The influence of a TNF gene polymorphism on the severity of rheumatoid arthritis in the Brazilian Amazon.

PURPOSE: The aim of this study was to investigate the influence of the TNF -308 G/A polymorphism in the promoter region of the tumor necrosis factor-α gene on the susceptibility and severity of rheumatoid arthritis (RA) in individuals from the Brazilian Amazon. METHODS: A total of 323 individuals-192 healthy controls without arthritis and 131 individuals suffering from arthritis-were genotyped for this polymorphism using a methodology based on PCR-RFLP. RESULTS: The frequency of the A allele (TNF2) in rheumatoid arthritis sufferers was not significantly higher than in the controls (p=0.926; OR=0.97; confidence interval 0.54-1.76). However, using a logistic regression model, when the patients were stratified according to whether the manifestations were preponderantly articular or systemic, there was a strong association between the TNF2 allele and systemic arthritis (p=0.001; OR=5.89; confidence interval=1.98-17.5) as well as the use of anti-TNF immunotherapy (p=0.023; OR=1.10; confidence interval=1.00-1.14). The main factors that were found to influence the risk of extra-articular disease were age greater than or equal to 60 years (p=0.008; OR=4.06; confidence interval=1.45-11.38), disease duration greater than 10 years (p=0.031; OR=3.10; confidence interval=1.11-8.63) and positive rheumatoid factor (p=0.035; OR=2.07; confidence interval=1.05-4.09). CONCLUSIONS: These results suggest that the TNF2 allele is associated with the more serious forms of the disease in individuals from the Brazilian Amazon but not with a risk for developing RA.

Interaction between smoking and HLA-DRB1*04 gene is associated with a high cardiovascular risk in Brazilian Amazon patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints that affects approximately 1% of the population worldwide. The HLA-DRB1 gene locus plays a major role in genetic susceptibility to RA, a condition that has been associated with a high cardiovascular morbidity and mortality in many studies. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to investigate which types of HLA class II genes are associated with RA in patients from the Brazilian Amazon and their influence on high cardiovascular risk status in this population. For this purpose, a case-control study was carried out with a total of 350 non-Indian individuals made up of a cohort of 132 consecutive RA sufferers and 218 healthy controls. A χ(2) test showed that HLADRB1*04 (p<0.0016; OR = 1.89; 95% CI = 1.29-2.79) and HLADRB1*10 (p = 0.0377; OR = 3.81; 95% CI = 1.16-12.50) are the major HLA genes associated with susceptibility to RA. A logistic regression model also showed that the interaction between HLADRB1*04 (p = 0.027; OR = 6.02; 95% CI = 1.21-29.7), age (p = 0.0001; OR = 1.26; 95% CI = 1.13-1.39) and smoking (p = 0.0001; OR = 23.6; 95% CI = 4.25-32.1) is associated with a probability of a high cardiovascular risk status at an early age. CONCLUSIONS/SIGNIFICANCE: The results of this study show for the first time that HLA class II type is associated with RA in Brazilian Amazon populations and that a specific interaction between the HLA-DRB1*04 gene and smoking is associated with a high cardiovascular risk status, as initially reported in the European population. This study therefore contributes to an understanding of gene-environment interactions in RA patients.

Sepse: diagnóstico e tratamento / Sepsis: diagnosis and treatment

JUSTIFICATIVA E OBJETIVOS: A sepse é um importante problema de saúde no Brasil, incluindo serviços públicos e privados, com altos custos de tratamento e mortalidade. Desde 2003, a Campanha Sobrevivendo a Sepse vem sugerindo a implementação de medidas para o tratamento desta condição mórbida, de modo a reduzir sua mortalidade em 25%. O objetivo deste estudo foi contextualizar a atividade do emergencista no tratamento da sepse, bem como revisar os principais aspectos da epidemiologia da sepse no Brasil e seus tratamentos com base na Campanha Sobrevivendo a Sepse. CONTEÚDO: Utilizando as palavras-chave sepse, Surviving Sepsis Campaign, epidemiologia, fisiopatologia foi procedida a busca de referências no PubMed, Scopus, SciElo. Na Campanha Sobrevivendo à Sepse, foi utilizado um sistema de notas para orientar a avaliação de qualidade e evidência de alta (A) a muito baixa (D) e, deste modo, determinar a força de recomendações. Neste artigo foram registradas estas recomendações como: recomendação forte [1] indica os efeitos desejáveis da intervenção claramente superiores aos seus efeitos indesejáveis, ou claramente não; recomendação fraca [2] indica que a distinção entre os efeitos desejáveis e indesejáveis é menos clara. CONCLUSÃO: O clinico e, sobretudo o clínico emergencista, exerce papel central no tratamento da sepse na medida em que novas evidencias demonstram que a precocidade do tratamento é peça-chave no sucesso do tratamento.

BACKGROUND AND OBJECTIVES: Sepsis remains an important international health problem including Brazil, with high treatment costs and unacceptable morbidity and mortality. Since 2003, the Sepsis Surviving Campaign was created and suggested guidelines for sepsis and the campaign objective is reducing sepsis mortality rate around 25%. In this aim this work reviews the most important aspects of sepsis diagnosis and treatment, especially in the emergencist physician context and abording Brazilian epidemiology aspects. CONTENTS: This overview was performed using sepsis, septic shock, Surviving Sepsis Campaign, sepsis epidemiology and fisiopathology as keywords in PubMed, Scopus and Scielo databases. In Surviving Sepsis Campaign, was used a grade system to guide assessment to quality and evidence from high (A) to very low (D) and, at this way, determine the strength of recommendations. In this article this recommendations was registered as a follow: strong recommendation [1] indicates the intervention?s desirable effects clearly outweigh its undesirable effects, or clearly do not; weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. CONCLUSION: Physicians, even emergence physicians, plays a central role in the modern management of sepsis and septic shock, across the golden hours of treatment, which ones new evidences demonstrate the importance of nearly approach of patient's results in sepsis mortality decrease