Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study / Terapia de Anticoagulação em Pacientes com Fibrilação Atrial não Valvar em Ambiente de Cuidado de Saúde Privado no Brasil: Um Estudo de Mundo Real

Abstract Background: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. Objectives: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. Methods: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. Results: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). Conclusions: More than 60% of the patients were below the desired target and the associated costs were higher.

Resumo Fundamento: A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde. Objetivos: Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos. Métodos: Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5-2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01). Conclusões: Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study.

BACKGROUND: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. OBJECTIVES: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. METHODS: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. RESULTS: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). CONCLUSIONS: More than 60% of the patients were below the desired target and the associated costs were higher.

Fadiga: Um sintoma complexo e seu impacto no câncer e na Insuficiência cardíaca / Fatigue: a complex symptom and its impact on cancer heart failure

Nas doenças crônicas, como câncer e insuficiência cardíaca (IC), a fadiga é um sintoma comum e complexo do ponto de vista etiológico e fisiopatológico, portanto, um tema de relevância na recente área da cardio-oncologia. A fadiga é prevalente em 80-90% dos pacientes oncológicos tratados com quimioterapia e/ou radioterapia e acomete cerca de 50-96% dos indivíduos com IC. A toxicidade atribuída aos quimioterápicos pode determinar o grau de fadiga do paciente e até predizer sua sobrevida. Nas últimas décadas, o avanço das terapias antineoplásicas impactaram substancialmente a sobrevida dos pacientes com câncer, e os riscos dos efeitos lesivos destas terapias ao sistema cardiovascular têm sido cada vez mais descritos. Portanto, a cooperação entre oncologistas e cardiologistas levou ao surgimento da cardio-oncologia e do novo conceito de cardiovigilância. A cardiotoxicidade é uma das complicações clínicas no tratamento do câncer, apresentando como manifestação típica a disfunção sistólica ventricular esquerda. Novas estratégias diagnósticas e terapêuticas têm sido empregadas na cardiovigilância em pacientes com câncer. A fadiga nestes pacientes vem sendo estudada criteriosamente com um olhar multidisciplinar e com o desenvolvimento de escalas visuais para melhor quantificar e correlacionar o seu real impacto na qualidade de vida e sobrevida destes indivíduos. O Pictograma de Fadiga e Escala de Fadiga de Piper são ferramentas cada vez mais utilizadas na pesquisa e na prática clínica. Os mecanismos envolvidos na fadiga, do ponto de vista conceitual, podem ser de origem central (sistema nervoso central) ou periférica (musculoesquelética), ambos os quais podem estar presentes no paciente com câncer. A presente revisão objetiva discutir os novos conceitos na avaliação da fadiga em pacientes oncológicos. Esses conceitos são fundamentais aos profissionais que atuam na emergente área da cardio-oncologia

Impacto inicial de uma clínica de insuficiência cardíaca em hospital cardiológico privado / Initial impact of a disease management program on heart failure in a private cardiology hospital

Fundamentos: A insuficiência cardíaca ainda leva a hospitalizações frequentes apesar dos notáveis avanços terapêuticos. Programas que monitoram e otimizam cuidados têm potencial para melhorar o controle desses pacientes apesar de evidências ainda controversas quanto ao seu real benefício. Objetivos: Caracterizar a população incluída em clínica de insuficiência cardíaca e avaliar a hipótese de benefícios a curto prazo (seis meses). Métodos: Estudo prospectivo que avaliou pacientes hospitalizados com insuficiência cardíaca em hospital privado cardiológico de janeiro a dezembro 2012. Os pacientes foram estratificados em: Grupo 1 – pacientes pré-Programa de cuidados (feito apenas registro de dados); Grupo 2 – pacientes pós-Programa (registro dos mesmos dados junto com intervenções educativas feitas pelo programa de cuidados da Clínica de Insuficiência Cardíaca). Analisadas características da população, indicadores de qualidade e desfechos clínicos. Resultados: Avaliados 762 pacientes, média de idade 70,4±11,0 anos, 56,0 % do sexo masculino. Fração de ejeção reduzida observada em 65,0 %, perfil hemodinâmico B em 66,0 %, etiologia isquêmica em 52,0 % e infecção como fator de descompensação em 29,0 % dos casos. Desfechos analisados nos Grupos 1 e 2, respectivamente: re-hospitalização em 30 dias (13,0 % vs. 9,0 %; p=0,10); tempo médio de hospitalização (9,0 dias vs. 8,4 dias; p=0,4); descompensação por má aderência (17,0 % vs. 10,0 %; p=0,004); mortalidade hospitalar (9,0 % vs. 8,0 %; p=0,7).

Background: Heart failure still leads to frequent hospitalizations despite notable therapeutic advances. Programs that monitor and optimize care have the potential to enhance control of these patients, although evidence of their real benefits is still controversial. Objectives: To describe the population with heart failure included in a Clinical Care Program, assessing the hypothesis of short-term benefits (6 months). Methods: Prospective study assessing heart failure patients in a private cardiology hospital from January to December 2012, divided into two groups: Group 1 – pre-Care Program patients with only data recorded; Group 2 – post-Care Program patients with the same data recorded, together with educational interventions through the Care Program run by the Heart Failure Clinic. The demographic characteristics of the population were analyzed, together with quality indicators and clinical outcomes. Results: Among the 762 patients assessed, the mean age was 70.4±11.0 years, with 56.0% male. Reduced ejection fraction was noted in 65.0%, hemodynamic profile B in 66.0%, ischemic etiology in 52.0% and infection as a decompensation factor in 29.0% of cases. The outcomes analyzed in Groups 1 and 2 were, respectively: hospital readmissions within 30 days (13.0% vs. 9.0%; p=0.1); average length of stay (9.0 days vs. 8.4 days, p=0.4); decompensation due to poor compliance (17.0% vs. 10.0%; p=0.004); and in-hospital mortality (9.0% vs. 8.0%; p=0.7).

Predictive value of myeloperoxidase to identify high risk patients admitted to the hospital with acute chest pain / Valor preditivo da mieloperoxidase na identificação de pacientes de alto risco admitidos por dor torácica aguda

FUNDAMENTO: A mieloperoxidase (MPO) é uma enzima intensamente expressa diante da ativação leucocitária, com múltiplas ações aterogênicas, incluindo a oxidação do colesterol (LDL), e relacionada à instabilização da placa aterosclerótica. É preditora de eventos adversos em indivíduos sadios, coronariopatas ou em investigação de dor torácica. OBJETIVO: Analisar a contribuição da MPO na identificação de pacientes com dor torácica aguda, eletrocardiograma (ECG) sem elevação de segmento ST e com alto risco para eventos adversos intra-hospitalares. MÉTODOS: O nível sérico da MPO foi mensurado na admissão de pacientes com dor torácica aguda, ECG sem elevação de segmento ST e submetidos a protocolo estruturado de investigação. RESULTADOS: De uma coorte de 140 pacientes, 49 (35 por cento) receberam o diagnóstico de síndrome coronariana aguda, tendo sido estabelecido diagnóstico de infarto agudo do miocárdio (troponina I > 1,0 ng/ml) sem elevação de ST em 13 pacientes (9,3 por cento). O melhor ponto de discriminação da MPO para infarto agudo do miocárdio foi identificado em > 100 pM pela curva ROC (AUC = 0,662; IC 95 por cento = 0,532-0,793), que demonstrou elevada sensibilidade (92,3 por cento) e elevado valor preditivo negativo (98,1 por cento), embora com baixa especificidade (40,2 por cento). Na análise multivariada, a MPO mostrou-se a única variável independente para o diagnóstico de infarto agudo do miocárdio em evolução, com razão de chance de 8,04 (p = 0,048). CONCLUSÃO: Em pacientes com dor torácica aguda e sem elevação de ST, a MPO admissional elevada é importante ferramenta preditiva de eventos adversos intra-hospitalares, com razão de chance de oito vezes para o diagnóstico de infarto agudo do miocárdio.

BACKGROUND: Myeloperoxidase (MPO) is a highly expressed enzyme due to leukocyte activation, with multiple atherogenic actions, including LDL cholesterol oxidation, and is related to the instability of atherosclerotic plaque. It is a predictor of adverse events in healthy individuals, patients with heart disease or those undergoing chest pain investigations. OBJECTIVE: To analyze the contribution of MPO to identify patients with acute chest pain, non-ST elevation ECG and at high risk for in-hospital adverse events. METHODS: Patients presenting acute chest pain and a non-ST elevation ECG, were admitted to the hospital and submitted to serum MPO level measurements and a structured examination protocol. RESULTS: From a cohort of 140 patients, 49 (35 percent) were diagnosed with acute coronary syndrome, of which 13 patients (9.3 percent) were diagnosed with non-ST elevation acute myocardial infarction (AMI) (troponin I >1.0 ng/mL). The best MPO cut-off point for AMI was identified as >100 pM using the ROC curve (AUC=0.662; CI 95 percent=0.532-0.793) revealing elevated sensitivity (92.3 percent) and negative predictive value (98.1 percent), however with low specificity (40.2 percent). In the multivariate analysis, MPO proved to be the only independent variable to diagnose AMI in evolution, with an odds ratio of 8.04 (p=0.048). CONCLUSION: In patients with acute chest pain and no ST elevation, high MPO levels upon admission to the hospital are an important tool to predict in-hospital adverse events, with an odds ratio of eight for the diagnosis of AMI.

A first postoperative day predictive score of mortality for cardiac surgery.

PURPOSE: Several prognostic scores for cardiac surgery based on preoperative variables are available. We propose a new one based on pre-and intraoperative and first postoperative day variables for cardiac surgery patients admitted to a surgical intensive care unit. MATERIALS AND METHODS: Classical cohort of data consecutively collected from June 2000 to March 2003 (1,458 patients). Forty-six risk variables were identified. The statistical study comprised univariate analysis followed by logistic regression with receiver operating characteristics (ROC) curve. RESULTS: After logistic regression, the selected variables and respective odds ratios were: age >65 and <75 years (2.05); age >/=75 years (4.79); left atrial diameter >45 mm (2.58); preoperative creatinine >2 mg/dL (4.84); and cardiopulmonary bypass time >/=180 min (4.93+/-2). The first postoperative day variables were as follows: the worst PaO(2)/FiO(2) <100 (9.47); epinephrine or norepinephrine dose >/=0.1 microg/kg/min (6.78); and mechanical ventilation time >12 h (2.24). The area under the ROC curve was 0.84. CONCLUSION: The score shows the strength of first postoperative day variables, probably related to intraoperative conditions. It also evidences the importance of left atrial diameter as a new marker of preoperative risk.

Predictive value of myeloperoxidase to identify high risk patients admitted to the hospital with acute chest pain.

BACKGROUND: Myeloperoxidase (MPO) is a highly expressed enzyme due to leukocyte activation, with multiple atherogenic actions, including LDL cholesterol oxidation, and is related to the instability of atherosclerotic plaque. It is a predictor of adverse events in healthy individuals, patients with heart disease or those undergoing chest pain investigations. OBJECTIVE: To analyze the contribution of MPO to identify patients with acute chest pain, non-ST elevation ECG and at high risk for in-hospital adverse events. METHODS: Patients presenting acute chest pain and a non-ST elevation ECG, were admitted to the hospital and submitted to serum MPO level measurements and a structured examination protocol. RESULTS: From a cohort of 140 patients, 49 (35%) were diagnosed with acute coronary syndrome, of which 13 patients (9.3%) were diagnosed with non-ST elevation acute myocardial infarction (AMI) (troponin I >1.0 ng/mL). The best MPO cut-off point for AMI was identified as >100 pM using the ROC curve (AUC=0.662; CI 95%=0.532-0.793) revealing elevated sensitivity (92.3%) and negative predictive value (98.1%), however with low specificity (40.2%). In the multivariate analysis, MPO proved to be the only independent variable to diagnose AMI in evolution, with an odds ratio of 8.04 (p=0.048). CONCLUSION: In patients with acute chest pain and no ST elevation, high MPO levels upon admission to the hospital are an important tool to predict in-hospital adverse events, with an odds ratio of eight for the diagnosis of AMI.

Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: a prospective observational study.

INTRODUCTION: Cardiovascular surgery with cardiopulmonary bypass (CPB) has improved in past decades, but inflammatory activation in this setting is still unpredictable and is associated with several postoperative complications. Perioperative levels of macrophage migration inhibitory factor (MIF) and other inflammatory mediators could be implicated in adverse outcomes in cardiac surgery. METHODS: Serum levels of MIF, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, IL-6 and IL-10 from 93 patients subjected to CPB were measured by enzyme-linked immunosorbent assay and compared with specific and global postoperative organ dysfunctions through multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA). RESULTS: Most of the cytokines measured had a peak of production between 3 and 6 hours after CPB, but maximum levels of MIF occurred earlier, at the cessation of CPB. Among specific organ dysfunctions, the most frequent was hematological, occurring in 82% of the patients. Circulatory impairment was observed in 73.1% of the patients, and 51% of these needed inotropics or vasopressors within the first 24 hours after surgery. The third most frequent dysfunction was pulmonary, occurring in 48.4% of the patients. Preoperative levels of MIF showed a relevant direct correlation with the intensity of global organ dysfunction measured by SOFA (rho = 0.46, p < 0.001) and MODS (rho = 0.50, p < 0.001) on the third day after surgery. MCP-1 production was associated with postoperative thrombocytopenia, and MIF was related to the use of a high dose of vasopressors in patients with cardiovascular impairment and also to lower values of the ratio of partial arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) registered in the first 24 hours after CPB. CONCLUSION: Despite the multifactorial nature of specific or multiple organ dysfunctions, MIF should be explored as a predicting factor of organ dysfunction, or even as a potential therapeutic target in decreasing postoperative complications.

Prospecção de biomarcadores inflamatórios de síndrome coronariana aguda - resultados preliminares / Prospecting of inflamatory biomarkers in acute coronary syndrome - preliminary results

Fundamentos: Numerosas substâncias têm sido exploradas como preditores de risco em doença arterial coronariana (DARC), mas a literatura ainda carece de indicadores de síndrome coronariana aguda (SCA).Objetivos: Este estudo piloto visa a descrever níveis circulantes do fator de inibição da migração de macrófagos (MIF), da fração solúvel de ligante de CD40 (sCD40L) e da interleucina 6 (IL-6) numa amostra de pacientes sob suspeita de SCA, no sentido de explorar seu potencial como ferramentas diagnósticas.Métodos: Num período de 6 meses, uma série de pacientes atendidos em unidade de dor torácica, com e sem critérios diagnósticos de SCA, tiveram amonstras de sangue venoso periféricos coletadas com o propósito de medir e comparar a produção das citocinas nos dois grupos...

Macrophage migration inhibitory factor is associated with positive cultures in patients with sepsis after cardiac surgery.

This prospective consecutive observational study describes the blood levels of macrophage migration inhibitory factor (MIF), other cytokines, and markers of acute-phase response in 49 consecutive patients who developed the clinical syndrome of sepsis after cardiac surgery. Before starting antimicrobial treatment, all patients underwent microbiologic screening, and blood samples were collected. These samples subsequently were assayed for MIF, macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and -10, procalcitonin (PCT), and C-reactive protein (CRP). Patients with positive cultures (n = 25) had a higher mortality (P = 0.046) and higher levels of MIF (P < 0.001) than those with negative cultures (n = 24). We could not detect significant difference between the groups concerning the levels of CRP, PCT, IL6, IL10, MCP-1, or TNF-alpha. MIF levels showed an area under receiver operator curve of 0.823 for the prediction of culture-proven bacterial infection, with the best cut-off value at 988.5 pg/mL. In conclusion, circulating levels of MIF could be indicated as a valuable marker of microbiologically documented sepsis in patients after cardiac surgery, which suggests that MIF may be prospectively explored as a useful diagnostic tool in this setting.

Circulating levels of macrophage migration inhibitory factor are associated with mild pulmonary dysfunction after cardiopulmonary bypass.

Macrophage migration inhibitory factor (MIF) is a central mediator of inflammatory response and acute lung injury that is secreted in response to corticosteroids. A rise in systemic MIF levels was described after cardiac surgery in steroid-treated patients. This study aimed to investigate the circulating levels of MIF and the possible relationship of this cytokine to pulmonary dysfunction after cardiopulmonary bypass (CPB). We included 74 patients without previous organ dysfunction undergoing elective coronary artery bypass surgery (CABS). The same team performed all CABS via a standard technique adding methylprednisolone (15 mg/kg) to the CPB priming solution (Group MP, n = 37). In the remaining patients (Group NS, n = 37), methylprednisolone was withdrawn from the CPB priming. MIF, C-reactive protein (CRP), and total C3 were assayed in peripheral blood sampled immediately before anesthesia induction and 3, 6, and 24 h post-CPB. Preoperative risk scores and peri- and postoperative variables were documented. Postoperative kinetics of MIF and C3 were similar for both groups. Levels of CRP 24 h post-CPB were higher in Group MP (P = 0.003). Higher MIF levels were detected 6 h post-CPB, and returned to preoperative levels 24 h after CPB. MIF levels 6 h post-CPB were inversely related to the postoperative PaO2/FiO2 ratio (P = 0.0021) and were directly related to the duration of mechanical ventilation (P = 0.014). Perioperative use of methylprednisolone did not modify the MIF response to CPB, but it was related to an enhanced acute phase response. Higher circulating MIF levels 6 h post-CPB were associated with worse postoperative pulmonary short-course outcome.

Alterações sequenciais dos níneis séricos de fator inibidor da migração de macrófagos em pacientes submetidos à cirurgia de revascularização miocárdica / Sequential variations on macrophage migration inhibitory factor (MIF) blood levels in patients submitted to coronary artery bypass surgery

Este estudo define níveis de fator inibidor da migração de macrófagos (MIF) após cirurgia de revascularização miocárdica (RM), suas relações com o uso de esteróides e com a disfunção orgânica pós-operatória. Mediram-se níveis séricos de MIF em pacientes operados sob uso de metilprednisolona (n=37) ou não (n=37). Os níveis máximos ocorreram entre três e seis horas após o procedimento e correlacionaram-se com a relação PaO2/FiO2 e à duração da ventilação mecânica pós-operatória, mas não à intensidade de disfunção orgânica múltipla pós-operatória / This study defines macrophage migration inhibitory factor (MIF) blood levels following coronary artery bypass surgery (CABS) and their relation to steroid treatment and postoperative organ dysfunction. Patients operated under methylprednisolone treatment (n=37) or not (n=37), had MIF sequentially assayed. Maximum levels were noted between three and six hours after the procedure. These levels of MIF were correlated to postoperative PaO2/FiO2 ratio and the duration of mechanical ventilation, but not to multiple organ dysfunction score. We concluded that, despite steroid administration, MIF rises after CABS and its levels are correlated to postoperative pulmonary dysfunction...