTEND‐IA TNK part 1 and 2 trials (clinicaltrials.gov, unique‐identifier: NCT01492725, NCT02388061 and NCT03340493). The model’s primary outcome of interest was the occurrence of DR, defined as the absence of any focal perfusion deficit on follow‐up CT or MRI perfusion imaging maps, despite initial incomplete angiographic reperfusion on the final thrombectomy angiography series. The updated model’s performance was evaluated with discrimination, calibration and clinical decision curves. Results We analyzed 267 patients for the external validation, with median age of 74 (IQR 64 – 80), 44.2% were female and 62% had DR. The externally validated model had good discrimination (C‐statistic 0.81, 95% CI 0.72 – 0.86) and was well calibrated (intercept 0.22, 95% CI 0.18‐0.33 and slope 0.96, 95% CI 0.81‐1.23). With threshold probability of R=12% (i.e. 88% chance of having DR), pursuing additional reperfusion attempts to pursue complete angiographic reperfusion in a patient with high‐likelihood of DR were seven times worse (Cost:Benefit Ratio 1:7, Figure 1) than no further endovascular maneuver. In terms of standardized net reduction, the PROCEED model could reduce one in five unnecessary interventions without missing an intervention for any patient who would eventually have DR. Across a wide range of threshold probabilities, the model outperformed the scenario of the typical decision‐making process in the angiography suite, based on the current treatment guidelines. Conclusion The externally validated model had good predictive accuracy and discrimination. Depending on the acceptable risk threshold, the model may compliment clinical judgment of the treating physicians and inform on natural progression of untreated incomplete reperfusion.

BackgroundHemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].MethodsElectronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated.ResultsA total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT.ConclusionSeveral predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P

Background and PurposeCerebral venous systems play a key role in regulating stroke outcomes. We aimed to elucidate the effect of the transverse sinus (TS) filling patterns on edema expansion and neurological outcomes in patients with acute large artery occlusion (LAO).Materials and MethodsWe recruited consecutive patients with acute M1 middle cerebral artery and/or internal carotid artery occlusion who underwent pretreatment computed tomographic perfusion (CTP). On the reconstructed 4-dimensional computed tomographic angiography derived from CTP, the filling defect of the ipsilateral transverse sinus (FDITS) was defined as the length of contrast filling defect occupying at least half of the ipsilateral TS. An unfavorable outcome was defined as having a modified Rankin Scale (mRS) score of 3–6 at 3 months.ResultsA total of 318 patients were enrolled in the final analysis and 70 (22.0%) patients had baseline FDITS. The presence of FDITS was associated with the baseline NIHSS (odds ratio [OR] 1.119; 95% CI, 1.051–1.192; p < 0.001) and poor arterial collaterals (OR 3.665; 95% CI 1.730–7.766; p = 0.001). In addition, FDITS was associated with 24-h brain edema expansion (OR 7.188; 95% CI, 3.095–16.696; p < 0.001) and 3-month unfavorable outcome (OR 8.143; 95% CI 2.547–26.041; p < 0.001) independent of arterial collateral status. In the subgroup analysis of patients with FDITS who received reperfusion therapy, no significant difference was found in the rate of edema expansion and unfavorable outcome between non-reperfusion and reperfusion subgroups (both p > 0.05).ConclusionFilling defect of the ipsilateral transverse sinus was associated with edema expansion and an unfavorable outcome irrespective of the baseline arterial collateral status in patients with acute LAO, indicating that FDITS may be an important stroke-related prognostic imaging marker.

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic.Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic.Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67–0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88–0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65–0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73–0.83)Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

Background: To compare the cost-effectiveness of providing endovascular thrombectomy (EVT) for patients with ischemic stroke in the >4.5 h time window between patient groups who met and did not meet the perfusion imaging trial criteria.Methods: A discrete event simulation (DES) model was developed to simulate the long-term outcome post EVT in patients meeting or not meeting the extended time window clinical trial perfusion imaging criteria at presentation, vs. medical treatment alone (including intravenous thrombolysis). The effectiveness of thrombectomy in patients meeting the landmark trial criteria (DEFUSE 3 and DAWN) was derived from a prospective cohort study of Australian patients who received EVT for ischemic stroke, between 2015 and 2019, in the extended time window (>4.5 h).Results: Endovascular thrombectomy was shown to be a cost-effective treatment for patients satisfying the clinical trial criteria in our prospective cohort [incremental cost-effectiveness ratio (ICER) of $11,608/quality-adjusted life year (QALY) for DEFUSE 3-postive or $34,416/QALY for DAWN-positive]. However, offering EVT to patients outside of clinical trial criteria was associated with reduced benefit (−1.02 QALY for DEFUSE 3; −1.43 QALY for DAWN) and higher long-term patient costs ($8,955 for DEFUSE 3; $9,271 for DAWN), thereby making it unlikely to be cost-effective in Australia.Conclusions: Treating patients not meeting the DAWN or DEFUSE 3 clinical trial criteria in the extended time window for EVT was associated with less gain in QALYs and higher cost. Caution should be exercised when considering this procedure for patients not satisfying the trial perfusion imaging criteria for EVT.

In the present study we sought to measure the relative statistical value of various multimodal CT protocols at identifying treatment responsiveness in patients being considered for thrombolysis. We used a prospectively collected cohort of acute ischemic stroke patients being assessed for IV-alteplase, who had CT-perfusion (CTP) and CT-angiography (CTA) before a treatment decision. Linear regression and receiver operator characteristic curve analysis were performed to measure the prognostic value of models incorporating each imaging modality. One thousand five hundred and sixty-two sub-4.5 h ischemic stroke patients were included in this study. A model including clinical variables, alteplase treatment, and NCCT ASPECTS was weak (R2 0.067, P < 0.001, AUC 0.605) at predicting 90 day mRS. A second model, including dynamic CTA variables (collateral grade, occlusion severity) showed better predictive accuracy for patient outcome (R2 0.381, P < 0.001, AUC 0.781). A third model incorporating CTP variables showed very high predictive accuracy (R2 0.488, P < 0.001, AUC 0.899). Combining all three imaging modalities variables also showed good predictive accuracy for outcome but did not improve on the CTP model (R2 0.439, P < 0.001, AUC 0.825). CT perfusion predicts patient outcomes from alteplase therapy more accurately than models incorporating NCCT and/or CT angiography. This data has implications for artificial intelligence or machine learning models.

Introduction: A telestroke network in Northern New South Wales, Australia has been developed since 2017. We theorized that the telestroke network development would drive a progressive improvement in stroke care metrics over time.Aim: This study aimed to describe changes in acute stroke workflow metrics over time to determine whether they improved with network experience.Methods: We prospectively collected data of patients assessed by telestroke who received multimodal computed tomography (mCT) and were diagnosed with ischemic stroke or transient ischemic attack from January 2017 to July 2019. The period was divided into two phases (phase 1: January 2017 – October 2018 and phase 2: November 2018 – July 2019). We compared median door-to-call, door-to-image, and door-to-decision time between the two phases.Results: We included 433 patients (243 in phase 1 and 190 in phase 2). Each spoke site treated 1.5–5.2 patients per month. There were Door-to-call time (median 39 in phase 1, 35 min in phase 2, p = 0.18), and door-to-decision time (median 81.5 vs. 83 min, p = 0.31) were not improved significantly. Similarly, in the reperfusion therapy subgroup, door-to-call time (median 29 vs. 24.5 min, p = 0.12) and door-to-decision time (median 70.5 vs. 67.5 min, p = 0.75) remained substantially unchanged. Regression analysis showed no association between time in the network and door-to-decision time (coefficient 1.5, p = 0.32).Conclusion: In our telestroke network, acute stroke timing metrics did not improve over time. There is the need for targeted education and training focusing on both stroke reperfusion competencies and the technical aspects of telestroke in areas with limited workforce and high turnover.

Background and Aims: Disability-adjusted life years (DALYs) are an important measure of the global burden of disease that informs patient outcomes and policy decision-making. Our study aimed to compare the DALYs saved by endovascular thrombectomy (EVT) in the Australasian-based EXTEND-IA trial vs. clinical registry data from EVT in Australian routine clinical practice.Methods: The 3-month modified Rankin scale (mRS) outcome and treatment status of consecutively enrolled Australian patients with large vessel occlusion (LVO) stroke were taken from the International Stroke Perfusion Imaging Registry (INSPIRE). DALYs were calculated as the summation of years of life lost (YLL) due to premature death and years lived with a disability (YLD). A generalized linear model (GLM) with gamma family and log link was used to compare the difference in DALYs for patients receiving/not receiving EVT while controlling for key covariates. Ordered logit regression model was utilized to compare the difference in functional outcome at 3 months between the treatment groups. Cox regression analysis was undertaken to compare the difference in survival over an 18-year time horizon. Estimated long-term DALYs saved based on the EXTEND-IA randomized controlled trial (RCT) results were used as the comparator.Results: INSPIRE patients who received EVT treatment only achieved nominally better functional outcomes than the non-EVT group (p = 0.181) at 3 months. There was no significant survival gain from EVT over the first 3 months of stroke in both INSPIRE and EXTEND-IA patients. However, measured against no EVT in the long-term, EVT in INSPIRE was associated with no significant survival gain [hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.78–1.08, p = 0.287] compared with the survival benefit extrapolated from the EXTEND-IA trial (HR: 0.42, 95% CI: 0.22–0.82, p = 0.01]. Offering EVT to patients with LVO stroke was also associated with fewer DALYs lost (11.04, 95% CI: 10.45–11.62) than those not receiving EVT in INSPIRE (12.13, 95% CI: 11.75–12.51), a reduction of −1.09 DALY (95% CI: −1.76 to −0.43, p = 0.002). The absolute magnitude of the treatment effect was lower than that seen in EXTEND-IA (−2.72 DALY reduction in EVT vs non-EVT patients).Conclusions: EVT for the treatment of LVO in a registry of routine care was associated with significantly lower DALYs lost than medical care alone, but the saved DALYs are less than those reported in clinical trials, as there were major differences in the baseline characteristics of the patients.

Background: Cardioembolic strokes are common however atrial fibrillation, the most common cause, is often asymptomatic and difficult to detect. There is evidence that infarct topography and volume on magnetic resonance imaging may be associated with specific stroke etiologies.Aim: A systematic review and meta-analysis were undertaken to summarize the available evidence on the association between stroke etiology, infarct topography, and volume.Methods: A systematic review was conducted using Medline (OVID), Embase (OVID), and PubMed databases. Hand searches of the gray literature and of reference lists in relevant articles were also performed. A quality assessment was undertaken, based on the STROBE checklist. For each study, the number of patients with and without a CE source of stroke and infarct topography was collected and outcomes presented as odds ratios (OR) with 95% CI and p-values.Results: Four thousand eight hundred and seventy-three patients with ischemic stroke were included, of whom 1,559 were determined to have a CE source. Bilateral infarcts (OR 3.41; 95% CI 2.20–5.29; p < 0.0001) and multiple territory infarcts (OR 1.57; 95% CI 1.12–2.21; p = 0.009) were more common in patients with a CE source of stroke, than patients without a CE source. Lacunar infarcts (OR 0.49; 95% CI 0.31–0.80; p = 0.004) were more likely to occur in patients without a CE source. No significant difference between the frequency of multiple infarcts (OR 0.96; 95% CI 0.57–1.61; p = 0.87) anterior circulation (OR 1.45; 95% CI 0.83–2.53; p = 0.19) or posterior circulation infarcts (OR 1.06; 95% CI 0.72–1.57; p = 0.75), between the two groups were identified. Three out of four studies examining volume, found a significant association between increased infarct volume and CE source of stroke. A sensitivity analysis with cryptogenic and undetermined stroke sources assumed to be cardioembolic, did not alter the associations observed.Conclusion: The findings of this systematic review and meta-analysis are broadly consistent with previous literature and provide more robust evidence on the association between infarct topography, volume and stroke etiology. Our findings may assist with refining cardiac investigations for patients with cryptogenic stroke, based on infarct topography.

Background and purpose: Midline shift is a life-threatening complication of acute large artery occlusion (LAO). The value of superficial middle cerebral vein (SMCV) for predicting midline shift is currently unclear for patients with acute LAO.Methods: Consecutive acute LAO (middle cerebral artery M1 ± intracranial internal carotid artery) patients between March 2018 and May 2019 were included. Absent filling of ipsilateral cortical vein (marked as SMCV–) was defined as no contrast filling into the vein across the whole venous phase of four-dimensional computed tomography (CT) angiography derived from CT perfusion in the ischemic hemisphere.Results: In the total of 81 patients, 31 (38.4%) were identified as SMCV–. SMCV– independently predicted midline shift, with sensitivity of 87.5% and specificity of 82.5%. Receiver operating characteristic analysis showed that including SMCV– as a predictor in addition to baseline ischemic core volume significantly increased the area under the curve in predicting midline shift (SMCV– with baseline ischemic core volume vs. baseline ischemic core volume: AUC = 0.903 vs. 0.841, Z = 2.451, P = 0.014).Conclusion: In acute LAO patients, the presence of SMCV– was a sensitive and specific imaging marker for midline shift. SMCV– had supplementary value to baseline ischemic core volume in predicting midline shift.

Background: Admission outside normal business hours has been associated with prolonged door-to-treatment times and poorer patient outcomes, the so called “weekend effect. ” This is the first examination of the weekend effect in a telestroke service that uses multi-modal computed tomography.Aims: To examine differences in workflow and triage between in-hours and out-of-hours calls to a telestroke service.Methods: All patients assessed using the Northern New South Wales (N-NSW) telestroke service from April 2013 to January 2019 were eligible for inclusion (674 in total; 539 with complete data). The primary outcomes measured were differences between in-hours and out-of-hours in door-to-call-to-decision-to-needle times, differences in the proportion of patients confirmed to have strokes or of patients selected for reperfusion therapies or patients with a modified Rankin Score (mRS ≤ 2) at 90 days.Results: There were no significant differences between in-hours and out-of-hours in any of the measured times, nor in the proportions of patients confirmed to have strokes (67.6 and 69.6%, respectively, p = 0.93); selected for reperfusion therapies (22.7 and 22.6%, respectively, p = 0.56); or independent at 3 months (34.8 and 33.6%, respectively, p = 0.770). There were significant differences in times between individual hospitals, and patient presentation more than 4.5 h after symptom onset was associated with slower times (21 minute delay in door-to-call, p = 0.002 and 22 min delay in door-to-image, p = 0.001).Conclusions: The weekend effect is not evident in the Northern NSW telestroke network experience, though this study did identify some opportunities for improvement in the delivery of acute stroke therapies.

Background: Mobile stroke units (MSU) have been proposed to expedite delivery of recombinant tissue plasminogen activator (tPA) and expedite endovascular clot retrieval (ECR). Unexplored questions in the use of MSU include: maximal distance from base, time limit with regards to the use CT imaging, CT Angiography, CT Perfusion, and Telemedicine. We developed a computational model as an app (https://gntem3.shinyapps.io/ambmc/), taking into account traveling time to explore this issue. The aim of this study was to define the operating parameters for an MSU in a large metropolitan city, based on the geography of Melbourne.Methods: There are 2 hospitals (Royal Melbourne Hospital/RMH, Monash Medical Center/MMC) designated to provide state-wide ECR services. In these spatial simulations, the MSU is based at RMH and delivers tPA at the patient's pick-up address and then takes the patient to the nearest ECR center. We extracted the geocode of suburbs in Melbourne and travel time to each hospital using ggmap, an interface to Google Map API. The app contains widgets for varying the processing time at the patient location (default = 30 min), performing CT angiography (default = 10 min), performing telemedicine consultation (default = 15 min). The data were compared against those for usual ambulance metrics (default traveling time = 15 min, processing time at patient's location = 20 min, door to tPA = 60 min, door to groin = 90 min). Varying the widgets allow the viewer to explore the trade-off between the variable of interest and time to therapy at a suburb level.Results: The MSU was superior for delivering tPA to all Melbourne suburbs (up to 76 min from RMH). If the CTA times or processing time at location increased by 20 min then it was superior for providing ECR to only 74.9% of suburbs if the return base was RMH. Addition of CT Perfusion or telemedicine consultation affect the ability of a single hospital to provide ECR but not tPA if these additions can be limited to 20 min. Conclusion: The app can help to define how best to deploy the MSU across Melbourne. This app can be modified and used to optimize operating characteristics of MSU in other centers around the world.

Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke.Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset.Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7–16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges.Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.

Background and purpose Tenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore the efficacy and safety of TNK in Chinese patients who had an acute ischaemic stroke with large/medium vessel occlusion in an extended time window.Methods and design Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II) is a multicentre, prospective, block-randomised, open-label, blinded-endpoint, phase IIb study. Eligible patients are 1:1 randomised into two groups: 0.25 mg/kg TNK versus best medical management (excluding TNK). The safety and efficacy of 0.25 mg/kg TNK are assessed through reperfusion status and presence of symptomatic intracranial haemorrhage (sICH).Study outcomes The primary outcome is major reperfusion without sICH at 24–48 hours after randomisation. Major reperfusion is defined as restoration of blood flow to greater than 50% of the involved ischaemic territory assessed by catheter angiography or repeated perfusion imaging. Secondary outcomes include post-thrombolytic recanalisation, neurological improvements, change in the National Institutes of Health Stroke Scale score, haemorrhagic transformation at 24–48 hours, systematic bleeding at discharge, modified Rankin Scale (mRS) 0–1, mRS 0–2, mRS 5–6, mRS distribution and Barthel index at 90 days.Discussion CHABLIS-T II will provide important evidence of intravenous thrombolysis with TNK for patients who had an acute stroke in an extended time window.

Background The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window.Methods The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon’s two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5–24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5–10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24–48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis.Results A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon’s two-stage design.Discussion Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5–24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety.Trial registration number ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).

Background and purpose Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours.Methods and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5–24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume 6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.Discussion TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours.Trial registration number NCT05141305.

Background The optimal time to commence anticoagulation in patients with atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA) is unclear, with guidelines differing in recommendations. A limitation of previous studies is the focus on clinically overt stroke, rather than radiologically obvious diffusion-weighted imaging ischaemic lesions. We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1 month in patients commenced on early (5 mL, regardless of anticoagulation timing.Conclusion Commencing anticoagulation