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PURPOSE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found. CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.

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The efficiency of the immune system has been shaped throughout the evolutionary process allowing adaptations. In a Plasmodium vivax infection, the host attempts to develop an innate immune response to keep in check the parasite that is associated with inflammatory and regulatory processes. Production of pro-inflammatory and regulatory cytokines simultaneously appears to be a balancing mechanism for the host to prevent the onset of severe disease. Changes in the dynamics of circulating cytokines production can influence the pathogenesis, severity of the disease and episodes of recurrent Plasmodium vivax malaria (Pv-malaria). A cross-sectional study was conducted in endemic areas for Pv-malaria in the Amazonas State, Brazil. Several SNPs in TLR genes were genotyped by PCR-RFLP in 137 patients infected with P. vivax. Circulating cytokines IL-6, TNF, IL-2, IL-10, IFN-γ and IL-4 were measured by CBA. Influence of the studied SNPs on circulating cytokines was investigated by applying the Kruskal-Wallis test followed by Dunns' multiple comparison post-test. A Spearman correlation test also was performed to elaborate circulating cytokine networks and to demonstrate the level of interaction between each molecule. Individuals with genotypes A/G (TLR4 A299G), C/C (TLR6 S249P) and T/T (TLR9 -1486C/T) appear to produce less/gain IL-6, IFN-γ, IL-10, IL-2 and IL-4 compared to patients with wild-type and heterozygous genotypes. In addition, these genotypes seem to influence the interaction network between the molecules studied, causing a lower interaction, absence or even negative interaction between the cytokines. Data presented in this study suggests the influence of polymorphisms TLR4 (A299G), TLR6 (S249P) and TLR9 (-1486C/T) on the production of circulating cytokines during Pv-malaria.

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INTRODUCTION: Dengue is one of the most prevalent infectious diseases in Brazil and is a major public health problem worldwide. It is most prevalent in tropical and subtropical regions with 2.5 to 3 billion people at risk of becoming infected. Thus, this study sought to demonstrate the epidemiological characteristics of individuals affected by dengue, its prevalence and its epidemic process in the Middle Solimões region of Coari in the state of Amazonas between 2008 and 2009. METHODS: Epidemiological data were obtained through epidemiological monitoring by the Municipal Health Facility of the city of Coari, AM. The variables analyzed were the month of notification, the number of confirmed cases, the cases' genders, the cases' ages and their neighborhoods of residence. RESULTS: In total, 1,003 cases were reported (635 in 2008 and 368 in 2009), and 639 cases were diagnosed as positive. Of these, +54% involved female subjects, and +46% were male. The majority of the affected individuals were between 10 and 49 years of age, and the spatial distribution was concentrated in neighborhoods near streams, lakes and areas in which housing had recently been disrupted. CONCLUSIONS: We concluded that, during the period studied, there was an outbreak of dengue in the City of Coari, AM. However, it is possible that a dengue epidemic may have occurred earlier in Coari without proper diagnosis or follow-up and that previously infected individuals may have traveled to the capital of Amazonas (Manaus), where the virus has circulated since 1998.

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INTRODUÇÃO: A dengue é uma das doenças infecciosas mais frequentes no Brasil e um dos principais problemas de saúde pública no mundo, principalmente em regiões tropicais e subtropicais, com 2,5 a 3 bilhões de pessoas expostas ao risco de serem infectadas atualmente. Deste modo, o presente estudo teve como objetivo demonstrar as características epidemiológicas dos indivíduos acometidos por dengue, sua prevalência e seu processo epidêmico na região do Médio Solimões, Coari, Amazonas, no período de 2008 e 2009. MÉTODOS: Os dados epidemiológicos foram obtidos na Vigilância Epidemiológica da Secretaria Municipal de Saúde da Cidade de Coari-AM. As variáveis analisadas foram: mês da notificação, casos confirmados, gênero (sexo), faixa etária e bairro de residência. RESULTADOS: No total, foram notificados 1.003 casos (635 em 2008 e 368 em 2009), sendo diagnosticados 639 casos positivos. Destes, ± 54% acometerem indivíduos do sexo feminino e ± 46% do sexo masculino. As faixas etárias mais acometidas foram às observadas entre 10-49 anos; quanto à distribuição espacial, observamos o acometimento de indivíduos de bairros próximos a igarapés, lagos e com processo recente e desordenado de habitação. CONCLUSÕES: Deste modo, conclui-se que, durante o período estudado, houve um surto epidêmico de dengue na Cidade de Coari, AM. Entretanto, deve-se considerar que uma epidemia de dengue anterior pode ter ocorrido em Coari, sem que tenha tido o devido diagnóstico etiológico, ou que houveram pessoas com infecção passada que se deslocaram para a capital do Amazonas (Manaus), onde os vírus circulam desde 1998.

INTRODUCTION: Dengue is one of the most prevalent infectious diseases in Brazil and is a major public health problem worldwide. It is most prevalent in tropical and subtropical regions with 2.5 to 3 billion people at risk of becoming infected. Thus, this study sought to demonstrate the epidemiological characteristics of individuals affected by dengue, its prevalence and its epidemic process in the Middle Solimões region of Coari in the state of Amazonas between 2008 and 2009. METHODS: Epidemiological data were obtained through epidemiological monitoring by the Municipal Health Facility of the city of Coari, AM. The variables analyzed were the month of notification, the number of confirmed cases, the cases' genders, the cases' ages and their neighborhoods of residence. RESULTS: In total, 1,003 cases were reported (635 in 2008 and 368 in 2009), and 639 cases were diagnosed as positive. Of these, +54% involved female subjects, and +46% were male. The majority of the affected individuals were between 10 and 49 years of age, and the spatial distribution was concentrated in neighborhoods near streams, lakes and areas in which housing had recently been disrupted. Conclusions: We concluded that, during the period studied, there was an outbreak of dengue in the City of Coari, AM. However, it is possible that a dengue epidemic may have occurred earlier in Coari without proper diagnosis or follow-up and that previously infected individuals may have traveled to the capital of Amazonas (Manaus), where the virus has circulated since 1998.

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