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Maria do Carmo Pereira Nuneshttp://lattes.cnpq.br/7052421532116243Teresa Cristina de Abreu Ferrarihttp://lattes.cnpq.br/8298538465228015http://lattes.cnpq.br/4385604002428419Milton Henriques Guimarães Júnior2022-03-31T12:28:34Z2022-03-31T12:28:34Z2017-08-11http://hdl.handle.net/1843/40655INTRODUÇÃO: Endocardite infecciosa (EI) é uma doença grave com elevadas taxas de morbidade e mortalidade. Os fatores preditores de evolução da EI são determinados por complexos processos, como interação patógeno-hospedeiro, estabelecimento de um padrão da resposta imune e inflamatória, assim como ativação celular. Recentemente, crescente número de trabalhos científicos demonstraram a participação das micropartículas derivadas de células (MPs) nesses processos. Entretanto, não existem estudos que avaliaram as MPs na EI, tanto ao diagnóstico quanto durante o tratamento, e sua relação com desfechos clínicos. O presente estudo foi desenhado para avaliar os níveis séricos das MPs derivadas de leucócitos, neutrófilos, monócitos, linfócitos T, células endoteliais, eritrócitos e plaquetas em pacientes com EI. O perfil das MPs foi analisado durante o tratamento para se determinar o impacto desses novos marcadores nos desfechos clínicos, definidos como necessidade de cirurgia precoce e morte intrahospitalar, desenvolvimento de insuficiência cardíaca e acidente vascular cerebral (AVC). Além disso, a concentração das MPs na EI foi comparada com outras infecções bacterianas. MÉTODOS: Entre agosto 2011 e janeiro 2017, 57 pacientes com EI provável ou definitiva, segundo os critérios de Duke modificados, internados no Hospital das Clínicas da UFMG foram incluídos. Os pacientes foram acompanhados durante a internação com coleta dos dados clínicos, laboratoriais e ecocardiográficos. Amostras plasmáticas foram obtidas em três tempos: à admissão hospitalar (T0), após duas semanas de tratamento (T1) e ao final do tratamento (T2). Os pacientes com EI foram comparados a um grupo controle composto por 22 pacientes com outras infecções bacterianas, caracterizadas por febre e elevação da proteína C reativa (PCR). MPs foram dosadas pela citometria de fluxo, utilizando-se a anexina como um marcador universal e anticorpos marcados direcionados a antígenos celulares específicos CD45 (leucócitos), CD66b (neutrófilos), CD14 (monócitos), CD41a (plaquetas), CD51 (células endoteliais) e CD235a (eritrócitos). Os pacientes foram tratados conforme recomendações dos guidelines e a indicação cirúrgica foi baseada em critérios bem estabelecidos pela literatura. RESULTADOS: A mediana da idade dos pacientes foi de 50 anos, com 33 pacientes do sexo masculino (58%). A condição predisponente mais frequente foi cardiopatia reumática, detectada em 30% dos casos. Os microrganismos mais prevalentes foram staphylococcus (37%), seguido dos streptococcus (12%). Em 17 pacientes (30%), a hemocultura foi negativa. MPs de plaquetas (pltMPs), leucócitos (leucMPs), neutrófilos (neutMPs) e linfócitos T (linfMPs) foram significativamente elevadas nos pacientes com EI , em comparação aos pacientes com outras infecções bacterianas, apesar de idade, sexo, global de leucócitos e proteína C reativa comparáveis. Avaliando-se o comportamento das MPs com o tratamento, observou-se que os valores de MPs apresentaram um padrão relativamente estável ao longo do tempo, com exceção de um aumento significativo de leucMPS e neutMPs entre T0 e T1. Durante internação hospitalar, 17 pacientes evoluíram para o óbito (30%), 25 necessitam cirurgia cardíaca (44%), 29 desenvolveram insuficiência cardíaca (51%) e 9 tiveram AVC (16%). Em relação aos desfechos, leucMPs, neutMPs, linfMPs e MPs de monócitos (monoMPs), medidas à admissão, foram significativamente elevados nos pacientes com EI que morreram durante a hospitalização, em comparação aos pacientes sobreviventes. Não houve diferença nos níveis das MPs, comparando-se os pacientes que necessitaram de cirurgia cardíaca com o tratamento clínico, ou entre aqueles que desenvolveram insuficiência cardíaca ou não, e aqueles que tiveram ou não AVC. Em uma análise multivariada, os níveis de neutMPs permaneceram como um fator independente associado à mortalidade (OR 2,2 para cada aumento de 100 contagens/µL, intervalo de confiança de 95% de 1,2 a 4; p=0,009) CONCLUSÕES: As concentrações plasmáticas das MPs de leucócitos, neutrófilos, linfócitos T e plaquetas foram significativamente elevadas nos pacientes com EI, quando comparados a outras infecções bacterianas. Exceto pela elevação significativa das MPs derivadas dos neutrófilos, os níveis das MPs apresentaram um padrão relativamente estável ao longo dos três tempos avaliados. MPs derivadas dos leucócitos, incluindo neutrófilos, monócitos, e linfócitos, estavam elevadas nos pacientes que faleceram durante a internação. As MPs apresentam um valor potencial na EI, auxiliando no diagnóstico diferencial com outras infecções bacterianas e útil na identificação dos pacientes com maior risco de óbito.INTRODUCTION: Infectious endocarditis (IE) is a serious disease, with high rates of morbidity and mortality. IE evolution are determined by complex processes, such as pathogen-host interaction, establishment of a pattern of immune and inflammatory response, as well as cellular activation. Recently, a growing number of scientific studies have demonstrated the participation of cell-derived microparticles (MPs) in these processes. However, to date, there are no studies evaluating MPs in IE, both at diagnosis and during treatment, and its relation to clinical outcomes. The present study was designed to evaluate the serum levels of MPs derived from leukocytes, neutrophils, monocytes, T lymphocytes, endothelial cells, erythrocytes and platelets in patients with IE. The profile of MPs was analyzed during treatment to determine the impact of these new markers on clinical outcomes, defined as the need for early surgery and in-hospital death, the development of heart failure and stroke. In addition, the concentration of MPs in IE was compared with other bacterial infections. METHODS: Between August 2011 and January 2017, 57 patients with probable or definite IE according to the modified Duke criteria hospitalized at the Hospital das Clínicas of UFMG were included. The patients were followed up during the hospitalization with clinical, laboratory and echocardiographic data collection. Plasma samples were obtained at three times: at hospital admission (T0), after two weeks of treatment (T1) and at the end of treatment (T2). Patients with IE were compared to a control group composed of 22 patients with other bacterial infections, characterized by fever and elevated C-reactive protein (CRP). MPs were measured by flow cytometry, using annexin as a universal marker and labeled antibodies directed to specific cell antigens: CD45 (leukocytes), CD66b (neutrophils), CD14 (monocytes), CD41a (platelets), CD51 (endothelial cells) and CD235a (erythrocytes). The patients were treated according to the recommendations of the guidelines and the surgical indication was based on criteria well established in the literature. RESULTS: The median age of the patients was 50 years, with 33 male patients (58%). The most frequent predisposing condition was rheumatic heart disease, detected in 30% of the cases. The most prevalent microorganisms were staphylococcus (37%), followed by streptococcus (12%). In 17 patients (30%), blood culture was negative. Platelet MPs (pltMPs), leukocytes (leukMPs), neutrophils (neutMPs), and T lymphocytes (lympMPs) were significantly elevated in patients with IE compared to patients with other bacterial infections despite age, sex, global leukocyte and protein C reactive. By evaluating the MPs kinetics during the treatment, we observed that the MPs values had a relatively stable pattern over time, except for a significant increase of leukMPS and neutMPs between T0 and T1. During hospital stay, 17 patients died (30%), 25 needed heart surgery (44%), 29 had heart failure (51%) and 9 had a stroke (16%). Regarding the outcomes, leukMPs, neutMPs, lymphMPs and MPs of monocytes (monoMPs), measured at admission, were significantly elevated in patients with IE who died during hospitalization compared to patients who survived. There was no difference in MP levels, comparing patients who required cardiac surgery with the ones on clinical treatment, or those who developed heart failure or not, or that complicated or not with stroke. In a multivariate analysis, neutMPs levels remained an independent factor associated with mortality (OR 2.2 for each increase of 100 counts/μL, 95% confidence interval 1.2 to 4, p = 0.009) CONCLUSIONS: Plasma concentrations of MPs of leukocytes, neutrophils, T lymphocytes and platelets were significantly elevated in patients with IE when compared to other bacterial infections. Except for the significant elevation of MPs derived from neutrophils, MP levels presented a relatively stable pattern throughout the three evaluated times. MPs derived from leukocytes, including neutrophils, monocytes, and lymphocytes, were elevated in patients who died during hospitalization. The MPs present a potential value in IE, aiding in the differential diagnosis with other bacterial infections and useful in the identification of patients with higher risk of death.porUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências da Saúde - Infectologia e Medicina TropicalUFMGBrasilMEDICINA - FACULDADE DE MEDICINAEndocarditeMicropartículas Derivadas de CélulasVesículas ExtracelularesBiomarcadoresEndocardite InfecciosaMicropartículas derivadas de célulasVesículas extracelularesMarcadores inflamatóriosEstudo das micropartículas derivadas de células na endocardite infecciosa.Study of cell-derived microparticles in infective endocarditisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALEstudo das micropartículas derivadas de células na endocardite infecciosa (MARÇO 2022).pdfEstudo das micropartículas derivadas de células na endocardite infecciosa (MARÇO 2022).pdfapplication/pdf1277040https://repositorio.ufmg.br/bitstream/1843/40655/10/Estudo%20das%20micropart%c3%adculas%20derivadas%20de%20c%c3%a9lulas%20na%20endocardite%20infecciosa%20%28MAR%c3%87O%202022%29.pdfa548353abec18c96b2caec5328ec8d34MD510LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/40655/11/license.txtcda590c95a0b51b4d15f60c9642ca272MD5111843/406552022-03-31 09:28:34.572oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-03-31T12:28:34Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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