Intravenous rtPA versus mechanical thrombectomy in acute ischemic stroke: A historical cohort in Joinville, Brazil.

Groundbreaking results concerning ischemic stroke (IS) hyperacute treatment worldwide were published in 2014 and 2015. We aimed to compare functional status after 3 months in patients treated with intra-arterial thrombectomy (IAT) and those treated with intravenous thrombolysis (IVT) alone in Joinville, Brazil. From the Joinville Stroke Registry, we extracted and compared all consecutive IVT patients treated with r-tPA within 4.5 h in the period 2009-2011 versus all consecutive IAT treated within 6 h with the Solitaire FR device plus IVT in the period 2012-2014. We registered 82 patients in the IVT group and 31 patients in the IAT group. At hospital admission, patients in the IAT group were significantly younger (p < 0.001), had a higher educational level (p = 0.001), had a slightly higher prevalence of atrial fibrillation (p = 0.057) and had more severe strokes measured by the NIH stroke scale (p = 0.011). After 90 days, 45% of patients in the IAT group and 27% in the IVT group were independent (0-1 points) according to the modified Rankin scale (adjusted odds ratio: 4.53; 95% CI: 1.22 to 16.75). Symptomatic hemorrhage was diagnosed in 10% of patients in both groups (p = 1.0). The 90-day case-fatality was 39% (32/82) in the IVT group and 26% (8/31) in the IAT group (p = 0.27). In this small cohort, a greater rate of functional independence was achieved in patients treated with IAT plus IVT, compared with patients treated with IVT lysis alone. Our "real-world" findings are consistent with results of controlled, randomized clinical trials.

Three-year survival and recurrence after first-ever stroke: the Joinville stroke registry.

BACKGROUND: Data estimating the recurrence and risk of death are lacking in low and middle income countries, where two thirds of the stroke burden occurs. Previously we had shown that the incidence and mortality have been decreasing over the last 18 years in Joinville, Southern Brazil. In this study, we aim to determine the recurrence rates, survival rates and the cause of death in 3 years after their first-ever incident in a urban population-based setting. METHODS: From the Joinville Stroke Registry, we identified all the cases of first-ever stroke that occurred from October 2009 to September 2010. Multiple overlapping sources of information were used to ensure the completeness of case identification. Patients were followed up prospectively at regular intervals from 30-days to 3 years after the index event. Kaplan-Meir and Cox proportional hazards were used to assess the cumulative risk of death and recurrence. RESULTS: We registered 407 first-ever stroke patients. After 3 years, 136 (33%) had died. In the first year of stroke the risk of death was 28% (95% CI, 25 to 32). Beyond the first year, approximately 3 to 5% of survivors died each year. The cumulative risk of death in ischemic stroke (IS) subtypes was 3.6 higher for cardioembolic (CE) IS (hazard ratio 3.6, 95% CI, 2.1 to 6.4; p = 0.001) and 3.3 times higher for undetermined IS (HR 3.3, 95% CI 1.9 to 5.8; p = 0.001) compared to small artery occlusion IS. Over 3 years, the overall stroke recurrence risk was 9% (35/407). We found no difference in stroke recurrence risk between IS subtypes. Cardiovascular disease was the main cause of death all follow up time. CONCLUSIONS: Compared to other cohort studies conducted between 10 and 20 years ago in high-income countries, our recurrence rates and 3-year risk of death were similar. Among IS subtypes, we confirmed that CE has highest risk of death. The most common cause of death after a first-ever stroke is cardiovascular disease. This has implications for the uptake of current secondary preventive strategies and the development of new strategies.

Trends of the Incidence of Ischemic Stroke Thrombolysis over Seven Years and One-Year Outcome: A Population-Based Study in Joinville, Brazil.

BACKGROUND: In a population-based setting, we aimed to measure the incidence trends of ischemic stroke (IS) thrombolysis, thrombolysis times, proportion of symptomatic intracerebral hemorrhage (sICH), 30-day case fatality and functional outcomes. We also compared the 12-month functional status between thrombolyzed and nonthrombolyzed patients. METHODS: Using data from the Joinville Population-Based Stroke Registry, we prospectively ascertained a cohort of all thrombolyses done in Joinville citizens, Southern Brazil, from 2005 to 2011. For the definition of sICH we used European Cooperative Acute Stroke Study (ECASS) II criteria. RESULTS: Over 7 years, 6% (220/3,552) of all IS were thrombolyzed. The thrombolysis incidence increased from 1.4 [95% confidence interval (CI), 0.6-2.9] in 2005 to 9.8 (7.3-12.9) per 100,000 population in 2011 (p < 0.0001). The thrombolysis incidence age-adjusted to the world population in 2011 was 11 (8.2-14.3) per 100,000. Only 30% (50/165) were thrombolyzed within 1 h of arrival at hospital. In 7 days, 6.4% (14/220) had sICH and 57% (8/14) of those died. In the 2009-2011 period, a favorable functional outcome [modified Rankin scale (mRS) 0-1] at 12 months among patients who received thrombolysis was more frequent [mRS 0-1; 36% (38/107)] than among patients who did not receive thrombolysis [mRS 0-1; 24% (131/544); p = 0.016]. The logistic regression showed that thrombolyzed IS patients had a more favorable outcome (mRS 0-1; HR 2.13; 95% CI, 1.2-3.7; p < 0.016) than nonthrombolyzed patients. CONCLUSION: In a population setting of a middle income country, the thrombolysis incidence and outcomes were similar to those of other well-structured services. After 1 year, patients thrombolyzed in the 4.5-hour time window had a better outcome. More than proportions, rates provide additional information and could be used to benchmark services against others.

Functional characterization of the sciarid BhC4-1 core promoter in transgenic Drosophila.

BACKGROUND: Core promoters are cis-regulatory modules to which bind the basal transcriptional machinery and which participate in the regulation of transcription initiation. Although core promoters have not been extensively investigated through functional assays in a chromosomal context, the available data suggested that the response of a given core promoter might vary depending on the promoter context. Previous studies suggest that a (-57/+40) fragment constitutes the core promoter of the BhC4-1 gene which is located in DNA puff C4 of the sciarid fly Bradysia hygida. Here we tested this (-57/+40) fragment in distinct regulatory contexts in order to verify if promoter context affects its core promoter activity. RESULTS: Consistent with the activity of a core promoter, we showed that in the absence of upstream regulatory sequences the (-57/+40) fragment drives low levels of reporter gene mRNA expression throughout development in transgenic Drosophila. By assaying the (-57/+40) fragment in two distinct regulatory contexts, either downstream of the previously characterized Fbp1 enhancer or downstream of the UAS element, we showed that the BhC4-1 core promoter drives regulated transcription in both the germline and in various tissues throughout development. Furthermore, the use of the BhC4-1 core promoter in a UAS construct significantly reduced salivary gland ectopic expression in third instar larvae, which was previously described to occur in the context of the GAL4/UAS system. CONCLUSIONS: Our results from functional analysis in transgenic Drosophila show that the BhC4-1 core promoter drives gene expression regardless of the promoter context that was assayed. New insights into the functioning of the GAL4/UAS system in Drosophila were obtained, indicating that the presence of the SV40 sequence in the 3' UTR of a UAS construct does not preclude expression in the germline. Furthermore, our analysis indicated that ectopic salivary gland expression in the GAL4/UAS system does not depend only on sequences present in the GAL4 construct, but can also be affected by the core promoter sequences in the UAS construct. In this context, we propose that the sciarid BhC4-1 core promoter constitutes a valuable core promoter which can be employed in functional assays in insects.