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Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Background Flow diversion (FD) has emerged as an effective treatment option for intracranial aneurysms. However, there is limited evidence regarding its safety and efficacy specifically for distal and small‐artery aneurysms of the posterior circulation. This study aimed to investigate the outcomes of FD for aneurysms arising from the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and the P2 and P3 segments of the posterior cerebral artery. Methods This is a subanalysis of the Post‐FD (Posterior Circulation Aneurysms Treated With Flow Diversion) registry, highlighting distal aneurysms in the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and the P2 and P3 segments of the posterior cerebral artery treated with FD. Aneurysm characteristics and patient outcomes were described for the total series, and a more focused analysis comparing fusiform/dissecting versus saccular aneurysms was performed. The primary treatment outcome was complete aneurysm occlusion (Raymond–Roy class 1). Primary safety outcome was major ischemic/hemorrhagic stroke following FD. Secondary outcomes included functional outcome, aneurysm retreatment, and in‐stent stenosis. Results Overall, 36 patients with 36 aneurysms were treated with FD, with a median age of 60.0 years (interquartile range [IQR], 52.8—65.3 years). Of those, 13 were fusiform/dissecting, while 23 were saccular aneurysms. Complete occlusion was achieved in 78.1% for all aneurysms at a median follow‐up of 14.0 months (IQR, 9.3–48.6 months). There was a nonsignificant trend in rates of complete occlusion between fusiform/dissecting (91.7%) and saccular aneurysms (70%; P = 0.151). Major stroke was reported in 2 cases (5.6%) and in‐stent stenosis in 4 (11.1%), and retreatment was required for 4 aneurysms (11.4%) There was no difference in rates of major stroke, in‐stent stenosis, or retreatment between fusiform/dissecting and saccular aneurysms. Conclusion This study suggests the safety and feasibility of FD for distal aneurysms of the posterior circulation, particularly fusiform/dissecting aneurysms. Further larger‐scale studies are warranted to confirm these findings.

Abstract Background The management of hemostasis in patients medicated with apixaban (Eliquis) undergoing emergency cardiac surgery is exceedingly difficult. The body’s natural elimination pathways for apixaban prove ineffective in emergency situations, and the impact of hemodialysis is limited. The application of Cytosorb® may attenuate the concentration of apixaban, thereby facilitating the stabilization of these patients. Case presentation An 84-year-old man treated with apixaban, underwent emergency ascending aorta replacement surgery due to an acute type A aortic dissection. To address the challenges induced by apixaban, we integrated Cytosorb® cartridge into the Cardiopulmonary bypass circuit. There was a 63.7% decrease in perioperative apixaban-specific anti-factor Xa activity. The patient’s postoperative course was favourable. Conclusion Hemoadsorption with Cytosorb® may offers a safe and feasible approach for reducing apixaban concentration in emergency cardiac surgery, thereby mitigating the risk of hemorrhagic complications.

Abstract Background Management of pediatric stroke is challenging because of the paucity of data supporting the efficacy of interventions. This scoping review details the treatments available for the acute phase of stroke in pediatric patients with arterial ischemic stroke. Summary of Review Overall, 68 relevant articles were published between 2001 and 2023. The primary study included 48 case reports (n = 48). Eleven articles reported the use of intravenous thrombolysis (IVT) with alteplase, eight used intra‐arterial (IA) alteplase, and 52 reported mechanical thrombectomy (MT). IVT was administered to 195 patients with a median of 5.5 h of stroke onset, and only four (2.0%) had intracranial hemorrhage after alteplase treatment. Of the 11 articles, nine used 0.9 mg/kg IVT administered as a 10% bolus, with the remaining 90% administered over one hour, and one study used 0.54 mg/kg. IA was performed in 17 patients with a median of 5.05 h of stroke onset, and three individuals (17.6%) had intracranial hemorrhage. Of the eight reports that document IA, two used 0.9 mg/kg; one each used 0.16 mg/kg, 0.1 mg/kg, 0.6 mg/kg, 100 mg/day, and 10 mg/day; and one article documented the use of urokinase 750 000 IU. MT was used in 434 and 215 individuals in a previous systematic review, with a median of 11.82 h of stroke onset, and only 2.9% had intracranial hemorrhage after the treatment. Stent retrievers were used in 33 reports (63.5%) and aspiration retrievers were mentioned in 15 articles (28.8%). Overall, the outcomes ranged from complete to moderate recovery for all modalities. Conclusions IVT and MT are safer than IA; however, despite the lack of clinical trials, all modalities seem effective in improving clinical recovery. To guide clinical practice and determine better intervention modalities, clinicians should note the key messages from this review, such as using magnetic resonance imaging in the acute phase and identifying key risk factors and presenting symptoms.

Background Large‐vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood‐based biomarkers (glial fibrillary acidic protein and d‐dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance‐identified stroke code activations

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Objective Selected patients with large vessel occlusion (LVO) strokes can benefit from endovascular therapy (EVT). However, the effectiveness of EVT is largely dependent on how quickly the patient receives treatment. Recent technological developments have led to the first neurointerventional treatments using robotic assistance, opening up the possibility of performing remote stroke interventions. Existing telestroke networks provide acute stroke care, including remote administration of intravenous thrombolysis (IVT). Therefore, the introduction of remote EVT in distant stroke centers requires an adaptation of the existing telestroke networks. The aim of this work was to propose a framework for centers that are potential candidates for telerobotics according to the resources currently available in these centers. Methods In this paper, we highlight the future challenges for including remote robotics in telestroke networks. A literature review provides potential solutions. Results Existing telestroke networks need to determine which centers to prioritize for remote robotic technologies based on objective criteria and cost-effectiveness analysis. Organizational challenges include regional coordination and specific protocols. Technological challenges mainly concern telecommunication networks. Conclusions Specific adaptations will be necessary if regional telestroke networks are to include remote robotics. Some of these can already be put in place, which could greatly help the future implementation of the technology.

The management of unruptured brain arteriovenous malformations (ubAVMs) is a complex challenge to neurovascular practitioners. This meta-analysis aimed to identify the optimal management of ubAVMs comparing conservative management, embolization, radiosurgery, microsurgical resection, and multimodality. The search strategy was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Ovid Medline, Embase, Web of Science, and Cochrane Library databases to identify relevant papers. Using R version 4.1.1., a frequentist network meta-analysis was conducted to compare different management modalities for the ubAVMs. Overall, the conservative group had the lowest risk of rupture (P-score=0.77), and the lowest rate of complications was found in the conservative group (P-score=1). Among different interventions, the multimodality group had the highest rupture risk (P-score=0.34), the lowest overall complications (P-score=0.75), the best functional improvement (P-score=0.65), and the lowest overall mortality (P-score=0.8). However, multimodality treatment showed a significantly higher risk of rupture (odds ratio [OR]=2.13; 95% confidence interval [95% CI]=1.18–3.86) and overall complication rate (OR=5.56; 95% CI=3.37–9.15) compared to conservative management; nevertheless, there were no significant differences in overall mortality or functional independence when considered independently. Conservative management is associated with the lowest rupture risk and complication rate overall. A multimodal approach is the best option when considering mortality rates and functional improvement in the context of existing morbidity/symptoms. Microsurgery, embolization, and radiosurgery alone are similar to the natural history in terms of functional improvement and mortality, but have higher complication rates.

BackgroundGuidelines recommend the use of perfusion computed tomography (CT) to identify emergent large vessel ischemic stroke (ELVIS) patients who are likely to benefit from endovascular thrombectomy (EVT) if they present within 6-24 hour (late window) of stroke onset. We aim to determine if the interrater and intrarater reliability among physicians when recommending EVT is significantly different when perfusion CT or non-perfusion CT is reviewed.MethodsA total of 30 non-consecutive patients will be selected from our institutional database comprising 3144 cranial CT scans performed for acute stroke symptoms January 2018 to August 2022. The clinical and radiologic data of the 30 patients will be presented in random order to a group of 29 physicians in two separate sessions at least three weeks apart. In each session, the physicians will evaluate each patient once with automated perfusion images and once without. We will use non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG).DiscussionThe results obtained from this study, combined with the clinical outcomes data of patients categorized through the two imaging techniques and a cost-effectiveness analysis, will offer a comprehensive evaluation of the clinical utility of perfusion CT neuroimaging. Should there be no significant disparity in the reliability of decisions made by clinicians using the two neuroimaging protocols, it may be necessary to revise existing recommendations regarding neuroimaging in the later time window to align with these findings.

Background For acute proximal intracranial artery occlusions, contact aspiration may be more effective than stent‐retriever for first‐line reperfusion therapy. Due to the lack of data regarding medium vessel occlusion thrombectomy, we evaluated outcomes according to first‐line technique in a large, multicenter registry. Methods Imaging, procedural, and clinical outcomes of patients with acute proximal medium vessel occlusions (M2, A1, or P1) or distal medium vessel occlusions (M3, A2, P2, or further) treated at 37 sites in 10 countries were analyzed according to first‐line endovascular technique (stent‐retriever versus aspiration). Multivariable logistic regression and propensity‐score matching were used to estimate the odds of the primary outcome, expanded Thrombolysis in Cerebral Infarction score of 2b–3 (“successful recanalization”), as well as secondary outcomes (first‐pass effect, expanded Thrombolysis in Cerebral Infarction 2c‐3, intracerebral hemorrhage, and 90‐day modified Rankin scale, 90‐day mortality) between treatment groups. Results Of the 440 included patients (44.5% stent‐retriever versus 55.5% aspiration), those treated with stent‐retriever had lower baseline Alberta Stroke Program Early Computed Tomography Scale scores (median 8 versus 9; P

Introduction Flow diverters (FD) have become a revolutionary approach in the endovascular treatment of intracranial aneurysms (IAs), supplanting traditional methods (1). Despite their demonstrated efficacy and safety, unforeseeable device‐related technical complications, such as fish‐mouthing, device braid narrowing, deformation, ovalization, and collapsing have been reported during implantation and follow‐up (2,3,4). However, the definitions and reporting of these complications remain inconsistent. We conducted a systematic review and meta‐analysis to assess overall device‐related technical complication rates associated with flow diversion and provide an overview of the current reported definitions. Methods We searched six databases up to April 4th, 2023, and included studies that reported device‐related technical complications related to FD treatment for IAs. We considered five main outcome measures as device‐related technical complications: (1) fish‐mouthing, (2) device braid collapsing, (3) device braid narrowing, (4) device braid deformation, and (5) device braid ovalization. The data from these studies were pooled using a random‐effects model. Results We included 48 studies involving 3,572 patients and 3,939 aneurysms. Among them, 14 studies (39%) provided definitions for fish‐mouthing. However, none of the included studies offered specific definitions for device braid collapsing, narrowing, or deformation, despite reporting rates for these complications in five, six, and three studies, respectively. The pooled rates for device‐related technical complications were as follows: 3% (95% CI 2 – 4%; I2 = 27%) for fish‐mouthing, 1% (95% CI 0 – 3%; I2 = 0%) for collapsing, 7% (95% CI 2 – 20%; I2 = 85%) for narrowing, and 1% (95% CI 1 – 4%; I2 = 0%) for deformation. Device braid ovalization data were not available. Conclusion The findings of this study suggest that FD treatment for IAs generally exhibits low rates of fish‐mouthing, device braid narrowing, collapsing, and deformation. However, the lack of standardized definitions hinders the ability to objectively compare device outcomes, emphasizing the need for uniform device‐related complication definitions in future prospective studies on FD.

Large clinical trials have helped establish the benefit of endovascular treatment (EVT) in patients with acute ischemic stroke with large vessel occlusion and small infarct core volume as determined by scores ≥6 on the Alberta Stroke Program Early CT Scores. Several small studies have suggested that patients with large infarct core volume (LICV) may also benefit from EVT. Currently, at least 6 randomized clinical trials are examining the benefit of extending EVT to this population of patients with acute ischemic stroke. These trials were independently conceived and have significant differences in their inclusion criteria. Understanding these inclusion criteria and other differences in trial design is pivotal for the field to interpret the upcoming results of these trials. In this review, the designs of the 6 trials are summarized and compared. Specific differences are described, including (1) the rationale for EVT treatment in patients with LICV, (2) how to define LICV and the imaging modality used to identify LICV, (3) inclusion of an Alberta Stroke Program Early CT Score 0 to 5 versus 3 to 5, (4) use of the mismatch between blood flow and the size of infarct as an inclusion criterion, and (5) inclusion of early window and/or late window patients. The potential impact of these trial results on current guidelines for acute ischemic stroke is discussed. Differences in trial design as well as inclusion and exclusion criteria may influence trial outcomes. The implications of these trial results will likely be enhanced by a pooled analysis.

Background and purpose40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome.Materials and MethodsMulticentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0–2).ResultsIn the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02–1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27–3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41–1.24]) nor bridging IVT (aOR 1.08 [0.67–1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24–2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92).ConclusionBridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT.Registrationclinicaltrials.gov; Unique identifier: NCT03496064.

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

The bifunctional enzyme CoaBC catalyses the second and third step in the Coenzyme A (CoA) biosynthesis pathway and is of interest as a M. tuberculosis drug target. Here, the authors present the full-length crystal structure of Mycobacterium smegmatis CoaBC, which is regulated by CoA and CoA thioesters and forms a dodecamer and by performing a high-throughput screen they identify selective inhibitors of M. tuberculosis CoaB that bind to an allosteric site within CoaB.

Este artigo objetivou estudar a relação existente entre a utilização de elementos de jogos e a motivação dos estudantes para participar de atividades acadêmicas que exijam uma postura ativa. Através de uma abordagem qualitativa, foi analisada uma universidade que reformou um evento acadêmico inserindo elementos de jogos (gamificação). Um dos resultados obtidos indica que grande parte dos alunos avaliaram positivamente a iniciativa, afirmando que houve um aumento em sua motivação. Também foi possível avaliar, neste caso, quais elementos de jogos estão mais relacionados com as motivações intrínseca e extrínseca. Além disso, foram apontados alguns problemas organizacionais que podem ter influenciado na motivação dos participantes durante o evento. Por fim, espera-se que este artigo possa levantar reflexões práticas quanto ao uso da gamificação em eventos acadêmicos.

Introduction: The ANGEL‐ASPECT trial (NCT 04551664) is an ongoing, multicenter, randomized controlled trial (RCT) currently being conducted in China. The goal of ANGEL‐ASPECT’s is to include the maximum patients with a true large core for whom EVT is not recommended under current guidelines with level 1 evidence. By enrolling patients with ASPECTS 70 cc, ANGEL‐ASPECT maximizes the inclusion of patients with true large cores. What’s more, intracranial atherosclerotic disease (ICAD) is common in the Asian population while most of the previous trials have been performed in the Western world where ICAD is less prevalent. Methods: We reviewed the merits of ANGEL‐ASPECT’s design and suggest that it be included in the discussion of patient selection criteria in large core trials. Results: The primary goal of our trial is to determine whether EVT will benefit or harm AIS patients with LVO and a “large core” infarct. The inclusion criteria for ANGEL‐ASPECT are: 1. If ASPECTS is 3–5 and presentation is within 24 hours of onset, patients are enrolled without obtaining CTP. 2. If ASPECTS is >5 and presentation is beyond 6 hours of onset, only patients with relative cerebral blood flow (rCBF) of < 30% by CTP or apparent diffusion coefficient (ADC) of < 620 on MRI and estimated core volume of 70–100 cc are enrolled. 3. If ASPECTS is

Este artigo objetivou estudar a relação existente entre a utilização de elementos de jogos e a motivação dos estudantes para participar de atividades acadêmicas que exijam uma postura ativa. Através de uma abordagem qualitativa, foi analisada uma universidade que reformou um evento acadêmico inserindo elementos de jogos (gamificação). Um dos resultados obtidos indica que grande parte dos alunos avaliaram positivamente a iniciativa, afirmando que houve um aumento em sua motivação. Também foi possível avaliar, neste caso, quais elementos de jogos estão mais relacionados com as motivações intrínseca e extrínseca. Além disso, foram apontados alguns problemas organizacionais que podem ter influenciado na motivação dos participantes durante o evento. Por fim, espera-se que este artigo possa levantar reflexões práticas quanto ao uso da gamificação em eventos acadêmicos.

Background and purpose: In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. Methods: Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0–180 min ( n = 192), 180–360 min ( n = 876) and >360 min ( n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0–2) at day 90. Results: Every hour delay in TTR was a significant factor related to mRS 0–2 (aOR 0.933, 95% CI 0.887–0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0–1 (aOR 0.929, 95% CI 0.877–0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. Conclusions: TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways.

RESUMO Objetivo: Determinar o desempenho da dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel quando da alta da unidade de terapia intensiva para predição da mortalidade após permanência na mesma unidade. Métodos: Durante 24 meses conduziu-se um estudo prospectivo observacional de coorte em uma unidade de terapia intensiva polivalente de oito leitos. Colheram-se os seguintes dados: APACHE II, SOFA, níveis de proteína C-reativa e receptor ativador de plasminogênio tipo uroquinase solúvel, além de contagem de leucócitos no dia da alta da unidade de terapia intensiva, em pacientes que sobreviveram à permanência na unidade de terapia intensiva. Resultados: Durante este período, incluíram-se no estudo 202 pacientes; 29 (18,6%) morreram após alta da unidade de terapia intensiva. Os não sobreviventes eram mais idosos e tinham enfermidades mais graves quando admitidos à unidade de terapia intensiva, com escores de severidade mais elevados, e necessitaram de vasopressores por mais tempo do que os que sobreviveram. As áreas sob a curva Característica de Operação do Receptor para SOFA, APACHE II, proteína C-reativa, contagem de leucócitos e receptor ativador de plasminogênio tipo uroquinase solúvel, no momento da alta da unidade de terapia intensiva, avaliadas como marcadores de prognóstico de morte hospitalar, foram, respectivamente, 0,78 (IC95% 0,70 - 0,86); 0,70 (IC95% 0,61 - 0,79); 0,54 (IC95% 0,42 - 0,65); 0,48 (IC95% 0,36 - 0,58); 0,68 (IC95% 0,58 - 0,78). O SOFA associou-se de forma independente com risco mais elevado de morte no hospital (OR 1,673; IC95% 1,252 - 2,234), assim como para mortalidade após 28 dias (OR 1,861; IC95% 1,856 - 2,555) e mortalidade após 90 dias (OR 1,584; IC95% 1,241 - 2,022). Conclusão: A dosagem do receptor ativador de plasminogênio tipo uroquinase solúvel na alta unidade de terapia intensiva teve um valor prognóstico fraco de mortalidade após a permanência nesta unidade.

Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the treatment of tuberculosis. However, the absence of defined molecular targets and modes of action could lead to failure in drug development. Therefore, a combination of ligand-based and structure-based chemogenomic approaches followed by biophysical and biochemical validation have been used to identify targets for Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA as targets for several hits, with some showing dual activity against these proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50 μM against M. tuberculosis EthR and three were confirmed to be also simultaneously active against InhA. Further hit validation was performed using X-ray crystallography yielding eight new crystal structures of EthR inhibitors. Although the EthR inhibitors attain their activity against M. tuberculosis by hitting yet undefined targets, these results provide new lead compounds that could be further developed to be used to potentiate the effect of EthA activated pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.

BackgroundThe pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale.MethodsPREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated.ResultsAs per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series.ConclusionsThe PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture.Trial registrationNCT02186561.

We investigated the flow modifications induced by a large panel of commercial-off-the-shelf (COTS) intracranial stents in an idealized sidewall intracranial aneurysm (IA). Flow velocities in IA silicone model were assessed with and without stent implantation using particle imaging velocimetry (PIV). The use of the recently developed multi-time-lag method has allowed for uniform and precise measurements of both high and low velocities at IA neck and dome, respectively. Flow modification analysis of both regular (RSs) and flow diverter stents (FDSs) was subsequently correlated with relevant geometrical stent parameters. Flow reduction was found to be highly sensitive to stent porosity variations for regular stents RSs and moderately sensitive for FDSs. Consequently, two distinct IA flow change trends, with velocity reductions up to 50% and 90%, were identified for high-porosity RS and low-porosity FDS, respectively. The intermediate porosity (88%) regular braided stent provided the limit at which the transition in flow change trend occurred with a flow reduction of 84%. This transition occurred with decreasing stent porosity, as the driving force in IA neck changed from shear stress to differential pressure. Therefore, these results suggest that stents with intermediate porosities could possibly provide similar flow change patterns to FDS, favourable to curative thrombogenesis in IAs.

Introduction. Calcium channel blockers (CCBs) drugs are widely used in the treatment of cardiovascular diseases. CCB poisoning is associated with significant cardiovascular toxicity and is potentially fatal. Currently, there is no specific antidote and the treatment of CCB poisoning is supportive; however, this supportive therapy is often insufficient. We present a clinical case of severe diltiazem poisoning and the therapeutic approaches that were used. Case Report. A 55-year-old male was admitted to the intensive care unit (ICU) after voluntary multiple drug intake, including extended release diltiazem (7200 mg). The patient developed symptoms of refractory shock to conventional therapy and required mechanical ventilation, a temporary pacemaker, and renal replacement therapy. Approximately 17 hours after drug intake, hyperinsulinaemia-euglycaemia with lipid emulsion therapy was initiated, followed by progressive haemodynamic recovery within approximately 30 minutes. The toxicological serum analysis 12 h after drug ingestion revealed a diltiazem serum level of 4778 ng/mL (therapeutic level: 40–200 ng/mL). Conclusions. This case report supports the therapeutic efficacy of hyperinsulinaemia-euglycaemia and lipid emulsion in the treatment of severe diltiazem poisoning.

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p

Brazilian Cerrado is recognised as a biodiversity hotspot due to the presence of endemic species with great biological potential. Particularly, Lomatozona artemisiifolia, is a rare species found in the Cerrado region in midwestern Brazil. Efforts have been made for its conservation in the Cerrado, such as the use of in vitro micropropagation, demanding a comparative analysis between grown plants and those collected from nature. For this purpose, we performed the chemical study of L. artemisiifolia by LC-ESI-MS/MS and molecular networking analysis in the Global Natural Products Social Molecular Networking (GNPS) with in silico annotation using Network Annotation Propagation (NAP), which led to the observation of labdane diterpenes and flavonoid subclasses as the most representative specialised metabolites of this plant. In addition, molecular networking and chemometric analysis were correlated, allowing the metabolite profile emerging from field growth and micropropagation conditions to be observed. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of evidence of flow diversion (FD) safety for aneurysms treatment beyond the circle of Willis. Therefore, we provide a single-center real-world experience with the Silk Vista Baby (SVB). Methods: A single-center database was retrospectively reviewed for aneurysms treated with SVB flow diverters. Demographic information, clinical presentation, radiographic characteristics, procedural complications, and outcomes were assessed. Results: About 57 patients (66.7% female, mean age 54.3 ± 13.2) encompassing 57 aneurysms were included. Overall, 40.4% were ruptured: 68.4% saccular, 17.5% blister, 8.7% fusiform, and 5.3% dissecting. The majority were in the anterior circulation (68.4%), and in 48.2% of cases, the distal vessel diameter was inferior to 2 mm. The symptomatic ischemic rate was 5.2%, with one case due to in-stent thrombosis (1.8%). There were no hemorrhagic complications. Complication rates did not differ between ruptured and unruptured lesions (p = 0.356). There were no cases of delayed aneurysm rupture, and overall mortality was 1.8%. The median follow-up time was 18 ± 12 months. In-stent stenosis rate was 10.5% (6/57), all of which were asymptomatic. At the last follow-up, 70.2% of cases had an adequate occlusion (OKM C and D), and 96.5% had an mRS of 0–2. Conclusion: In our series, SVB was shown to be a safe device in the treatment of not only distal anterior circulation aneurysms but also in the management of complex posterior fossa and ruptured blister aneurysms. Multicenter studies are needed to confirm and generalize these results. [ABSTRACT FROM AUTHOR]