Frequency and predictors of symptomatic intracranial hemorrhage after intravenous thrombolysis for acute ischemic stroke in a Brazilian public hospital

OBJECTIVE: Scarce data are available on the occurrence of symptomatic intracranial hemorrhage related to intravenous thrombolysis for acute stroke in South America. We aimed to address the frequency and clinical predictors of symptomatic intracranial hemorrhage after stroke thrombolysis at our tertiary emergency unit in Brazil. METHOD: We reviewed the clinical and radiological data of 117 consecutive acute ischemic stroke patients treated with intravenous thrombolysis in our hospital between May 2001 and April 2010. We compared our results with those of the Safe Implementation of Thrombolysis in Stroke registry. Univariate and multiple regression analyses were performed to identify factors associated with symptomatic intracranial transformation. RESULTS: In total, 113 cases from the initial sample were analyzed. The median National Institutes of Health Stroke Scale score was 16 (interquartile range: 10-20). The median onset-to-treatment time was 188 minutes (interquartile range: 155-227). There were seven symptomatic intracranial hemorrhages (6.2%; Safe Implementation of Thrombolysis in Stroke registry: 4.9%; p = 0.505). In the univariate analysis, current statin treatment and elevated National Institute of Health Stroke Scale scores were related to symptomatic intracranial hemorrhage. After the multivariate analysis, current statin treatment was the only factor independently associated with symptomatic intracranial hemorrhage. CONCLUSIONS: In this series of Brazilian patients with severe strokes treated with intravenous thrombolysis in a public university hospital at a late treatment window, we found no increase in the rate of symptomatic intracranial hemorrhage. Additional studies are necessary to clarify the possible association between statins and the risk of symptomatic intracranial hemorrhage after stroke thrombolysis

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Background and purpose Functional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke.Methods A retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K-2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K-2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score <2) were performed.Results 105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K-2 coefficient (1027.4 vs 692.7x10(-6)/s; p=0.006). In women, atrial fibrillation (beta=583.6; p=0.04) and increasing NAWM ADC (beta=4.4; p=0.02) were associated with increased NAWM K-2 coefficient. In multivariable regression analysis, the K-2 coefficient was an independent predictor of DWI volume in women (beta=0.007; p=0.01) but not men.Conclusions In women with acute ischaemic stroke, increased NAWM K-2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed

Outcomes of carotid artery stenting at a high-volume Brazilian interventional neuroradiology center

OBJECTIVES: Carotid artery stenting is an emerging revascularization alternative to carotid endarterectomy. However, guidelines have recommended carotid artery stenting only if the rate of periprocedural stroke or death is < 6% among symptomatic patients and < 3% among asymptomatic patients. The aim of this study is to evaluate and compare clinical outcomes of symptomatic and asymptomatic patients who had undergone carotid artery stenting as a first-intention treatment. METHOD: A retrospective analysis of patients who underwent carotid artery stenting by our interventional neuroradiology team was conducted. Patients were divided into two groups: symptomatic and asymptomatic patients. The primary endpoints were ipsilateral ischemic stroke, ipsilateral parenchymal hemorrhage and major adverse cardiac and cerebrovascular events at 30 days. The secondary endpoints included ipsilateral ischemic stroke, ipsilateral parenchymal hemorrhage, ipsilateral transient ischemic attack and major adverse cardiac and cerebrovascular events between the 1- and 12-month follow-ups. RESULTS: A total of 200 consecutive patients were evaluated. The primary endpoints obtained in the symptomatic vs. asymptomatic groups were ipsilateral stroke (2.4% vs. 2.7%, p = 1.00), ipsilateral parenchymal hemorrhage (0.8% vs. 0.0%, p = 1.00) and major adverse cardiac and cerebrovascular events (4.7% vs. 2.7%, p = 0.71). The secondary endpoints obtained in the symptomatic vs. asymptomatic groups were ipsilateral ischemic stroke (0.0% vs. 0.0%), ipsilateral parenchymal hemorrhage (0.0% vs. 0.0%), ipsilateral TIA (0.0% vs. 0.0%, p = 1.00) and major adverse cardiac and cerebrovascular events (11.2% vs. 4.1%, p = 0.11). CONCLUSIONS: In this retrospective study, carotid artery stenting was similarly safe and effective when performed as a first-intention treatment in both symptomatic and asymptomatic patients. The study results comply with the safety requirements from current recommendations to perform carotid artery stenting as an alternative treatment to carotid endarterectomy

Intravenous thrombolysis for acute ischemic stroke at a brazilian, public and academic hospital

INTRODUÇÃO E OBJETIVOS. O acidente vascular cerebral (AVC) é uma das principais causas de incapacidade no mundo, e é a principal causa de morte no Brasil. Atualmente, o único tratamento clínico para o AVC é a trombólise intravenosa com o ativador de plasminogênio tecidual recombinante. Este tratamento não é isento de complicações, e é necessária a adesão rigorosa a protocolos de tratamento. Por isso, sua disseminação no mundo foi condicionada à realização de estudos de fase 4 em diversos países, especialmente voltados para averiguar desfechos eficácia e segurança. Recentemente, tem havido esforços para disseminar o uso de terapia trombolítica para o AVC no Brasil. Entretanto, são escassos os dados sobre a aplicação deste tratamento no nosso país. Este estudo pretendeu relatar a experiência com este tratamento no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto um hospital terciário, público, universitário, que recebe pacientes encaminhados por um sistema de regulação médica do Sistema Único de Saúde , e comparar nossa casuística com aquela do um dos maiores estudos de fase 4 sobre este tema (Safe Implementation of Thrombolysis for Stroke, SITS). MÉTODOS. Trata-se de um estudo observacional, retrospectivo, baseado em revisão de registros hospitalares, da casuística de pacientes com AVC tratados com trombólise intravenosa no nosso hospital. O desfecho primário de interesse foi a ocorrência de transformação hemorrágica sintomática (THS). Foram descritas características demográficas, comorbidades, uso prévio de medicações, gravidade clínica do AVC e períodos entre início dos sintomas, admissão e tratamento. RESULTADOS. Estudamos 209 pacientes com AVC tratados em nosso centro. Verificamos que estes pacientes apresentaram elevada frequência de comorbidades e défices neurológicos mais graves, e receberam tratamento mais tardiamente quando comparados à população do estudo SITS. A pontuação mediana na escala National Institutes of Health Stroke Scale foi de 14 (intervalo interquartil: 9 a 19), e a mediana do período entre o início dos sintomas e o tratamento foi de 200 minutos (intervalo interquartil: 165 a 247). Ao longo dos anos observamos um aumento do número de pacientes tratados em janelas tardias e da proporção de pacientes tratados em até 60 minutos da admissão. Observamos 16 THS (7,7%), frequência similar àquela descrita no ensaio SITS (4,7%; P=0,09). Na análise univariada, a ocorrência de THS esteve associada à gravidade clínica do AVC, ao período sintoma-agulha e ao uso prévio de estatinas. Em análise multivariada, a gravidade clínica do AVC e o uso prévio de estatinas foram preditores independentes de THS. CONCLUSÕES. A trombólise intravenosa para o AVC foi aplicada de forma segura em um hospital brasileiro, público e acadêmico, embora em uma casuística de pacientes com elevada frequência de comorbidades, quadros clínicos mais graves e janelas terapêuticas mais tardias em comparação com aquelas descritas em casuísticas de países desenvolvidos. São necessários aprimoramentos do fluxo de encaminhamento de pacientes com AVC agudo, com qualificação do atendimento pré-hospitalar e do sistema e regulação médica, com o objetivo de reduzir o tempo para chegada ao hospital e de ampliar o acesso à terapia trombolítica para todo o espectro de pacientes com AVC. A gravidade clínica do AVC e o uso prévio de estatinas parecem estar associados a maior chance de transformação hemorrágica sintomática relacionada à trombólise intravenosa.BACKGROUND AND AIMS. Stroke is one of the leading causes of disability in the world, and is the leading cause of death in Brazil. Intravenous thrombolysis with tissue plasminogen activator is the only treatment for stroke with proved benefit. Intravenous thrombolysis is associated with significant risks, and strict adherence to treatment protocols is necessary. The dissemination of this treatment has been conditioned in many countries to the conduction of phase 4 studies, specifically designed to verify safety outcome measures. Recently, there has been important initiatives for the national dissemination of intravenous thrombolysis in Brazil. Nevertheless, there is scarce data about the use of this treatment in our country. This study aimed to describe one decade of experience with intravenous thrombolysis for stroke in our institution, and to compare our sample with one of the largest international phase 4 stroke registry on stroke thrombolysis (Safe Implementation of Thrombolysis for Stroke, SITS). METHODS. This is an observational, retrospective study, involving all patients treated with intravenous thrombolysis for acute stroke at our hospital. The primary endpoints were symptomatic intracranial hemorrhage and in-hospital death. We also describe the demographics, medical history, clinical severeness and the timeline from symptom onset to treatment. RESULTS. We studied 209 patients with acute stroke treated with intravenous thrombolysis at our institution. We found a severe clinical profile, with more frequent comorbidities, more severe neurological deficits and a rather late treatment window, when compared with the SITS registry. Median NIHSS score was 14 (interquartile range: 9 a 19). Median onset-to-treatment time was 200 minutes (interquartile range: 165 a 247). Through the study period, the number of patients receiving thrombolysis in later treatment windows increased, and the there was an increase of the proportion of patients treated within 60 minutes of hospital admission. There were 16 symptomatic intracranial hemorrhage (7.7%), which was similar to the global cohort of the SITS registry (4.8%; P=0.09). In univariate analysis, symptomatic intracranial hemorrhage was associated with admission clinical severeness, prior use of statins, and onset-to-treatment. In multivariate analysis, clinical severeness and statin use were independently associated with symptomatic hemorrhage. CONCLUSIONS. Intravenous thrombolysis was safely performed in a brazilian, public, academic hospital, in spite of a severe clinical profile and a rather late treatment window. More efforts are necessary to improve stroke recognition, dispatch and delivery of acute stroke patients in Brazil, in order to decrease time to hospital arrival and to improve access to intravenous thrombolysis. Patients with more severe strokes and with prior use of statin therapy may have increased risk of symptomatic intracranial hemorrhage after thrombolysis for acute stroke

Improving mangrove above-ground biomass estimates using LiDAR

Tree height is a key parameter to accurately quantify above ground biomass (AGB) of trees. Approaches that integrate airborne light detection and ranging (LiDAR) with mapped extents of forests may improve estimation of mangrove heights by providing considerably more measurements of mangrove tree heights than can be achieved using field-based measurements alone. In this study, we present a validated method for quantifying mangrove AGB that was demonstrated for a mangrove forest at Guarás Island, Brazil. The application of LiDAR to estimate mangrove height was confirmed by correlating 89 tree heights measured in the field with LiDAR-derived mangrove heights, resulting in highly robust relationships for Avicennia germinans, Laguncularia racemosa and Rhizophora mangle (R2 = 0.90-0.97, RMSE of 1.24-0.67 m and RMSE% of 11.26%-25.97%). These relationships were used to calibrate a LiDAR-derived canopy height model (CHM) and develop robust relationships between the calibrated-CHM and field-based estimates of AGB (R2 = 0.85-0.92, RMSE of 3.1 kg-42.53 kg, RMSE% of 20.66%-43.81%). This relationship was then applied to the CHM whilst accounting for tree density to estimate mangrove AGB. Total mangrove AGB per hectare was estimated to be 246.90 t ha−1, corresponding closely with previous mangrove AGB measurements within the region. This study found that mangrove height and AGB are statistically related and these relationships can be applied to allometric equations for specific species to improve mangrove AGB estimates. This study demonstrates the capacity for LiDAR-derived tree heights to replace traditional approaches to estimating AGB and improving estimates of mangrove blue carbon storage. Application of LiDAR to determine tree heights will be particularly useful where mangrove is extensive and/or remote

Cat's claw oxindole alkaloid isomerization induced by common extraction methods

Cat's claw oxindole alkaloids are prone to isomerization in aqueous solution. However, studies on their behavior in extraction processes are scarce. This paper addressed the issue by considering five commonly used extraction processes. Unlike dynamic maceration (DM) and ultrasound-assisted extraction, substantial isomerization was induced by static maceration, turbo-extraction and reflux extraction. After heating under reflux in DM, the kinetic order of isomerization was established and equations were fitted successfully using a four-parameter Weibull model (R² > 0.999). Different isomerization rates and equilibrium constants were verified, revealing a possible matrix effect on alkaloid isomerization

Cats claw oxindole alkaloid isomerization induced by cell incubation and cytotoxic activity against T24 and RT4 human bladder cancer cell lines

The antitumor activity of Uncaria tomentosa, a native vine from the Amazonian rainforest, has been ascribed to pentacyclic oxindole alkaloids occurring in its bark. Former studies have shown that this activity, as well as its intensity, depends on whether catʼs claw alkaloids occur as original compounds or isomerized derivatives. This work addresses this aspect, using T24 and RT4 human bladder cancer cell lines for that purpose. Bark samples were extracted by dynamic maceration, prepurified with cross-linked polyvinylpyrrolidone and properly fractioned by an ion exchange process to obtain an oxindole alkaloid purified fraction. Alkaloid isomerization was induced by heating it under reflux at 85 °C. Samples collected after 5, 15, and 45 min of heating were analyzed by HPLC-PDA, freeze-dried at once, and separately assayed using the non-isomerized purified fraction for comparison purposes. The latter showed significant and dose-dependent cytotoxic activity against both T24 and RT4 cancer cell lines (IC50: 164.13 and 137.23 µg/mL, respectively). However, results for both cell lines were equivalent to those observed for isomerized samples (p > 0.05). The alkaloid isomerization induced by the incubation conditions (buffered medium pH 7.4 and temperature 37 °C) helps to explain the similar results obtained from non-isomerized and isomerized samples. Mitraphylline, speciophylline, uncarine F, and, to a lesser degree, pteropodine were more susceptible to isomerization under the incubation conditions. Thus, the alkaloid profile of all fractions and their cytotoxic activities against T24 and RT4 human bladder cancer cell lines are determined to a large extent by the incubation conditions

Radarsat-2 Backscattering for the Modeling of Biophysical Parameters of Regenerating Mangrove Forests

The aim of this study is to understand the relationship between radar backscattering (σ°, β° and γ) of a multi-polarized Radarsat-2 C-band image with the structural attributes of regenerating mangrove vegetation located at the mouth of the Amazon River. CBH (circumference at breast height), height and species data were collected to characterize vegetation structure and above-ground biomass (AGB) at 17 plots with a total of 3090 measured individuals. Significant relationships between the linear σ° in VH (vertical transmit, horizontal receive) cross-polarization produced r2 values of 0.63 for the average height, 0.53 for the DBH, 0.46 for the basal area (BA) and 0.52 for the AGB. Using co-polarized HH (horizontal transmit, horizontal receive) and VV (vertical transmit, vertical receive), r2 values increased to 0.81, 0.79, 0.67 and 0.79, respectively. Vegetation attribute maps of average canopy height, DBH and AGB were generated for the study area. We conclude that multi-polarized Radarsat-2 images were adequate for characterization of vegetation attributes in areas of mangrove regeneration