Hipertensão arterial sistêmica e dislipidemia: estudo de caso-controle

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clínica Médica

Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis

IntroductionEvidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.MethodsThirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.ResultsRNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.ConclusionThese findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients

Transcriptomic signatures of classical monocytes reveal pro-inflammatory modules and heterogeneity in polyarticular juvenile idiopathic arthritis

IntroductionPolyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity.MethodsA total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level.ResultsWe identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels.ConclusionThese findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine

Vertebral fractures, Incidence and risk factors for osteoporotic vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil

As fraturas vertebrais por osteoporose conferem risco aumentado de novas fraturas por fragilidade e maior mortalidade. Não há dados consistentes acerca da incidência de fratura vertebral osteoporótica em países de baixa/média renda, que têm experimentado aumento da expectativa de vida e envelhecimento populacional acelerado nas últimas décadas. Os objetivos deste estudo foram determinar a incidência de fratura vertebral osteoporótica, diagnosticada por radiografia, bem como identificar os principais fatores de risco para fratura em idosos brasileiros da comunidade, em um estudo coorte prospectivo de base populacional. Setecentos e sete indivíduos da comunidade, com 65 anos ou mais, foram avaliados através de radiografias da coluna vertebral obtidas no início do estudo e após um tempo médio de seguimento de 4,3 ± 0,8 anos. Nova fratura vertebral foi definida como uma alteração na morfologia vertebral resultando em maior grau de deformidade na segunda radiografia (graus 1-3), quando comparado com o exame inicial. Questionário (dados clínicos), medida da densidade mineral óssea (DMO) e exames laboratoriais foram realizados na avaliação inicial. Modelos de regressão multivariada de Poisson foram construídos para identificar os preditores independentes de fratura vertebral. Quatrocentos e quarenta e nove mulheres (72,9±4,8 anos) e 258 homens (72,3±4,7 anos) foram incluídos no estudo. A incidência de fratura vertebral ajustada para a idade foi 40,3/1000 pessoas-ano em mulheres e 30,6/1000 pessoas-ano em homens. Na análise multivariada três modelos possíveis de fatores de risco para fratura foram determinados em mulheres: 1. idade (RR 2,46, IC 95% 1,66-3,65, para cada aumento em 10 anos), fratura osteoporótica prévia (RR 1,65, IC 95% 1,00-2,71) e DMO da coluna lombar (RR 1,21, IC 95% 1,03-1,41, para cada redução de 1 DP na DMO); 2. idade (RR 2,25, IC 95% 1,52-3,34, para cada aumento em 10 anos) e DMO do colo do fêmur (RR 1,42, IC 95% 1,11-1,81, para cada redução de 1 DP na DMO); 3. Idade (RR 2,11, IC 95% 1,41-3,15, para cada aumento em 10 anos) e DMO do quadril total (RR 1,56, IC 95% 1,21-2,0, para cada redução de 1 DP na DMO). Em homens, o maior quartil de distribuição do telopeptídeo C-terminal (CTX) sérico (RR 1,96, IC 95% 0,98-3,91) e fratura prévia (RR 2,10, 95% CI 1,00-4,39) foram preditores de nova fratura vertebral, após ajustes para idade, peso e atividade física. Este é o primeiro estudo longitudinal que determinou a incidência de fratura vertebral em uma amostra de base populacional de idosos na América Latina. A frequência de fratura vertebral foi elevada nessa população. Idade, fratura prévia, DMO e marcadores bioquímicos da remodelação óssea foram preditores de nova fratura vertebralVertebral fractures are associated with increased future fracture risk and mortality. No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population\'s aging has been faster. Thus, we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. 707 older adults (449 women and 258 men) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 ± 0.8 years. New vertebral fracture was defined as distinct alteration in the morphology of vertebrae resulting in higher grade of deformity on the second radiograph when compared to the baseline radiograph. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. Multivariate Poisson regression models were used to identify independent predictors of fracture. The age-standardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men. In women, three models of risk factors for fracture were fitted: (1) age (relative risks (RR) 2.46, 95 % confidence interval (CI) 1.66-3.65), previous osteoporotic fracture (RR 1.65, 95 % CI 1.00-2.71), and lumbar spine BMD (RR 1.21, 95 % CI 1.03-1.41); (2) age (RR 2.25, 95 % CI 1.52-3.34) and femoral neck BMD (RR 1.42, 95 % CI 1.11-1.81); (3) age (RR 2.11, 95 % CI 1.41-3.15) and total hip BMD (RR 1.56, 95 % CI 1.21-2.0). In men, the highest quartile of cross-linked C-telopeptide (CTx) (RR 1.96, 95 % CI 0.98-3.91) and prior fracture (RR 2.10, 95 % CI 1.00-4.39) were predictors of new vertebral fracture. This is the first population-based study to ascertain the incidence of vertebral fracture in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, BMD, and bone turnover were predictors of the short-term incidence of vertebral fractur

Autoimmune hemolytic anemia in systemic lupus erythematosus: association with thrombocytopenia

Hematological disturbances are common in systemic lupus erythematous (SLE). Specifically, autoimmune hemolytic anemia (AHA) may manifest in SLE patients at the time of diagnosis or within the first year of the disease. AHA is often associated with thrombocytopenia, lupus nephritis, and central nervous system activity. In this study we investigated these associations in Brazilian patients with SLE. Forty-four consecutive SLE patients who had a history of AHA were age, gender, and disease duration matched with 318 SLE patients without AHA who formed the control group. All patients fulfilled the revised American College of Rheumatology criteria for SLE and were followed-up within our Service. Clinical and laboratorial manifestations were similar in both groups, except for the predominance of leukopenia, thrombocytopenia, and anti-dsDNA on univariate analysis in the AHA group. The multivariate logistic regression model revealed risk only for thrombocytopenia in the AHA group compared to the control group (odds ratio, 2.70; 95% confidence interval, 1.32-5.50). Our results corroborate previous data that AHA in SLE increases the risk of thrombocytopenia in individuals with SLE. This association suggests a common mechanism in AHA and SLE pathophysiologies

Características demográficas, clínicas, laboratoriais e radiológicas da febre reumática no Brasil: revisão sistemática Demographic, clinical, laboratorial, and radiological characteristics of rheumatic fever in Brazil: systematic review

A febre reumática (FR) se caracteriza por um processo inflamatório não supurativo que se instala após uma infecção pelo estreptococo beta-hemolítico do grupo A de Lancefield. Sua prevalência é maior nos países em desenvolvimento como o Brasil. Em nosso país, entretanto, dados epidemiológicos sistemáticos sobre a doença são incompletos e escassos. Estima-se uma prevalência de FR ao redor de 3% entre as crianças e os adolescentes brasileiros. Neste artigo, foi realizada uma revisão sistemática dos principais estudos brasileiros, utilizando como fonte de pesquisa as bases de dados do LILACS, Scielo e Medline, tendo como palavras-chave Febre Reumática e Rheumatic Fever. Foram selecionados 10 trabalhos epidemiológicos e a análise comparativa não demonstrou diferenças em relação a predominância de sexo, quadro clínico, laboratorial e radiológico dos pacientes nas diversas regiões do país.<br>Rheumatic fever (RF) is characterized by a non-suppurative inflammatory process that begins after a group A betahemolytic streptococci infection. Its prevalence is higher in developing countries, such as Brazil. However, in our country, systematic epidemiologic data on the disease are scarce and incomplete. Rheumatic fever has an estimated incidence of 3% among Brazilian children and adolescents. We undertook a systematic review of the main Brazilian studies using the LILACS, Scielo, and Medline databases searching for expressions like Febre Reumática and Rheumatic Fever. Ten epidemiological studies were selected and comparative analysis did not show a predominance of gender, clinical presentation, and laboratorial and radiological parameters in the different regions of the country