Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials

Background and objectivesSeveral randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs.MethodsA systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model.ResultsNine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0–1 at 90 days (RR = 1.03; 95% CI = 0.97–1.10; P-value = 0.359) and mRS 0–2 at 90 days (RR = 1.03; 95% CI = 0.87–1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0–1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0–2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81–1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75–1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0–1, mRS 0–2, sICH, and mortality) compared to alteplase.DiscussionBased on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS

Orbit image analysis machine learning software can be used for the histological quantification of acute ischemic stroke blood clots

Our aim was to assess the utility of a novel machine learning software (Orbit Image Analysis) in the histological quantification of acute ischemic stroke (AIS) clots. We analyzed 50 AIS blood clots retrieved using mechanical thrombectomy procedures. Following HandE staining, quantification of clot components was performed by two different methods: a pathologist using a reference standard method (Adobe Photoshop CC) and an experienced researcher using Orbit Image Analysis. Following quantification, the clots were categorized into 3 types: RBC dominant (\u3e/=60% RBCs), Mixed and Fibrin dominant ( \u3e /=60% Fibrin). Correlations between clot composition and Hounsfield Units density on Computed Tomography (CT) were assessed. There was a significant correlation between the components of clots as quantified by the Orbit Image Analysis algorithm and the reference standard approach (rho = 0.944**, p \u3c 0.001, n = 150). A significant relationship was found between clot composition (RBC-Rich, Mixed, Fibrin-Rich) and the presence of a Hyperdense artery sign using the algorithmic method (X2(2) = 6.712, p = 0.035*) but not using the reference standard method (X2(2) = 3.924, p = 0.141). Orbit Image Analysis machine learning software can be used for the histological quantification of AIS clots, reproducibly generating composition analyses similar to current reference standard methods

U937 cell apoptosis induced by arsenite is prevented by low concentrations of mitochondrial ascorbic acid with hardly any effect mediated by the cytosolic fraction of the vitamin

partially_open6noArsenite directly triggers cytochrome c and Smac/DIABLO release in mitochondria isolated from U937 cells. These effects were not observed in mitochondria pre-exposed for 15 min to 10 µM L-ascorbic acid (AA). In other experiments, intact cells treated for 24–72 h with arsenite were found to die by apoptosis through a mechanism involving mitochondrial permeability transition. Pre-exposure (15 min) to low micromolar concentrations of AA and dehydroascorbic acid (DHA), resulting in identical cytosolic levels of the vitamin, had a diverse impact on cell survival, as cytoprotection was only observed after treatment with AA. Also the mitochondrial accumulation of the vitamin was restricted to AA exposure. An additional indication linking cytoprotection to the mitochondrial fraction of the vitamin was obtained in experiments measuring susceptibility to arsenite in parallel with loss of mitochondrial and cytosolic AA at different times after vitamin exposure. Finally, we took advantage of our recent findings that DHA potently inhibits AA transport to demonstrate that DHA abolishes all the protective effects of AA, under the same conditions in which the mitochondrial accumulation of the vitamin is prevented without affecting the overall cellular accumulation of the vitamin.embargoed_20150323Andrea Guidarelli;Mara Fiorani;Catia Azzolini;Liana Cerioni;Maddalena Scotti;Orazio CantoniGuidarelli, Andrea; Fiorani, Mara; Catia, Azzolini; Cerioni, Liana; Scotti, Maddalena; Cantoni, Orazi

Impact of e-ASPECTS software on the performance of physicians compared to a consensus ground truth: a multi-reader, multi-case study

BackgroundThe Alberta Stroke Program Early CT Score (ASPECTS) is used to quantify the extent of injury to the brain following acute ischemic stroke (AIS) and to inform treatment decisions. The e-ASPECTS software uses artificial intelligence methods to automatically process non-contrast CT (NCCT) brain scans from patients with AIS affecting the middle cerebral artery (MCA) territory and generate an ASPECTS. This study aimed to evaluate the impact of e-ASPECTS (Brainomix, Oxford, UK) on the performance of US physicians compared to a consensus ground truth.MethodsThe study used a multi-reader, multi-case design. A total of 10 US board-certified physicians (neurologists and neuroradiologists) scored 54 NCCT brain scans of patients with AIS affecting the MCA territory. Each reader scored each scan on two occasions: once with and once without reference to the e-ASPECTS software, in random order. Agreement with a reference standard (expert consensus read with reference to follow-up imaging) was evaluated with and without software support.ResultsA comparison of the area under the curve (AUC) for each reader showed a significant improvement from 0.81 to 0.83 (p = 0.028) with the support of the e-ASPECTS tool. The agreement of reader ASPECTS scoring with the reference standard was improved with e-ASPECTS compared to unassisted reading of scans: Cohen's kappa improved from 0.60 to 0.65, and the case-based weighted Kappa improved from 0.70 to 0.81.ConclusionDecision support with the e-ASPECTS software significantly improves the accuracy of ASPECTS scoring, even by expert US neurologists and neuroradiologists

Delayed hemorrhagic complications after flow diversion for intracranial aneurysms: a literature overview

International audienc

Imaging Characteristics of Growing and Ruptured Vertebrobasilar Non-Saccular and Dolichoectatic Aneurysms

International audienc

First-line thrombectomy strategy for carotid terminus occlusions: A systematic review and meta-analysis

Background: Little research has focused on the performance of mechanical thrombectomy (MT) in carotid terminus occlusions (CTOs). Therefore, the best first-line thrombectomy strategy for CTOs remains unclear. Purpose: To compare the safety and efficacy outcomes of three first-line thrombectomy techniques in CTOs. Methods: A systematic literature search was conducted in Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, and Cochrane Central Register of Clinical Trials databases. Studies providing safety and efficacy outcomes for endovascular treatment of CTOs were included. Data regarding successful recanalization, functional independence, symptomatic intracranial hemorrhage (sICH), and first pass efficacy (FPE) were extracted from the included studies. A random-effects model was used to calculate prevalence rates and their corresponding 95% confidence intervals (CI), and subgroup analyses were performed to assess the impact of the initial MT technique on safety and efficacy outcomes. Results: Six studies with 524 patients were included. The overall successful recanalization rate was 85.84% (95% CI = 77.96–94.52), and subgroup analysis did not show a significant difference among the three first-line MT techniques. Overall rates of functional independence and FPE were 39.73% (95% CI = 32.95–47.89) and 32.09% (95% CI = 22.93–44.92), respectively. The combined stent retriever (SR) and aspiration (ASP) technique achieved significantly higher first-pass efficacy rates compared to SR or ASP alone. The overall sICH rate was 9.89% (95% CI = 4.88–20.07), and subgroup analysis did not demonstrate a significant difference across groups. The sICH rates of SR, ASP, and SR + ASP were 8.49% (95% CI = 1.76–40.93), 6.8% (95% CI = 4.59–10.09), and 7.12% (95% CI = 0.27–100), respectively. Conclusions: Our results support that MT is highly effective for CTOs with functional independence rates of 39%. Additionally, in our meta-analysis, the SR + ASP technique was associated significantly greater rates of FPE compared to SR or ASP alone, without an increase in sICH rates. Prospective, large-scale studies are necessary to determine the optimal first-line MT technique in the endovascular treatment of CTOs

Hemodynamic Analysis of Fast and Slow Aneurysm Occlusions By Flow Diversion in Rabbits

Purpose: To assess hemodynamic differences between aneurysms that occlude rapidly and those occluding in delayed fashion after flow diversion in rabbits. Methods: Thirty-six elastase-induced aneurysms in rabbits were treated with flow diverting devices. Aneurysm occlusion was assessed angiographically immediately before they were sacrificed at 1 (n=6), 2 (n=4), 4 (n=8) or 8 weeks (n=18) after treatment. The aneurysms were classified into a fast occlusion group if they were completely or near completely occluded at 4 weeks or earlier and a slow occlusion group if they remained incompletely occluded at 8 weeks. The immediate post-treatment flow conditions in aneurysms of each group were quantified using subject-specific computational fluid dynamics and statistically compared. Results: Nine aneurysms were classified into the fast occlusion group and six into the slow occlusion group. Aneurysms in the fast occlusion group were on average significantly smaller (fast=0.9 cm, slow=1.393 cm, p=0.024) and had smaller ostia (fast=0.144 cm2, slow=0.365 cm2, p=0.015) than aneurysms in the slow occlusion group. They also had a lower mean posttreatment inflow rate (fast=0.047 mL/s, slow=0.155 mL/s, p=0.0239), kinetic energy (fast=0.519 erg, slow=1.283 erg, p=0.0468), and velocity (fast=0.221 cm/s, slow=0.506 cm/s, p=0.0582). However, the differences in the latter two variables were only marginally significant. Conclusions: Hemodynamic conditions after flow diversion treatment of cerebral aneurysms in rabbits are associated with the subsequent aneurysm occlusion time. Specifically, smaller inflow rate, kinetic energy, and velocity seem to promote faster occlusions, especially in smaller and small-necked aneurysms. These results are consistent with previous studies based on clinical series