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Doctoral Thesis
DOI
https://doi.org/10.11606/T.22.2024.tde-25062024-101010
Document
Author
Full name
Francine Sanchez Gulin
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2024
Supervisor
Committee
Laus, Ana Maria (President)
Stabile, Angelita Maria
Gaspar, Gilberto Gambero
Martins, Maria Auxiliadora
Title in Portuguese
Avaliação dos critérios clínicos e utilização de biomarcadores na triagem da sepse fora da unidade de terapia intensiva
Keywords in Portuguese
Biomarcadores
Diagnóstico precoce
Enfermagem
Sepse
Abstract in Portuguese
A sepse, principal causa de morte por infecções, constitui um desafio significativo na saúde global. A busca por estratégias mais eficientes no diagnóstico e no manejo da sepse destaca a importância dos biomarcadores como ferramentas complementares aos métodos clínicos atuais. Este é um estudo de coorte prospectivo que teve como objetivo comparar os níveis plasmáticos de quimiocinas, citocinas pró e anti-inflamatórias, fatores de crescimento, metaloproteinases de matriz (MMPs) e os inibidores teciduais de metaloproteinases de matriz (TIMPs) de pacientes infectados versus não infectados; com qSOFA positivo versus qSOFA negativo e com SOFA positivo versus SOFA negativo fora da Unidade de Terapia Intensiva. Foi realizado nas enfermarias de clínica médica e cirúrgica de um hospital de ensino e grande porte do estado de São Paulo. Os pacientes elegíveis eram adultos, com 18 anos ou mais, de ambos os sexos, com internação mínima de 24 horas e com presença de infecção diagnosticada pelo médico. Pacientes em cuidados paliativos, com alterações neurológicas, escores qSOFA ou SOFA positivos na inclusão, diagnosticados com sepse ou em estado de choque na admissão foram excluídos do estudo. A coleta incluiu dados demográficos e clínicos e as pontuações dos escores SIRS, qSOFA e SOFA foram calculadas diariamente. As amostras de sangue, destinadas à quantificação dos biomarcadores, foram coletadas na inclusão do paciente e em cada ocorrência de escores qSOFA e SOFA positivos. Os escores clínicos qSOFA e SOFA foram avaliados até alcançarem pontuação positiva ou até o desfecho do paciente, fosse alta ou óbito. Formou-se um grupo controle com 30 indivíduos saudáveis. Nesse grupo, foram coletadas informações demográficas e amostras de sangue. Os mediadores imunológicos foram dosados utilizando ensaios Luminex® de múltiplos analitos. As análises estatísticas foram realizadas no software Graphpad Prisma, com intervalos de confiança de 95% e p-valor <0,05. Participaram 152 pacientes, a maioria do sexo masculino, média de idade de 52 anos. A maior prevalência de infecções foi em feridas cirúrgicas, afetando 34 (22,4%) pacientes. Dos 129 pacientes com, ao menos, um escore clínico positivo, dez (8%) tiveram qSOFA positivo e SOFA negativo, enquanto 23 (18%) apresentaram SOFA positivo e qSOFA negativo, evidenciando que, em 23 casos, o qSOFA não identificou a sepse. As dosagens dos marcadores imunológicos não foram realizadas em todos os participantes: 60 no grupo infectado na admissão, 27 com qSOFA positivo, 43 com SOFA positivo, dez no grupo controle, sete com qSOFA positivo/SOFA negativo e 23 com SOFA positivo/qSOFA negativo. As citocinas Eotaxina, FGF basic, IFNγ, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-12, IL-13, IL-15, IL-17, IP-10, MCP1, MIP-1a, MIP-1b, PDGF-bb, RANTES, TNF-α, além das MMP-9 e MMP-2, mostraram capacidade discriminatória e significância estatística na identificação de infecção. Citocinas como G-CSF, IFN-γ, IL-1ra, IL-5, IL-6, IL-8, IL-9, MIP-1a e MIP-1b foram eficazes em identificar, desde a admissão, pacientes que evoluíram para sepse (SOFA positivo) dos que não evoluíram. Nenhuma citocina detectou o momento em que o escore SOFA se tornou positivo. As MMP-9, MMP-2 e as TIMP1, -2, -3, -4 não se mostraram eficazes na identificação de sepse.
Title in English
Assessment of clinical criteria and use of biomarkers in sepsis screening outside the intensive care unit
Keywords in English
Biomarkers
Early diagnosis
Nursing
Sepsis
Abstract in English
Sepsis, the leading cause of death from infections, constitutes a significant global health challenge. The search for more efficient strategies in the diagnosis and management of sepsis highlights the importance of biomarkers as complementary tools to current clinical methods. This is a prospective cohort study that aimed to compare plasma levels of chemokines, pro- and anti-inflammatory cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs) in infected versus uninfected patients; with positive versus negative qSOFA and with positive versus negative SOFA outside the Intensive Care Unit. This study was carried out in the medical and surgical wards of a large educational hospital in the state of São Paulo. Eligible patients were adults, aged 18 or over, of both sexes, hospitalized for a minimum of 24 hours and with an infection diagnosed by a doctor. Patients in palliative care, with neurological changes, positive qSOFA or SOFA scores at inclusion, diagnosed with sepsis, or in a state of shock at admission were excluded from the study. Collection included demographic and clinical data and SIRS, qSOFA, and SOFA scores were calculated daily. Blood samples, intended for biomarker quantification, were collected at patient inclusion and at each occurrence of positive qSOFA and SOFA scores. The qSOFA and SOFA clinical scores were evaluated until they reached a positive score or until the patient's outcome, be it discharge or death. A control group was formed with 30 healthy individuals. Demographic information and blood samples were collected for this group. Immune mediators were measured using Luminex® multi-analyte assays. Statistical analyzes were performed using Graphpad Prisma software, with 95% confidence intervals and p-value <0.05. 152 patients participated, the majority of whom were male, with an average age of 52 years. The highest prevalence of infections was in surgical wounds, affecting 34 (22.4%) patients. Of the 129 patients with at least one positive clinical score, ten (8%) had positive qSOFA and negative SOFA, while 23 (18%) had positive SOFA and negative qSOFA, showing that in 23 cases, qSOFA did not identify sepsis. Measurements of immunological markers were not performed on all participants: 60 in the group infected upon admission, 27 with positive qSOFA, 43 with positive SOFA, ten in the control group, seven with positive qSOFA/negative SOFA, and 23 with positive SOFA/negative qSOFA. The cytokines Eotaxin, FGF basic, IFN-γ, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-12, IL-13, IL-15, IL-17, IP-10, MCP-1, MIP-1a, MIP-1b, PDGF-bb, RANTES, TNF-α, in addition to MMP-9 and MMP-2 showed discriminatory capacity and statistical significance in identifying infection. Cytokines such as G-CSF, IFN-γ, IL-1ra, IL-5, IL-6, IL8, IL-9, MIP-1a, and MIP-1b were effective in identifying, from admission, patients who progressed to sepsis (positive SOFA) of those who did not progress. No cytokine detected the moment at which the SOFA score became positive. MMP-9, MMP-2, and TIMP1, -2, - 3, -4 were not effective in identifying sepsis.
 
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Publishing Date
2024-07-05
 
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