Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study.

OBJECTIVE: To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit. METHODS: A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aß (1-42)], Aß (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge. RESULTS: Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder. CONCLUSION: Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-ß levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE.

Stratification to predict the response to antioxidant. / Estratificação para predizer a resposta ao tratamento antioxidante em terapia intensiva: um estudo translacional.

OBJECTIVE: To examine the effectiveness of stratification to identify and target antioxidant therapy for animal models of lethal sepsis and in patients who develop sustained hypotension. METHODS: Rats were subjected to sepsis induced by cecal ligation and puncture. Animals were divided into two groups: those with high and low plasma levels of interleukin-6. Following stratification, N-acetylcysteine plus deferoxamine or saline was administered to animals starting 3 and 12 hours after surgery. N-Acetylcysteine plus deferoxamine or placebo was administered within 12 hours of meeting the inclusion criteria in hypotensive patients. RESULTS: N-Acetylcysteine plus deferoxamine increased survival in the cecal ligation and puncture model when administered 3 and 12 hours after sepsis induction. When dividing animals that received antioxidants using plasma interleukin-6 levels, the protective effect was observed only in those animals with high IL-6 levels. The antioxidant effect of N-acetylcysteine + deferoxamine was similar in the two groups, but a significant decrease in plasma interleukin-6 levels was observed in the high-interleukin-6-level group. Compared with patients treated with antioxidants in the low-interleukin-6 subgroup, those in the high-interleukin-6 subgroup had a lower incidence of acute kidney injury but were not different in terms of acute kidney injury severity or intensive care unit mortality. CONCLUSION: Targeting antioxidant therapy to a high inflammatory phenotype would select a responsive population.

Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study / Biomarcadores de disfunção neuropsiquiátrica em sobreviventes de unidades de terapia intensiva: um estudo de coorte prospectivo

ABSTRACT Objective: To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit. Methods: A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aβ (1-42)], Aβ (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge. Results: Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder. Conclusion: Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

RESUMO Objetivo: Avaliar os fatores associados aos desfechos neuropsiquiátricos de longo prazo, incluindo biomarcadores, medidos após a alta da unidade de terapia intensiva. Métodos: Foi realizado um estudo de coorte prospectivo com 65 sobreviventes de unidades de terapia intensiva. A avaliação cognitiva foi realizada por meio do Miniexame do Estado Mental; os sintomas de ansiedade e depressão foram avaliados por meio da Escala Hospitalar de Ansiedade e Depressão, e o transtorno de estresse pós-traumático foi avaliado pela Escala de Impacto do Evento-6. Os níveis plasmáticos de beta amiloide (1-42), beta amiloide (1-40), interleucina 10, interleucina 6, interleucina 33, interleucina 4, interleucina 5, fator de necrose tumoral alfa, proteína C-reativa e fator neurotrófico derivado do cérebro foram medidos na alta da unidade de terapia intensiva. Resultados: Das variáveis associadas à terapia intensiva, apenas o delirium foi relacionado de forma independente à ocorrência de comprometimento cognitivo de longo prazo. Além disso, níveis mais altos de interleucina 10 e interleucina 6 foram associados à disfunção cognitiva. Apenas a interleucina 6 foi associada de forma independente à depressão. A ventilação mecânica, os níveis de interleucina 33 e os níveis de proteína C-reativa foram associados de forma independente à ansiedade. Nenhuma variável foi associada de forma independente ao transtorno de estresse pós-traumático. Conclusão: A disfunção cognitiva, bem como os sintomas de depressão, ansiedade e transtorno de estresse pós-traumático, estão presentes em pacientes que sobrevivem a uma doença grave, e alguns desses desfechos estão associados aos níveis de biomarcadores inflamatórios medidos na alta da unidade de terapia intensiva.

Perfil dos usuários e atendimento das Unidades Básicas de Saúde do município de Criciúma (SC) / Profile of users and services of Basic Health Units in the municipality of Criciúma (SC) / Perfil de usuarios y atención de unidades básicas de salud en el municipio de Criciúma (SC)

O objetivo deste estudo foi avaliar as características dos usuários e dos atendimentos realizados nas Unidades Básicas de Saúde do município de Criciúma/SC. Foram avaliados todos atendimentos realizados no ano de 2018, através da coleta de dados secundários no sistema de informação em saúde (CELK Saúde) do município. As variáveis analisadas foram: idade, sexo, escolaridade, situação de moradia, encaminhamentos realizados à atenção secundária, classificação e tipos de atendimentos registrados durante as consultas e os principais procedimentos executados. Foram realizadas análises descritivas das variáveis estudadas, com a apresentação das frequências absolutas e relativas. Dentre os 452.605 atendimentos avaliados, observou-se que 64,57% dos atendimentos foram realizados pelo sexo feminino e pelos indivíduos com 60 anos ou mais. A maior prevalência de atendimentos foi na classificação saúde mental. Em relação aos tipos de atendimento, notou-se predominância de consulta médica em todos os distritos. Quanto aos encaminhados realizados à atenção secundária, os mais prevalentes foram a oftalmologia e a ortopedia. Os resultados encontrados neste estudo podem orientar os gestores em saúde no desenvolvimento de estratégias e alternativas de intervenções efetivas na atenção básica, melhorando a qualidade e otimizando os serviços públicos ofertados.

The aim of this study was to evaluate the characteristics of users and services provided at Basic Health Units in the municipality of Criciúma/SC. All consultations performed in 2018 were evaluated, through the collection of secondary data in the health information system (CELK Saúde) of the municipality. The following variables were analyzed: age, sex, education, housing situation, referrals to secondary care, classification and types of care recorded during consultations and the main procedures performed. Among the 452,605 consultations evaluated, it was observed that 64.57% of the visits were made by females and by individuals aged 60 or older. The highest prevalence of appointments was in mental health classification. Regarding the types of care, there was a predominance of medical appointments in all districts. As for those referred to secondary care, the most prevalent were ophthalmology and orthopedics. The results found in this study can guide health managers in the municipality, in developing strategies and alternatives for effective interventions in primary care, improving quality and optimizing the public services offered.

El objetivo de este estudio fue evaluar las características de los usuarios y la atención realizada en las Unidades Básicas de Salud del municipio de Criciúma/SC. Toda la atención brindada en 2018 fue evaluada a través de la recolección de datos secundarios en el sistema de información de salud (CELK Saúde) del municipio. Las variables analizadas fueron: edad, sexo, escolaridad, situación habitacional, derivaciones a atención secundaria, clasificación y tipos de atención registrados durante las consultas y los principales procedimientos realizados. Se realizaron análisis descriptivos de las variables estudiadas, con la presentación de frecuencias absolutas y relativas. Entre las 452.605 visitas evaluadas, se observó que el 64,57% de las visitas fueron realizadas por mujeres e individuos de 60 años o más. La mayor prevalencia de atención fue en la clasificación de salud mental. En cuanto a los tipos de atención, hubo un predominio de la consulta médica en todos los distritos. En cuanto a los referidos a cuidados secundarios, los más prevalentes fueron oftalmología y ortopedia. Los resultados encontrados en este estudio pueden orientar a los gestores sanitarios en el desarrollo de estrategias y alternativas para intervenciones eficaces en atención primaria, mejorando la calidad y optimizando los servicios públicos ofrecidos.

Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis.

BACKGROUND: The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. METHODS: Sepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction. RESULTS: Lung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability. CONCLUSIONS: SOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis.