[Treatment of brain AVMS (TOBAS): A randomized controlled trial and registry]. / Le traitement des MAVS cérébrales (TOBAS) : une étude randomisée controlée avec registre.

OBJECTIVE: The management of unruptured and ruptured brain arteriovenous malformations (AVMs) remains controversial. The Treatment of Brain AVM Study (TOBAS) was designed to assess curative treatments in the management of AVMs. The purpose of our study is to provide a care trial context to brain AVM patients. METHODS: TOBAS is a pragmatic, prospective study including 2 randomized controlled trials and a registry. All AVM patients can be recruited. The preferred management modality will be predetermined prior to randomization by the team based on clinical judgment. Patients eligible for both conservative and interventional management will be randomly allocated conservative or curative treatment. Randomization will be stratified by a treatment modality (surgery, radiosurgery or embolization) and minimized according to a history of previous rupture and Spetzler-Martin grade. A second randomization will allocate eligible patients to embolization/no embolization prior to surgery or radiosurgery. The primary outcome of the study is death (any cause) or disabling stroke (mRS>2) at 10 years. All patients managed according to clinical judgment alone will be included in the registry. The study is registered under: wwwTrials.gov, ID: NCT02098252. EXPECTED RESULTS: A minimum recruitment of 540 patients is required to show that treatment can reduce the primary outcome by 10 % (from 25 to 15 %); 440 patients will be needed to show a 10 % increase in angiographic occlusion for a good clinical outcome with pre-embolization. CONCLUSION: The trial is designed to offer optimal and verifiable care to patients with brain AVMs in spite of the uncertainty. We are currently seeking the participation of multiple centers.

Susceptibility vessel sign on T2* magnetic resonance imaging and recanalization results of mechanical thrombectomy with stent retrievers: a multicentre cohort study.

BACKGROUND AND PURPOSE: The susceptibility vessel sign (SVS) on T2*-weighted magnetic resonance imaging has been reported in several studies as a negative predictor of early recanalization after intravenous thrombolysis. The meaning of SVS regarding the results of mechanical thrombectomy with stent retrievers was investigated. METHODS: Susceptibility vessel sign presence and length were studied in 153 acute ischaemic stroke patients (82 men; mean ± SD age 59 ± 17 years, baseline National Institutes of Health Stroke Scale score 17.2 ± 6.5) from three stroke centres, treated with either mechanical thrombectomy alone (n = 84) or bridging therapy (n = 69). Variables were compared between recanalizers, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b, and non-recanalizers (TICI<2b). RESULTS: The SVS was present in 113 (73.8%) patients. There was no association between the presence of SVS and recanalization, obtained in 86 (56.2%) patients, in the whole population [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.53-2.92, P = 0.84) and in treatment subgroups (bridging: OR = 0.91, 95% CI 0.29-2.87, P = 1.0; thrombectomy alone: OR = 1.85, 95% CI 0.48-7.16, P = 0.54). However, in SVS+ patients, recanalization decreased with SVS length (OR 0.94 for each additional mm, 95% CI 0.89-0.99; P = 0.02). CONCLUSIONS: The success of recanalization in acute stroke patients treated with stent retrievers was related to thrombus length but not to the presence of SVS.

Bet v 1--a Trojan horse for small ligands boosting allergic sensitization?

BACKGROUND: Birch pollen allergy represents the main cause of winter and spring pollinosis in the temperate climate zone of the northern hemisphere and sensitization towards Bet v 1, the major birch pollen allergen, affects over 100 million allergic patients. The major birch pollen allergen Bet v 1 has been described as promiscuous acceptor for a wide variety of hydrophobic ligands. OBJECTIVE: In search of intrinsic properties of Bet v 1, which account responsible for the high allergenic potential of the protein, we thought to investigate the effects of ligand-binding on immunogenic as well as allergenic properties. METHODS: As surrogate ligand of Bet v 1 sodium deoxycholate (DOC) was selected. Recombinant and natural Bet v 1 were characterised physico-chemically as well as immunologically in the presence or absence of DOC, and an animal model of allergic sensitization was established. Moreover, human IgE binding to Bet v 1 was analysed by nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Ligand-binding had an overall stabilizing effect on Bet v 1. This translated in a Th2 skewing of the immune response in a mouse model. Analyses of human IgE binding on Bet v 1 in mediator release assays revealed that ligand-bound allergen-induced degranulation at lower concentrations; however, in basophil activation tests with human basophils ligand-binding did not show this effect. For the first time, human IgE epitopes on Bet v 1 were determined using antibodies isolated from patients' sera. The IgE epitope mapping of Bet v 1 demonstrated the presence of multiple binding regions. CONCLUSIONS AND CLINICAL RELEVANCE: Deoxycholate binding stabilizes conformational IgE epitopes on Bet v 1; however, the epitopes themselves remain unaltered. Therefore, we speculate that humans are exposed to both ligand-bound and free Bet v 1 during sensitization, disclosing the ligand-binding cavity of the allergen as key structural element.

A cólera no Estado do Rio Grande do Norte--Brasil--perfil sorológico e de sensibilidade do Vibrio cholerae a diferentes antimicrobianos / Cholera in Rio Grande do Norte State--Brazil: sorology and sensitivity of Vibrio cholerae to different antimicrobials

PURPOSE: The emergence of multiple resistance to antimicrobials in Vibrio cholerae isolated in the state of Ceará, Brazil, alerted researchers in this area to the sensitivity to antimicrobials of strains isolated in Rio Grande do Norte (RN), Brazil. METHODS: One hundred and four strains of V. cholerae of human origin, isolated by Laboratório Central de Saúde Pública Dr. Almino Fernandes, were serologically typified and evaluated for in vitro sensitivity to eight antibiotics belonging to different groups (polymyxine, tetracycline, chloramphenicol, nitrofurantoin, sulphazotrin, pefloxacine, erythromycine, ampicillin). The strains were collected from patients suspected of contracting choleric diarrhea in the year 1999, in Natal/RN/Brazil. RESULTS: From the sample total, 100 were identified as V. cholerae, serogroup O:1, biotype El Tor, with 99 (95.3%) belonging to serovar Ogawa and only 1 (0.9%) to serovar Inaba. The 4 remaining were characterized as non O:1 V. cholerae, with 3 (2.9%) biochemically identified as Heiberg type I and 1 (0.9%) as type II. All the V. cholerae serogroup O:1 strains were sensitive to tetracycline, chloramphenicol, sulphazotrin, pefloxacine, erythromycine and resistant to polymyxine. In relation to nitrofurantoin, only 1 was sensitive. Only 1 was resistant to ampicillin. The non O:1 V. cholerae strains were resistant to polymyxine. CONCLUSIONS: The results showed sensitivity in 100% of the V. cholerae serogroup O:1 strains to tetracycline, an elective drug in the treatment of cholera, and an absence of multiple resistant strains in our environment. An interesting finding was the frequency of serovar Ogawa in 1999, considering the greater incidence of serovar Inaba in other years of cholera outbreaks in RN.