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BackgroundThe Alteplase compared to Tenecteplase (AcT) randomized controlled trial (RCT) showed that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known, however the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase.MethodsPatients included were from AcT, a pragmatic, registry linked, phase 3 RCT comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4·5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin scale(mRS) 0-1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality rates. Mixed effects logistic regression was used to assess a)the association of stroke symptom onset to needle time (ONT), b)door (hospital arrival) to needle time(DNT) with outcomes and c)if these associations were modified by type of thrombolytic administered (tenecteplase vs. alteplase), after adjusting for age, sex, baseline stroke severity and site of intracranial occlusion.ResultsOf the 1538 patients included in this analysis, 1146(74.5%)[591: tenecteplase, 555 alteplase] presented within 3 hours vs. 392 (25.5%)[196: TNK, 196 alteplase] who presented within 3-4.5 hours of symptom onset. Baseline patient characteristics in the 0-3 hour versus 3-4.5-hour time window were similar, except patients in the 3-to-4.5-hour window had lower median baseline NIHSS (10 vs 7 respectively) and lower proportion of patients with large vessel occlusion on baseline CT Angiography (26.9% vs 18.7% respectively). Type of thrombolytic agent (tenecteplase vs. alteplase) did not modify the association between ONT(pinteraction= 0.161) or DNT(pinteraction= 0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-min reduction in ONT was associated with a 1.8% increase while every 10 min reduction in DNT was associated with a 0.2% increase in the probability of achieving 90-day mRS 0-1 respectively.ConclusionThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.Key points:QuestionIn patients with acute ischemic stroke, does the effect of time to thrombolysis on clinical outcomes differ with tenecteplase vs. alteplase administration?FindingsIn this analysis from the alteplase compared to tenecteplase (AcT) trial, a pragmatic, registry linked, phase 3 randomized controlled trial, each 30-min reduction in stroke onset to thrombolysis start time was associated with a 1.8% increase in the probability of achieving excellent functional outcome, which means that for every 30-minute reduction in onset to needle time two more of a 100 people achieved an excellent outcome. This effect was not modified by type of thrombolytic used (alteplase versus tenecteplase)MeaningThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.

Background:Cervico-cephalic arterial dissections (CeAD) are an important cause of stroke in young patients. This study aimed to determine the frequency and predictors of recanalization in spontaneous CeAD and to study the effect of recanalization on functional outcomes.Methods:We identified patients presenting with acute ischemic stroke secondary to CeAD from the CT angiography (CTA) database of the Calgary Stroke Program. Dissections were diagnosed based on standard clinical and imaging findings. At the discretion of treating stroke Neurologists, the patients were either treated with single antiplatelet or dual antiplatelet or triple therapy. Follow-up imaging with CTA, magnetic resonance imaging, and DSA was completed, and a Modified Rankin scale (mRS) was performed to determine the outcome.Results:Fifty-six patients with CeAdD were studied. Thirty-four patients (18 VAD; vertebral artery dissection and 16 CAD; carotid artery dissection) were followed up for recanalization. Complete recanalization was observed in 27 subjects; 13 patients with VAD recanalized in comparison to 14 with CAD (p = 0.40). All non-recanalized patients had hypertension. A good clinical outcome (mRS ≤ 2) was observed in 47 patients. Interestingly, the likelihood of a good neurological outcome was not influenced by recanalization status. There was no difference in clinical outcome for different sites in VAD, whereas patients with intracranial CAD had severe strokes (NIHSS > 21).Conclusions:CeAD has good recanalization rates and neurological outcomes, with recanalization seen even in vessels with initial complete occlusion. The presence of hypertension may influence recanalization. The efficacy of dual antiplatelets and heparin for early recanalization needs to be assessed in future clinical trials.

Background The relationship between duration of transient neurological events and presence of diffusion‐weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion‐weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal‐only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one‐third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.

Background: Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT. Methods: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes. Results: A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,17.2 [10.5-23]; IV-tPA use, 36%; Stent-Retrievers [SR], 27%; Contact Aspiration [CA], 27%; Combined SR + CA, 43%) were included. The median [IQR] number of passes was 1 [1-2]. FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for RBC-rich (P Conclusion: Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.

Background: Subgroup analyses are widely used to evaluate heterogeneity of treatment effects in randomized clinical trials. However, there is a limited investigation of the quality of prespecified and reported subgroup analyses in stroke trials. This study evaluated the credibility of subgroup analyses in stroke trials. Methods and Analysis: We searched Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception to March 24 th , 2021. Three reviewers screened, extracted, and analyzed the data from the publications. Primary publications of stroke trials that reported at least one subgroup effect and had published corresponding study protocols were included. The Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) was used to examine the quality of the subgroup effects reported. The risk of bias was assessed using the Cochrane Risk-of-Bias tool for randomized trials version 2. Results: Seventy-four articles met the inclusion criteria and altogether reported 647 subgroup effects. The median sample size was 1264 (interquartile range (IQR): 380 - 3876) while the median number of subgroups prespecified in the protocol was 6 (IQR:2 - 10), and 61 studies (82.4%) used the univariate test of interaction. One hundred and thirty-nine subgroup effects (43.6%) in acute stroke treatment and 131 subgroup effects (35.03%) in studies published in 2015 or later had moderate credibility. Overall, 458 subgroup effects (70.8%) had low credibility, while 189 subgroup effects (29.2%) had moderate credibility. Conclusion: Subgroup analysis reporting quality in stroke trials remains poor. Trialists and medical journal publishers must ensure that reporting guidelines, such as ICEMAN, are adopted to improve the credibility of reported subgroup analyses in stroke trials.

Introduction: Brain-selective hypothermia is a promising neuroprotectant in acute ischemic stroke. However, a non-invasive bedside method to monitor brain temperature during cooling is lacking. We tested the feasibility and accuracy of measuring brain temperature non-invasively using sensors designed to monitor core body temperature. Methods: In this prospective single-center study, 20 patients with large or medium vessel occlusion strokes were enrolled. Patients underwent a 3T MR spectroscopy imaging (MRSI, the reference standard) and zero heat flux (ZHF) core temperature sensor measurements (3M TM Bair Hugger TM ) within 12-72 hours from admission. Two ZHF sensors were placed on each side of the forehead on the side of stroke and contralateral side and the temperatures were checked before and after MRSI. A 2x2x2 cm voxel was centered on the infarct and matching contralateral location using diffusion weighted imaging. Brain temperature on MRSI was calculated using the relative chemical shifts of water and N-acetyl aspartate. Temperature measurements of the ZHF sensors were compared to MRSI measurements. Results: The brain temperature of stroke and contralateral sides were similar using MRSI or using ZHF sensors when each modality was compared to itself by hemisphere (all p>0.05). However, there was a significant difference for the ipsilateral side: median (SD) temperatures using MRSI was 36.0°C (1.8) vs 36.8°C (0.5) for sensor measurement. Bland-Altman plots showed that 95% of the observations fell within upper and lower limits of agreement of -2.1 to +3.7°C while 61% of observations fell within an agreement limit of +/- 1°C. There was an indication of an overall higher temperature measurements using the ZHF sensors compared to MRSI (Figure 1). Conclusions: More studies are needed to validate the use of ZHF thermometry in ischemic stroke including studies implementing hypothermia. Figure 1. Boxplot of stroke side MRSI compared to zero-heat-flux sensors.

The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions. Ultimately, the approach we outline here could become the foundation for a general justification for deferral of consent.

Background: 90-day home-time, the number of days a patient is back at their premorbid living situation without an increase in level of care in the first 90 days post stroke, is routinely collected in administrative data. We evaluated the prediction of 90-day home-time using machine learning modelling in patients undergoing endovascular treatment (EVT). Methods: We used the QuICR provincial stroke registry and administrative data from Southern Alberta from Jan 2015-Dec 2019 to identify patients who underwent EVT. Imaging data were scored by 2-physician consensus. The primary outcome was 90 day home-time, which has a highly non-normal distribution with excess zero’s. We modelled using generalized boosting machine model with Gaussian distribution. Contribution of different covariates to hometime was determined using partial dependence plots. Results: We identified 659 EVT patients from Jan 2015 to Dec 2019 treated in Calgary, Alberta. Overall,median predicted 90d home-time was 41days (IQR 5.5 to 77.8) with good model accuracy (Root mean square error 6.96). Holding other covariates constant, factors predicting lower 90d-hometime were diabetes mellitus(-14.1d), hypertension (-7d), low baseline ASPECTS (≤5) (-5.6d) and symptomatic intracerebral hemorrhage (sICH) on follow up scan (-13.8d). There was a consistent improvement in the predicted home-time over the last 5 years. There was no meaningful difference in predicted 90d-home-time by age, baseline NIHSS, sex, atrial fibrillation, occlusion site, tandem occlusion, thrombolysis, or successful reperfusion (Figure 1) Conclusions: Predicting 90-d hometime using boosting machine learning modelling is useful to assess complex relationships between predictors and home-time. Hypertension, diabetes, low ASPECTS and sICH were predictors of lower 90-d home-time in this registry.

Background: Trials’ data are increasingly re-analyzed to identify treatment effect heterogeneity: that is, subgroups of patients who have either enhanced or adverse effects in a trial. This study investigates the robustness of subgroup identification methods in an acute stroke trial. Methods and Analysis: The Model-based recursive partitioning (MOB), Stochastic Subgroup Identification based on Differential Effects Search (Stochastic SIDEScreen), and Virtual Twin (VT) methods would be used to detect heterogeneity in Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Results: In the ESCAPE trial, patients in the intervention group had a higher rate of functional independence (90-day mRS 0-2) than those in the control group (OR=2.6; p 11 group showing a significant treatment effect (OR=3.67; p 11 had significant treat effect (OR=5.11; p Conclusion: Data-driven subgroup identification methods provide insight into the heterogeneity of treatment effects in acute stroke trials. Information about the identified subgroups might inform the development of clinical practice guidelines for acute stroke management.

Introduction: First-pass effect (FPE), i.e., achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly being used as a marker of device and procedural efficacy. We evaluated the ability of thrombus-based radiomics models to predict FPE in patients undergoing endovascular thrombectomy (EVT) and compare performance to experts and non-radiomics thrombus characteristics. Methods: Patients with thin-slice non-contrast CT and CT angiography from The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial were included. Thrombi were manually segmented on all images. Data was randomly split into a derivation set that included a training and a validation subset and an independent test set. Radiomics features were extracted from the derivation data set. Three expert stroke physicians reviewed baseline imaging and clinical data for the test set. The machine learning (ML) models were compared to the three experts in predicting the primary outcome (FPE) in the test set using area under the receiver operating characteristic curves (AUC-ROC). Results: A total of 554 patients with available thin-slice images comprised of a derivation set (training subset [n=388, 70%]), validation subset [n=55, 10%]), and a test set (n=111, 20%). FPE was seen in 31.8% in the derivation set and 31.5 % in the test set. AUC of the best radiomics model was 0.74 (95% CI: 0.64, 0.84), which was higher than the mean AUC of the three experts 0.60 (95% CI: 0.50, 0.71) ( P =0.009). Specificity of radiomics was better than the mean specificity of the three experts, 46 of 76 (60%) vs. 35 of 76 (46.4%), P =0.004, whereas sensitivity was not significantly different between radiomics (28 of 35 [79%]) and experts (27 of 35 [77%]). Moreover, radiomics features performed better than non-radiomics features such as thrombus volume and permeability measurements in predicting FPE ( P Conclusion: A radiomics-based ML model of thrombus characteristics on non-contrast CT and CT angiography performs better than experts and non-radiomics image characteristics in predicting FPE in patients with acute stroke treated with EVT.

Background: The outcome in stroke patients with ASPECTS of ≤5 who undergo Endovascular Thrombectomy(EVT) in Large Vessel Occlusion (LVO) is uncertain. We used machine learning models to predict 90-day home-time in these patients. Methods: We used the QuICR provincial stroke registry and administrative data from Southern Alberta to identify patients who underwent EVT from Jan 2015-Dec 2019. Imaging data were scored by 2-physician consensus. The primary outcome was the predicted 90-day home-time(number of days a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using generalized boosting machine model with Gaussian distribution. Covariate contribution to hometime was determined using partial dependence plots. Results: Of 659 EVT patients, 82(12%) had baseline ASPECTS ≤5(mean age 69.8y, 44.6% females, 93% good-moderate collaterals, M1 occlusion(64.1%). Overall, patients with low ASPECTS had lower median predicted home-time by 2.8d. Holding other covariates constant, factors predicting lower 90d-home-time were diabetes mellitus(-14d), hypertension(-7d), and symptomatic intracerebral hemorrhage (sICH) on follow up scan(-14d). Home-time decreased with increasing age in both low and non-low ASPECTS groups, but the difference was larger in older age groups (Figure). There was no meaningful difference in predicted 90d-home-time by sex, atrial fibrillation, baseline NIHSS, occlusion site, tandem lesion, thrombolysis, or successful reperfusion. Conclusions: Among patients with low ASPECTS who underwent EVT, hypertension, diabetes and sICH predicted lower 90-d home-time. .

Introduction: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) in ESUS patients on CT angiography (CTA) to characterize high-risk plaque features. Methods: All patients from two prospective multicenter studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the etiology was recorded. Three independent readers analyzed the following AAA plaque features on CTA at the time of acute ischemic stroke: 1) thickness in mm (radial measurement at thickest point); 2) morphology (Figure a-c): none, smooth, ulcerated, or protruding; 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (Figure a, d-f): none, single small, multiple small, single large, or diffuse extensive. Reader disagreement was resolved by consensus. Results: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men). The mean AAA thickness was significantly larger in ESUS versus non-ESUS patients (3.8 vs 3.0 mm, p95 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). Conclusions: ESUS patients had thicker AAA plaques and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features could be a potential cause of acute ischemic stroke in the ESUS population.

Background and Purpose: Sex-related differences exist in many aspects of stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment (EVT) in the late time window. Methods: Analyses were based on the Selection Of Late-window Stroke for Thrombectomy by Imaging Collateral Extent Consortium, which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, functional independence (modified Rankin Scale ≤ 2), mortality, and symptomatic intracranial hemorrhage (sICH) were compared between women and men. Effect of sex on the association between age, successful reperfusion (Thrombolysis in cerebral infarction 2b-3) and outcomes was assessed using multivariable logistic regression with interaction terms. Results: Among 608 patients treated with EVT, 50.5% were women. Women were older than men by median 4 years and had a lower prevalence of tandem occlusions (14.0% vs. 22.9%). In the subset of patients with available perfusion volumes (n= 195), women had smaller penumbra (median IQR:97 mL [60- 130] vs. 109 mL [73-189]; p= 0.008), and mismatch volumes, (79 mL [49-101] vs. 91 mL [57-158] ; p= 0.02). Pre and intrahospital times were similar between sexes. Outcomes did not differ between women and men, and there was no sex-by-age interaction on functional independence. However, men had higher likelihood of mortality (p interaction = 0.004) and sICH (p interaction = 0.016) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late presenters treated with EVT, sex was not associated with clinical outcomes. However, sex influenced the association between age and safety outcomes with men experiencing worse outcomes with advancing age.

Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared using the area under the receiver operating characteristic curve (AUC). Shapley values were used to determine marginal contributions of variables to outcome variance in the regression models. Results Among 1105 patients, functional independence was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95% CI, 0.71–0.77); this iteratively improved when treatment and posttreatment variables were added to the models (model 2: AUC, 0.77; 95% CI, 0.74–0.80; model 3: AUC, 0.80; 95% CI, 0.77–0.83; model 4: AUC, 0.82; 95% CI, 0.79–0.85). With baseline variables alone, 26% of patients who achieved functional independence were erroneously classified as not achieving functional independence. Even with the most comprehensive model, 19.8% of patients were misclassified as such. Patient age contributed most to outcome variance (Shapley value, 0.28), followed by severe adverse events including pneumonia (0.16) and intracranial hemorrhage at 24‐hours imaging (0.13). Conclusions A substantial contribution to outcomes after endovascular therapy comes from factors unrelated to currently collected baseline patient variables. One‐fifth of patients achieving functional independence were misclassified as not achieving independence, even with the most comprehensive model. Our findings suggest that the achievable accuracy of current outcome prediction models is limited, and caution should be used when applying them in clinical practice.

Ultra-Reliable and Low Latency Communications (URLLC) is one of the essential services in 5G networks and beyond. The coexistence of URLLC alongside other service classes, namely, enhanced Mobile BroadBand (eMBB) and massive Machine-Type Communications (mMTC), calls for developing spectrally efficient multiplexing techniques. In this work, we study the problem of scheduling URLLC traffic in a downlink system with the presence of eMBB traffic class. Based on the superposition/puncturing scheme, a resource allocation problem is formulated with the objective to minimize the eMBB data rate loss while satisfying eMBB and URLLC quality of service (QoS) constraints. The resulting problem is formulated as a mixed integer non-linear programming (MINLP) which is generally NP hard and hence complex to solve. Hence, we derive its feasibility region as well as the optimal solutions for the power and spectral resource allocation. Subsequently, we propose a low complexity algorithm to serve URLLC traffic. Simulation results show that the proposed algorithm achieves higher reliability for URLLC and higher eMBB data rate compared to the puncturing schemes. The results also show that the eMBB QoS requirements, which are represented by the eMBB rate loss threshold, has a negative effect on the URLLC reliability for high URLLC load. Therefore, the eMBB rate and the eMBB loss threshold should be jointly optimized considering QoS of both eMBB and URLLC. Index Terms—eMBB, multiplexing, puncturing, superposition, URLLC, 6G.

This paper studies the coexistence of enhanced mobile broadband (eMBB) and ultra-reliable and low-latency communication (URLLC) services in a cellular network that is assisted by a reconfigurable intelligent surface (RIS). The system model consists of one base station (BS) and one RIS that is deployed to enhance the performance of both eMBB and URLLC in terms of the achievable data rate and reliability, respectively. We formulate two optimization problems, a time slot basis eMBB allocation problem and a mini-time slot basis URLLC allocation problem. The eMBB allocation problem aims at maximizing the eMBB sum rate by jointly optimizing the power allocation at the BS and the RIS phase-shift matrix while satisfying the eMBB rate constraint. On the other hand, the URLLC allocation problem is formulated as a multi-objective problem with the goal of maximizing the URLLC admitted packets and minimizing the eMBB rate loss. This is achieved by jointly optimizing the power and frequency allocations along with the RIS phase-shift matrix. In order to avoid the violation in the URLLC latency requirements, we propose a novel framework in which the RIS phase-shift matrix that enhances the URLLC reliability is proactively designed at the beginning of the time slot. For the sake of solving the URLLC allocation problem, two algorithms are proposed, namely, an optimization-based URLLC allocation algorithm and a heuristic algorithm. The simulation results show that the heuristic algorithm has a low time complexity, which makes it practical for real-time and efficient multiplexing between eMBB and URLLC traffic. In addition, using only 60 RIS elements, we observe that the proposed scheme achieves around 99.99\% URLLC packets admission rate compared to 95.6\% when there is no RIS, while also achieving up to 70\% enhancement on the eMBB sum rate.

There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome.Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories ("other infarcts"). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0-2 at 90 days), excellent outcome (mRS 0-1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome.Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (

Deciding about whether an unruptured intracranial aneurysm (UIA) should be treated or not is challenging because robust data on rupture risks, endovascular treatment complication rates, and treatment success rates are limited. We aimed to investigate how neurointerventionalists conceptually approach endovascular treatment decision-making in UIAs.In a web-based international multidisciplinary case-based survey among neurointerventionalists, participants provided their demographics and UIA treatment-volumes, estimated 5-year rupture rates, endovascular treatment complication and success rates and gave their endovascular treatment decision for 15 pre-specified UIA case-scenarios. Differences in estimated 5-year rupture rates, endovascular treatment complication and success rates based on physician and hospital characteristics were evaluated with the Kruskal-Wallis test. Multivariable logistic regression analysis was used to derive adjusted effect size estimates for predictors of endovascular treatment decision.Two hundred-thirty-three neurointerventionalists from 38 countries participated in the survey (median age 47 years [IQR: 41-55], 25/233 [10.7%] females). The ranges of estimates for 5-year rupture risks, endovascular treatment complication rates, and particularly endovascular treatment success rates were wide, especially for UIAs in the posterior circulation. Estimated 5-year rupture risks, endovascular treatment complication and success rates differed significantly based on personal and institutional endovascular UIA treatment volume, and all three estimates were significantly associated with physicians' endovascular treatment decision.Although several predictors of endovascular treatment decision were identified, there seems to be a high degree of uncertainty when estimating rupture risks, treatment complications, and treatment success for endovascular UIA treatment. More data on the clinical course of UIAs with and without endovascular treatment is needed.

Evidence for efficacy and safety in stroke patients ≥80 years is limited, since they were underrepresented in randomized thrombectomy trials. This study sought to explore how physicians approach endovascular therapy (EVT) decision making in octogenarians and nonagenarians under their current local resources under assumed ideal conditions, i.e. without external (monetary or infrastructural) limitations.In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 out of a pool of 22 case scenarios with different evidence levels for EVT, 4 of which involved octogenarians and 2 nonagenarians, and asked how they would treat the patient in the given scenario A) under their current local resources and B) under assumed ideal conditions, i.e. with no external restraints. Decision rates were calculated and clustered multivariable regression analysis performed to determine adjusted measures of effect size for patient age.In octogenarians, physicians decided in favor of EVT in 76.7% (all of which were level 2B evidence scenarios) under current local resources and in 80.2% under assumed ideal conditions. In nonagenarians, 74.0% decided in favor of EVT under current local resources (level 1A scenarios: 87.7%, level 2B scenarios: 60.3%) and 79.2% would offer EVT under assumed ideal conditions (level 1A scenarios: 91.3%, level 2B scenarios: 67.2%). Age was not a significant predictor for treatment decision under current local resources (adjusted odds ratio, OR: 0.99, confidence interval, CI: 0.96-1.02 per decile increase) and under assumed ideal conditions (adjusted OR: 1.00, CI 0.97-1.03 per decile increase).The vast majority of physicians participating in this survey would offer EVT to acute ischemic stroke patients above 80 years.

Background and Purpose- We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods- Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital. The primary outcome was disability defined on the modified Rankin Scale at 3 months. Results- Among 601 patients, mean age was 66.0 years (SD, 13.9), 50% were women, and median National Institutes of Health Stroke Scale score was 17. Onset-to-treatment time was median 125 minutes (interquartile range, 90-170). Door-to-treatment time was median 38 minutes (interquartile range, 26-55). Each 60-minute onset-to-treatment time delay was associated with greater disability at 90 days; the odds of functional independence (modified Rankin Scale, 0-2) at 90 days was 0.82 (95% CI, 0.66-1.03). With each 60-minute delay in door-to-needle time; the odds of functional independence was 0.55 (95% CI, 0.37-0.81) at 90 days. The absolute decline in the rate of excellent outcome (modified Rankin Scale, 0-1 at 90 days) was 20.3 per 1000 patients treated per 15-minute delay in door-to-needle time. The adjusted absolute risk difference for a door-to-needle time30 minutes versus 30 to 60 minutes was 19.3% for independent outcome (number-needed-to-treat ≈5 to gain 1 additional good outcome). Symptomatic intracranial hemorrhage occurred in 3.4% of patients, without a significant time dependency: odds ratio, 0.74 (95% CI, 0.43-1.28). Conclusions- Faster intravenous thrombolysis delivery is associated with less disability at 3 months among patients with large vessel occlusion.

Background and Purpose- Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods- Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0-6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results- Median (interquartile range) serum glucose on admission was 120 (104-140) mg/dL (6.6 mmol/L [5.7-7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69-2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucoseor90 mg/dL (5.0 mmol/L; P=0.019 for interaction; acOR, 3.81; 95% CI, 1.73-8.41 for patients90 mg/dL versus 1.83; 95% CI, 1.53-2.19 for patients90 mg/dL), and glucoseor100 mg/dL (5.5 mmol/L; P=0.004 for interaction; acOR, 3.17; 95% CI, 2.04-4.93 versus acOR, 1.72; 95% CI, 1.42-2.08) but not between subgroups above these levels of glucose. Conclusions- EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0-5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.

Background: In the setting of acute ischemic stroke, CT Perfusion (CTP) may change thrombolytic/endovascular treatment decisions when compared to NCCT/CTA alone. Two distinct thresholds may be useful in this regard: separation of 1) non-salvageable tissue (infarct core) from salvageable electrically silent tissue (penumbra), and 2) penumbra from benign oligemia (hypoperfused, but will survive if clot persists). Methods: CTP (120s,8cm) was performed on 180 patients within 12hrs of ischemic stroke. Two patient cohorts were analyzed: (1) recanalization (TICI 2b,3) 6s. For group (2) CBF, CBV, and Tmax values were obtained from within the final infarct region, and total ipsilateral hemisphere, excluding infarction. CBF, CBV and Tmax were used in univariate regression models. Results: For group (1)[n=11], mean time from CTP to recanalization was 60±19min. CBF parameter (thresholds for gray and white matter 7.2 and 5.2 ml•min-1•(100g)-1) had the highest sensitivity (90.9%) and specificity (81.8%) for infarction. For group (2)[n=15], the Tmax parameter (thresholds for gray and white matter 11.3s and 11.8s) had the highest sensitivity (86.6%) and specificity (80.0%) for penumbra. Conclusion: CTP thresholds derived from ultra-early reperfusers could potentially best define what is clinically dead in patients with acute ischemic stroke