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Background and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. Methods This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). Results Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

BackgroundHeterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20-25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults.MethodologyWe conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5-17 months in a highly endemic malaria transmission area of Burkina Faso.ResultsChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290-387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression.ConclusionsThis study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting.Trial registrationClinicalTrials.gov NCT01635647. Pactr.org PACTR201208000404131.

The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer's loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framework to two distinct high angular resolution diffusion-weighted imaging (HARDI) acquisition protocols on one cohort, comprised of ten healthy volunteers and five MS patients. The OR was successfully delineated in both HARDI acquisitions in the healthy volunteers and MS patients. Quantitative evaluation of the OR position was done by comparing the results with histological reference data. Compared with histological mask, the OR reconstruction into a template (OR-TCT) was highly precise (percentage of voxels within the OR-TCT correctly defined as OR), ranging from 0.71 to 0.83. The sensitivity (percentage of voxels in histological reference mask correctly defined as OR in OR-TCT) ranged from 0.65 to 0.81 and the accuracy (measured by F1 score) was 0.73 to 0.77 in healthy volunteers. When AEC was not applied the precision and accuracy decreased. The absolute agreement between both HARDI datasets measured by the intraclass correlation coefficient was 0.73. This improved framework allowed us to reconstruct the OR with high reliability and accuracy independently of the acquisition parameters. Moreover, the reconstruction was possible even in the presence of tissue damage due to MS. This framework could also be applied to other tracts with complex configuration.

O transplante renal é, atualmente, a melhor alternativa de tratamento para a doença renal crônica em estágio avançado. Melhorias na avaliação imunológica pré-transplante, como o emprego rotineiro de testes para identificação de anticorpos anti-HLA no soro do receptor, possibilitaram a identificação de pacientes com alto risco imunológico, com maior chance de rejeição ao enxerto e permitiram melhor alocação dos órgãos doados. Paralelamente, a disponibilidade de novas medicações imunossupressoras aumentou a gama de opções para o tratamento após o transplante. Esses dois fatores foram os responsáveis pelo grande sucesso dos programas de Transplante Renal em curto prazo, tornando possível o transplante entre indivíduos não aparentados com uma incidência de rejeição aguda satisfatória. No entanto, os resultados em longo prazo permanecem abaixo do desejado. Um dos principais problemas enfrentados pelo nefrologista atualmente é avaliar, de maneira confiável, o grau de imunossupressão de cada paciente. A reatividade imunológica contra o enxerto, presente em diferentes graus durante todo o período após o transplante, permanece pouco acessível pelos exames de rotina disponíveis. Os métodos diagnósticos atuais não são capazes de identificar as diferentes variações dessa reatividade, que é bastante heterogênea, compreendendo um amplo espectro que varia de rejeição a tolerância. Dessa forma, faz-se necessário o desenvolvimento de ensaios voltados para a monitorização imunológica após o transplante renal, os quais possibilitariam o diagnóstico precoce de eventos deletérios ao enxerto, além de melhor individualização da terapia imunossupressora.

Introdução: Tim-3 é uma proteína de membrana com função inibitória, presente em linfócitos Th1. Seu ligante recentemente identificado, a galectina-9, é expresso em alguns subtipos de linfócitos, e também pode ser induzido por citocinas inflamatórias em células endoteliais e fibroblastos. Juntamente com as células T CD4+CD25+, essas moléculas exercem uma função reguladora da resposta imune. O fator de transcrição FOXP3 está relacionado aos linfócitos T reguladores CD4+CD25+. Objetivo: Avaliar a presença de moléculas relacionadas à resposta imune reguladora intra-enxerto renal durante episódio de rejeição. Material e Métodos: Os níveis de RNA mensageiro para moléculas representativas da resposta imune reguladora (Tim-3, galectina-9 e FOXP3) e da resposta imune citotóxica (perforina, granzima B e interferon-γ) foram quantificados pelo método de reação em cadeia da polimerase em 24 amostras de produtos de enxertectomia, com os seguintes diagnósticos: rejeição aguda não-vascular (n=5), rejeição aguda vascular (n=14) e perda de causa não-imune (n=5, como controle). Resultados: A diferença encontrada entre as medianas dos grupos controle e de rejeição aguda vascular foi estatisticamente significante para todas as moléculas avaliadas: p=0,024 para galectina-9, p=0,008 para Tim3, p=0,005 para FOXP3, p=0,008 para perforina e interferon-γ, e p=0,003 para granzima B. Conclusão: Esse padrão sugere que o desenvolvimento da resposta imune é um evento dinâmico, com expressão de moléculas e recrutamento de células com funções diferentes, citopática e reguladora.