Extended Time Window Research Articles

Endovascular treatment in patients with acute ischemic stroke presenting beyond 6 h after symptom onset: An international multicenter cohort study of the EVA-TRISP collaboration.

After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results. Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows. We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3. According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

In the RESCUE BT (endovascular treatment with versus without tirofiban for stroke patients with large vessel occlusion) trial, enrollment in extended time window was based on noncontrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6h window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48h and 90-day mortality. A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median interquartile ranges (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% CI: 0.83-1.42). The incidence of sICH [10.1% versus 6.3%; adjusted OR 1.70; (95% CI: 0.95-3.04)] was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level [adjusted common OR, 1.74 (95% CI: 1.14-2.65); P =0.01] in patients with large artery atherosclerosis. There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. The authors observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

Treatment outcome of bridge mechanical thrombectomy with different IV-tPA dosages in the standard and extended time window in real-world practice.

Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows. Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9mg/kg) or reduced (<0.9mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6h of acute ischemic stroke onset, while those beyond 6h as the extended window (EW) cohort. 90days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199). In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.

IV Thrombolysis for Acute Ischemic Stroke with Unknown Onset in Patients on Oral Anticoagulation

Introduction: IV thrombolysis (IVT) is established in the unknown or extended time window based on multimodal imaging. Further, increasing evidence exists regarding IVT in patients on oral anticoagulation including direct oral anticoagulants (DOACs). However, data on IVT in ischemic stroke patients on oral anticoagulation with unknown time of stroke onset are sparse. Methods: This study bases on the longitudinal cohort study Stroke Research Consortium in Northern Bavaria (STAMINA; ClinicalTrials.gov Identifier: NCT04357899). Acute ischemic stroke patients treated with IVT in the unknown or extended time window from January 2015 to December 2019 were included. Patient selection was based on multimodal CT or MRI. Patients on oral anticoagulation (vitamin-K antagonist [VKA] or DOAC within 48 h) were eligible for IVT based on INR measurement (VKA) or plasma levels (DOAC) according to an institutional protocol. Primary outcomes were the incidence of any and symptomatic intracranial hemorrhage. Results: Of 170 ischemic stroke patients treated with IVT in the unknown or extended time window, 151 had no oral anticoagulation at stroke onset and 19 were on oral anticoagulation (6 on VKA and 13 on DOAC). The risk of symptomatic ICH according to ECASS II criteria was similar between the patients with and without oral anticoagulation (1 [5.3%] vs. 4 [2.7%], p = 0.453). After adjustment for confounding factors, pre-medication with oral anticoagulation was not associated with symptomatic ICH (aOR 1.02 [0.09–11.02], p = 0.988). Conclusion: IVT for ischemic stroke with unknown onset appeared safe in selected patients on oral anticoagulation with both DOAC and VKA.

Effectiveness of computed tomography perfusion imaging in stroke management.

Current guidelines do not support the use of computed tomography perfusion (CTP) in stroke, except when identifying the penumbra during an extended treatment window. Therefore, this study aimed to define the yield of CTP in diagnosing a stroke diagnosis beyond the imaging of the penumbra in the hyperacute phase (0-6 h) and an extended time window (6-24 h). All consecutive patients with acute onset of symptoms within a 24-h window underwent CTP imaging. The diagnostic value of CTP was calculated against the clinical and radiological diagnoses of stroke. A positive CTP result was determined by the presence of either a core or penumbra on the RAPID summary. Clinical diagnoses corresponded to discharge diagnoses of stroke. A radiological diagnosis was established if early ischemic changes [Alberta Stroke Program Early CT Score (ASPECTS) <10] were observed on the baseline CT scan, acute infarction was confirmed on follow-up imaging, or symptomatic occlusion was evident on baseline CTA. Between November 2018 and November 2019, 585 consecutive patients with an acute neurological deficit underwent multimodal CT imaging. A total of 500 patients (85%) were included, where 274 (55%) were within the hyperacute phase, 153 (31%) had a radiological diagnosis of stroke, and 122 (24%) had a clinical diagnosis of stroke. CTP yielded positive results only in patients with a confirmed stroke (positive predictive value and specificity of 100%). When CTP results were negative, 43% of the cases turned out to stroke mimics. Patients with stroke mimics were younger (66 ± 17 vs. 73 ± 13) and had lower scores on the National Institutes of Health Stroke Scale [median 0; interquartile range (IQR) 0-2 vs. median 4; IQR 2-6] compared to patients with CTP-negative strokes. In our study, CTP consistently indicated brain ischemia; therefore, in stroke management, CTP is most beneficial when it yields a positive result. A positive CTP result should prompt adequate stroke management actions without any delay. Conversely, a negative CTP result necessitates the consideration of both stroke and non-stroke diagnoses.

Impact of stroke imaging selection modality on endovascular thrombectomy outcomes in the early and extended time windows: A meta-analysis.

The effect of imaging selection modality on endovascular thrombectomy (EVT) clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) remains unclear. This study aims to compare post-EVT outcomes in patients with AIS-LVO who underwent basic imaging (computed tomography with or without computed tomography angiography) and advanced imaging (computed tomography perfusion or magnetic resonance imaging) in early and late time windows. A systematic literature search was conducted on PubMed, Cochrane Library, and Embase databases from inception until June 10, 2023. Studies investigating the relationship between the imaging selection modality and post-EVT outcomes in patients with AIS-LVO were retrieved. A random-effects model was used to pool the effect estimates of successful reperfusion, symptomatic intracranial hemorrhage (sICH), functional independence, and mortality. The meta-analysis was performed using Review Manager software v.4.3, and the outcomes were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). A total of 13 non-randomized observational studies, comprising 19,694 patients, were included in this meta-analysis. In the early time windows, AIS-LVO patients receiving advanced imaging demonstrated a higher likelihood of functional independence (OR, 1.25, 95% CI, 1.08-1.46) and a lower risk of mortality (OR,.73 95% CI,.61-.86) compared to those receiving basic imaging. In the extended time windows, AIS-LVO patients undergoing advanced imaging had a lower mortality rate (OR,.79, 95% CI,.68-.92). Regardless of the time of onset, there were no significant differences between the two groups in terms of sICH or successful reperfusion. Advanced imaging combined with EVT may achieve better clinical outcomes in patients with AIS-LVO. Further high-quality studies are needed to validate these findings.

Exploring temporal sensitivity in the brain using multi-timescale language models: an EEG decoding study

Abstract The brain’s ability to perform complex computations at varying timescales is crucial, ranging from understanding single words to grasping the overarching narrative of a story. Recently, multi-timescale long short-term memory (MT-LSTM) models (Mahto et al. 2020; Jain et al. 2020) have been introduced, which use temporally-tuned parameters to induce sensitivity to different timescales of language processing (i.e. related to near/distant words). However, there has not been an exploration of the relation between such temporally-tuned information processing in MT-LSTMs and the brain’s language processing using high temporal resolution recording modalities, such as electroencephalography (EEG). To bridge this gap, we used an EEG dataset recorded while participants listened to Chapter 1 of “Alice in Wonderland” and trained ridge regression models to predict the temporally-tuned MT-LSTM embeddings from EEG responses. Our analysis reveals that EEG signals can be used to predict MT-LSTM embeddings across various timescales. For longer timescales, our models produced accurate predictions within an extended time window of ±2 s around word onset, while for shorter timescales, significant predictions are confined to a narrow window ranging from −180 ms to 790 ms. Intriguingly, we observed that short timescale information is not only processed in the vicinity of word onset but also at distant time points. These observations underscore the parallels and discrepancies between computational models and the neural mechanisms of the brain. As word embeddings are used more as in silico models of semantic representation in the brain, a more explicit consideration of timescale-dependent processing enables more targeted explorations of language processing in humans and machines.

Cytoprotective agents in stroke: Still uncertainty in the next frontier

IntroductionDespite substantial improvement of acute ischemic stroke (AIS) care with the advent of extended time windows for intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), a substantial portion of patients still suffer poor outcomes. Additional adjuvant therapies are needed but pharmacologic interactions among therapies may dictate how they could be used. We conducted a survey to determine physician decision-making regarding the use of cytoprotective agents in patients presenting with AIS. MethodsThe survey was structured, web-based, anonymous, and invite-only among physicians across the world treating patients presenting with AIS. Respondents were asked about the use of a hypothetical cytoprotective agent (that provided an added 10% benefit) in the context of a treatment interaction with IVT or its timing in relation to IVT. ResultsA total of 282 stroke physicians (74.9% males, mean age 46 years) participated in the survey. When the respondent could give both the cytoprotective agent and IVT with no treatment interaction, 177 (78.0%) chose to administer both. In the presence of treatment interaction, 88 (38.3%) would withhold IVT, 83 (36.1%) would withhold the cytoprotective agent and 56 (24.4%) were uncertain. Lastly, 111 (48.9%) were willing to administer the cytoprotective agent if it meant a necessary 10-minute delay in IVT administration. ConclusionsPharmacologic interactions result in major uncertainty about cytoprotective treatment choices.

Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy

IntroductionBased on recent trials regarding the early time window, omitting intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in eligible patients seems unjustified. Whether this also concerns the extended time window, 4.5 to 9 h from last seen well, is yet unclear. Patients and methodsAll consecutive patients treated with IVT, EVT, or IVT plus EVT in the extended time window at Helsinki University Hospital (HUS) between 1/2021 and 12/2022 were compared with matched controls treated in the early time window between 1/2016 and 12/2020. Regression analysis was applied on functional outcome at 90 days, evaluated on modified Rankin Scale (mRS), and on the occurrence of symptomatic intracerebral hemorrhage (sICH), adjusted for potential confounders. ResultsAltogether 134 patients and 134 matching controls were included. Functional outcomes did not significantly differ between the extended versus early time window. Among patients with IVT plus EVT, the adjusted odds ratio (aOR) for a favorable outcome shift on mRS was 1.15, 95% confidence interval (CI) 0.54–2.43. Although sICH occurred more frequently (2.2% versus 3.0%) in the extended time window, regression analysis did not show a significant difference, aOR 0.96, 95% CI 0.14–6.87. Discussion and conclusionWe found no significant differences in the functional or safety outcomes between the extended versus early time window among patients with either IVT, EVT, or IVT plus EVT. There were no signals indicating, that IVT or EVT should be avoided in eligible patients in the extended time window which aligns with the current clinical treatment guidelines of HUS.

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. This study was registered at ClinicalTrials.gov under NCT04096248. This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. clinicaltrials.gov; Unique identifier: NCT04096248.

Controlled In Situ Self-Assembly of Biotinylated Trans-Cyclooctene Nanoparticles for Orthogonal Dual-Pretargeted Near-Infrared Fluorescence and Magnetic Resonance Imaging.

A pretargeted strategy that decouples targeting vectors from radionuclides has shown promise for nuclear imaging and/or therapy in vivo. However, the current pretargeted approach relies on the use of antibodies or nanoparticles as the targeting vectors, which may be compromised by poor tissue penetration and limited accumulation of targeting vectors in the tumor tissues. Herein, we present an orthogonal dual-pretargeted approach by combining stimuli-triggered in situ self-assembly strategy with fast inverse electron demand Diels-Alder (IEDDA) reaction and strong biotin-streptavidin (SA) interaction for near-infrared fluorescence (NIR FL) and magnetic resonance (MR) imaging of tumors. This approach uses a small-molecule probe (P-Cy-TCO&Bio) containing both biotin and trans-cyclooctene (TCO) as a tumor-targeting vector. P-Cy-TCO&Bio can efficiently penetrate subcutaneous HeLa tumors through biotin-assisted targeted delivery and undergo in situ self-assembly to form biotinylated TCO-bearing nanoparticles (Cy-TCO&Bio NPs) on tumor cell membranes. Cy-TCO&Bio NPs exhibited an "off-on" NIR FL and retained in the tumors, offering a high density of TCO and biotin groups for the concurrent capture of Gd-chelate-labeled tetrazine (Tz-Gd) and IR780-labeled SA (SA-780) via the orthogonal IEDDA reaction and SA-biotin interaction. Moreover, Cy-TCO&Bio NPs offered multiple-valent binding modes toward SA, which additionally regulated the cross-linking of Cy-Gd&Bio NPs into microparticles (Cy-Gd&Bio/SA MPs). This process could significantly (1) increase r1 relaxivity and (2) enhance the accumulation of Tz-Gd and SA-780 in the tumors, resulting in strong NIR FL, bright MR contrast, and an extended time window for the clear and precise imaging of HeLa tumors.

52Mn]Mn-BPPA-Trastuzumab: A Promising HER2-Specific PET Radiotracer.

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [52Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [52Mn]Mn isotope. In comparison to DOTA-GA-trastuzumab, the BPPA-trastuzumab conjugate exhibits a labeling efficiency with [52Mn]Mn approximately 2 orders of magnitude higher. In female CB17 SCID mice bearing 4T1 (HER2-) and MDA-MB-HER2+ (HER2+) xenografts, [52Mn]Mn-BPPA-trastuzumab demonstrated superior uptake in HER2+ cells on day 3, with a 3-4 fold difference observed on day 7. Overall, the hexadentate BPPA chelator proves to be exceptional in binding Mn(II). Upon coupling with trastuzumab as a BFC ligand, it becomes an excellent imaging probe for HER2-positive tumors. [52Mn]Mn-BPPA-trastuzumab enables an extended imaging time window and earlier detection of HER2-positive tumors with superior tumor-to-background contrast.

Is time really brain in stroke therapy?: A meta-analysis of mechanical thrombectomy up to 155h post ictus.

Mechanicalthrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24h). PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

Does the Ischemic Core Really Matter? An Updated Systematic Review and Meta‐Analysis of Large Core Trials After TESLA, TENSION, and LASTE

Background The available evidence supporting the use of endovascular thrombectomy (EVT) in acute ischemic stroke patients with large core has increased with the recent release of the Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke (TESLA), Efficacy and Safety of Thrombectomy In Stroke with Extended Lesion and Extended Time Window (TENSION), and Large Stroke Therapy Evaluation (LASTE) trials, providing critical information on additional subgroups not included in initial trials. We aimed to study the efficacy and safety of EVT in patients with acute ischemic stroke with large core and stratify by several subgroups including core infarct at presentation, using a comprehensive meta‐analysis of aggregate data. Methods We executed a systematic search to identify randomized controlled trials that compared EVT to medical management (MM) for the treatment of patients with acute ischemic stroke with large core, defined as Alberta Stroke Program Early CT [Computed Tomography] Score ≤5 on noncontrast CT and/or estimated ischemic core ≥50 mL on CT‐perfusion/MR diffusion. The primary outcome was the shift analysis in the 90‐day modified Rankin scale (mRS) score. Secondary outcomes included functional independence (mRS score 0–2), independent ambulation (mRS score 0–3), 90‐day mortality, and symptomatic intracranial hemorrhage. Pooled odds ratios were calculated for shift mRS score through the random‐effects meta‐analyses, and risk ratios (RRs) were used for the other outcomes, comparing EVT with MM alone. Results Out of 3402 titles and abstracts screened, 6 randomized controlled trials with 1886 patients were included. The EVT group had a higher shift toward a lower mRS than MM alone (odds ratio [OR], 1.49 [95% CI, 1.24–1.79]). Furthermore, the use of EVT was associated with higher rates of functional independence (19.5% versus 7.5%, RR, 2.49 [95% CI, 1.92–3.24]), independent ambulation (36.5% versus 19.9%, RR, 1.91 [95% CI, 1.51–2.43]), and symptomatic intracranial hemorrhage (5.5% versus 3.2%, RR, 1.73 [95% CI, 1.01–2.95]) compared with MM. There was no difference between the 2 groups regarding mortality (31.5% versus 36.8%, RR, 0.86 [95% CI, 0.72–1.02]). Importantly, EVT was consistently associated with a shift toward a lower mRS score in both Alberta Stroke Program Early CT Score 3–5 (OR, 1.60 [95% CI, 1.10–2.32]) and Alberta Stroke Program Early CT Score 0–2 (OR, 1.45 [95% CI, 1.17–1.80]) when compared with MM alone. Conclusion Our results confirm the efficacy of EVT for acute ischemic stroke with large core and suggest a consistent benefit across all Alberta Stroke Program Early CT Score categories. These results represent an important shift in the current large vessel occlusion selection paradigm that currently considers core as an effect modifier for EVT selection.

Anesthesia on Clinical Outcomes in an Extended Time Window During Endovascular Stroke Therapy: Exploratory Analysis of the ANGEL-ACT Registry.

Data on the impact of different anesthesia methods on clinical outcomes in patients with acute ischemic stroke undergoing endovascular therapy (EVT) in extended windows are limited. This study compared clinical outcomes in patients with stroke having general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA) during EVT in extended (>6 h) time windows. We conducted an exploratory analysis of data from the ANGEL-ACT registry. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included the proportions of patients with mRS scores of 0 to 1, 0 to 2, and 0 to 3, and safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, or mortality within 90 days. Multivariate analyses, inverse probability of treatment weighting, and coarsened exact matching were used to adjust for indication bias. A total of 646 patients were included in the analysis (GA,280; CS, 103; LA, 263). Patients having LA during EVT were more likely to have a favorable mRS score (adjusted odds ratio [aOR]: 1.75; 95% CI: 1.28 to 2.40) and a lower incidence of symptomatic ICH (aOR: 0.33; 95% CI: 0.14 to 0.76) than those having GA group. Similarly, CS was associated with greater odds of favorable 90-day mRS scores compared with GA (aOR: 1.69; 95% CI: 1.11 to 2.56). Posterior circulation stroke was overrepresented in the GA group (29.6%) and may be a reason for the worse outcomes in the GA group. Patients who received LA or CS had better neurological outcomes than those who received GA within extended time windows in a real-world setting.

Assessment of Perfusion Volumes by a New Automated Software for Computed Tomography Perfusion

IntroductionTo compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional...

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

Intravenous thrombolysis for ischemic stroke in the posterior circulation: A systematic review and meta-analysis.

ObjectivesIntravenous thrombolysis (IVT) is recommended in patients with ischemic stroke in the anterior and posterior circulation. Neurological outcomes due to posterior circulation strokes (PCS) without treatment remain poor. Our aim was to overview the literature on outcomes of IVT and conservative treatment in PCS, based on a systematic review and meta-analysis. MethodsA systematic literature search was performed on February 27th 2023. Outcome measures included favorable functional outcome at 90 days (modified Rankin Scale [mRS] 0-2), mortality at 90 days, and symptomatic intracranial hemorrhages (sICH). Weighted averages with DerSimonian-Laird approach was used to analyze the data. Subgroup analyses by time window were performed: standard time window (<4.5 hours after symptom onset) and extended time window (>4.5 hours). Analyses were performed using R. ResultsEight prospective and four retrospective cohort studies were included (n=1589 patients); no studies with conservative treatment were eligible. The pooled weighted probability regarding favorable functional outcome after IVT was 63% (95%CI:0.45-0.78), for mortality 19% (95%CI:0.11-0.30), and for sICH 4% (95%CI:0.02-0.07). Subgroup analyses showed higher probabilities on achieving favorable functional outcomes for patients treated in the standard (77%; 95%CI:0.62-0.88) compared to the extended time window (38%; 95%CI:0.29-0.48) with RR=1.93 (95%CI:1.66-2.24). Lower probabilities regarding mortality at 90 days and sICH were seen in patients treated in standard compared to extended time window (RR=0.42, 95%CI:0.34-0.51 and RR=0.27, 95%CI:0.16-0.45, respectively). ConclusionsIVT in patients with PCS seems to be safe and effective in standard and extended time window. The effect of IVT is higher in the standard time window.