Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction. / Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio.

BACKGROUND: Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. OBJECTIVE: Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. METHODS: Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. RESULTS: During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. CONCLUSION: The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

FUNDAMENTO: O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). OBJETIVO: Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. MÉTODOS: Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. RESULTADOS: Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. CONCLUSÃO: O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Alterações Hematológicas durante um Período de Sete Dias de Internação em Pacientes com Infarto Agudo do Miocárdio / Hematological Changes during Seven Days of Hospitalization in Patients with Acute Myocardial Infarction

Resumo Fundamento O infarto agudo do miocárdio é uma das principais causas de mortalidade em todo o mundo e a formação de placa aterosclerótica é o principal mecanismo fisiopatológico, que resulta em inflamação crônica e induz a maturação eritrocitária, podendo causar aumento no índice de amplitude de distribuição dos glóbulos vermelhos (RDW). Objetivo Avaliar o papel do índice de anisocitose em pacientes com infarto agudo do miocárdio em ambos os tipos de infarto como preditor de gravidade. Métodos Os pacientes foram incluídos no estudo de acordo com os critérios de inclusão e exclusão, seguindo a rotina hospitalar baseada na história clínica e laboratorial. As análises estatísticas foram realizadas de acordo com cada variável. Chegou-se a todas as conclusões considerando o nível de significância de 5%. Resultados Durante o período de acompanhamento, nos 349 pacientes analisados, a taxa de mortalidade esteve associada às variáveis RDW (CV) e RDW (SD). Nos pacientes que foram a óbito, notou-se aumento, conforme demonstrado no modelo multivariado, nos efeitos de um infarto agudo do miocárdio com supradesnivelamento do segmento ST e RDW, ajustado para fatores de confusão (valor-p = 0,03 e 0,04). Em contrapartida, o número total de eritrócitos (valor-p = 0,00) e hemoglobina (valor-p = 0,03) apresentou diminuição durante a internação de pacientes graves. Conclusão O índice de anisocitose foi fator preditivo de mortalidade e pode ser utilizado como indicador de pior prognóstico em pacientes com infarto agudo do miocárdio.

Abstract Background Acute myocardial infarction is a major cause of mortality worldwide, and atherosclerotic plaque formation is the main pathophysiological mechanism, which results in chronic inflammation that induces erythrocyte maturation and may cause an increase in the red cell distribution width (RDW) index. Objective Evaluate the role of the anisocytosis index in patients with acute myocardial infarction in both types of infarctions as a predictor of severity. Methods Patients were included in the study according to the inclusion/exclusion criteria, following the hospital routine based on their clinical and laboratory history. Statistical analyzes were performed according to each variable. All conclusions were drawn considering the significance level of 5%. Results During the follow-up period, in the 349 patients analyzed, the mortality rate was associated with the variables RDW (CV) and RDW (SD), in those patients who died, an increase was noted, as demonstrated in the multivariate model, for the effects of an acute ST elevation myocardial infarction and the RDW, adjusted for confounding factors (p-value = 0.03 and 0.04). In contrast, the total number of erythrocytes (p-value = 0.00) and hemoglobin (p-value = 0.03) showed a decrease during severe patients' hospitalization. Conclusion The anisocytosis index was a predictive factor of mortality and can be used as an indicator of worse prognosis in patients with acute myocardial infarction.

Performance of a Hematological Scoring System in Predicting All-Cause Mortality in Patients with Acute Myocardial Infarction

Abstract Background: The presence of nucleated red blood cells (NRBCs) and increases in mean platelet volume (MPV) and neutrophil to lymphocyte ratio (NLR) in peripheral circulation are associated with poorer prognosis in patients with acute coronary disease. Objective: We developed a scoring system for in-hospital surveillance of all-cause mortality using hematological laboratory parameters in patients with acute myocardial infarction (AMI). Methods: Patients admitted for AMI were recruited in this prospective study. Exclusion criteria were age younger than 18 years, glucocorticoid therapy, cancer or hematological diseases and readmissions. NRBCs, MPV and NLR were measured during hospitalization. The scoring system was developed in three steps: first, the magnitude of the association of clinical and laboratory parameters with in-hospital mortality was measured by odds ratio (OR), second, a multivariate logistic regression model was conducted with all variables significantly (p < 0.05) associated with the outcome, and third, a β-coefficient was estimated by multivariate logistic regression with hematological parameters with a p < 0.05. Results: A total of 466 patients (mean age were 64.2 ± 12.8 years, 61.6% male) were included in this study. A hematological scoring system ranging from 0 to 49, where higher values were associated with higher risk of in-hospital death. The best performance was registered for a cut-off value of 26 with sensitivity of 89.1% and specificity of 67.2%, positive predictive value of 26.8% (95% CI: 0.204 - 0.332) and negative predictive value of 97.9% (95% CI: 0.962 - 0.996). The area under the curve for the scoring system was 0.868 (95% CI: 0.818 - 0.918). Conclusions: Here we propose a hematological scoring system for surveillance tool during hospitalization of patients with acute myocardial infarction. Based on total blood count parameters, the instrument can evaluate inflammation and hypoxemia due to in-hospital complications and, consequently, predict in-hospital mortality.

Prognostic value of hematological parameters in patients with acute myocardial infarction: Intrahospital outcomes.

BACKGROUND: The intensity of the inflammatory response and hemodynamic repercussion in acute myocardial infarction causing the presence in the peripheral circulation of nucleated red blood cells (NRBCs), increases in mean platelet volume (MPV) and neutrophil to lymphocyte ratio (NLR) are associated with a poorer prognosis. The aim of this study was to assess the role of these hematological biomarkers as predictors of all causes of mortality during the hospitalization of patients with acute myocardial infarction. METHODS: Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio were measured daily during the hospitalization of the patients with acute myocardial infarction. We excluded patients younger than 18 years, on glucocorticoid therapy, with cancer or hematological diseases and those that were readmitted after hospital discharge. We performed a multiple logistic analysis to identify independent predictors of mortality. RESULTS: We included 466 patients (mean age 64.2 ± 12.8 years, 61.6% male). The prevalence of NRBCs in the sample was 9.1% (42 patients), with levels > 200/µL in 27 patients (5.8%). The mean MPV value was 10.9 ±0,9 and the mean NLR value was 3.71 (2,38; 5,72). In a multivariate analysis of serum NRBCs (HR 2.42, 95% CI: 1.35-4.36, p = 0.003), MPV (HR 2.97, 95% CI: 1.15-7.67, p = 0.024) and NLR (HR 5.02, 95% CI: 1.68-15.0, p = 0.004). The presence in the peripheral blood of NRBCs, increased in mean platelet volume and neutrophil to lymphocyte ratio were associated with higher mortality. CONCLUSIONS: Nucleated red blood cells, mean platelet volume and neutrophil to lymphocyte ratio are independent predictors of intrahospital mortality. Therefore, an important tool in intrahospital clinical surveillance.

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study.

BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients. METHODS: NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality. RESULTS: We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4-11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45-10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63-6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01). CONCLUSIONS: NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.

Chronic treatment with Sildenafil has no effect on folliculogenesis or fertility in C57BL/6 and C57BL/6 knockout for iNOS mice.

Sildenafil is an important phosphodiesterase inhibitor used to treat a range of diseases, including cardiovascular disease, prostatic hyperplasia and pulmonary hypertension. Its main mechanism of action is the inhibition of phosphodiesterase 5, leading to increased intracellular cyclic guanosine 3',5'-monophosphate. This second messenger plays an interesting role in the reproductive tract. The aim of the present study was to evaluate the effect of Sildenafil on folliculogenesis and fertility in mice. To do so, C57BL/6 wild-type mice and inducible nitric oxide synthase knockout (iNOS(-/-)) mice were treated with Sildenafil, and reproductive variables were evaluated. The treated and control animals underwent estrous cycle and fertility assay. Lipid profile, serum nitric oxide levels and the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and guanylate cyclase were evaluated. Additionally, ovaries were submitted to histological and morphological analysis. The findings demonstrated that chronic treatment with Sildenafil had no effect on folliculogenesis or fertility in C57BL/6 mice, suggesting that this drug can be safely used by women of childbearing age.

Implementation, validation and review of a critical values list in a cardiac emergency room / Implantação, validação e revisão da lista de valores críticos em um pronto-socorro cardiológico

Introduction: Laboratory critical values (CV) can indicate threatening conditions that require rapid clinical intervention. The aim of this study was to implement, validate and review a critical values list (CVL) at Pronto-Socorro Cardiológico de Pernambuco - Universidade de Pernambuco (PROCAPE-UPE). Method: This study was conducted between 2011 and 2013. To formulate the CVL, laboratory tests performed at PROCAPE were analyzed and compared with those of the Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the College of American Pathologists (CAP). A draft CVL was validated by physicians; staff training and the standard operating procedure were developed covering the entire clinical analysis laboratory, in order to formalize the procedure of critical result reporting. The CVL was updated every six months. Results: Changes were made in CV intervals for the measurement of total serum calcium, serum sodium, serum potassium, the international normalized ratio (INR) and total leukocyte count. Thyroid-stimulating hormone (TSH) was also included in the CVL. In the pediatric CVL, dosages of serum sodium and INR were included, and a change in the value of serum potassium was made. Thus, periodic reviews of CVL allowed greater adequacy to the needs of the study population and avoided overloading the notification process. Conclusion: Clinical laboratories must be responsible for the implementation, validation and review of their CVL to ensure patients’ health. .

Introdução: Valores críticos (VC) laboratoriais podem ser indicativos de condições de risco de morte que requerem intervenção clínica rápida. O objetivo deste estudo foi implantar, validar e revisar uma lista de valores críticos (LVC) no Pronto-Socorro Cardiológico Universitário de Pernambuco-Universidade de Pernambuco (PROCAPE-UPE). Método: Este trabalho foi realizado no período de 2011 a 2013. Para elaborar a LVC, os testes laboratoriais realizados no PROCAPE foram analisados e comparados com os dos jornais da Federação Internacional de Química Clínica e Medicina Laboratorial (IFCC) e do Colégio Americano de Patologistas (CAP). Após a elaboração da LVC, ela foi validada por médicos; treinamentos e procedimento operacional padrão foram desenvolvidos abrangendo todo o laboratório de análises clínicas, com o intuito de formalizar o procedimento de comunicação de resultados críticos. A LVC foi revisada a cada seis meses. Resultados: Foram realizadas modificações nos intervalos de VC na dosagem de cálcio sérico total, sódio sérico, potássio sérico, no índice internacional normalizado (INR) e na contagem total de leucócitos. Também foi incluído na LVC o hormônio estimulante de tireoide (TSH). Na LVC exclusiva da pediatria, foi incluída a dosagem de sódio sérico e o INR, e uma alteração no valor do potássio sérico foi realizada. Assim, uma avaliação periódica da LVC possibilitou maior adequação às necessidades da população de estudo e evitou sobrecarga no processo de notificação. Conclusão: Faz-se necessário que os laboratórios de análises clínicas sejam responsáveis pela implantação, validação ...

Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.

Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism.

[Homocysteinemia in polycystic ovary syndrome women]. / Homocisteinemia em mulheres com síndrome dos ovários policísticos.

PURPOSE: To compare serum homocysteine levels in polycystic ovary syndrome (PCOS) and non-PCOS women and correlate them with clinical, hormonal and metabolic parameters. METHODS: Transverse study with carried out on 110 women, including 56 with PCOS and 54 normal controls. Patients were submitted to anamnesis, physical examination and pelvic sonograms and to the determination of homocysteine, C-reactive protein (CRP), glucose insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free thyroxin (Free T4), prolactin, and testosterone. For the statistical analysis, we used the Student's t test, Pearson's product-moment correlation coefficient and the chi(2) test. The "enter" method was used to determine independent association between variables. RESULTS: There was a significant increase in the average serum homocysteine levels in the group of patients with PCOS compared to controls (5.97+/-2.95 versus 5,17+/-1.33 micromol/L; p=0,015). As expected, since they are affected by PCOS, values of body mass index (BMI), waist circumference, total cholesterol, HDL cholesterol, triglycerides, insulin and HOMA were significantly different between groups. Serum homocysteine levels, BMI and PCOS were correlated. Multivariate analysis showed that PCOS, by itself, does not correlate with high serum homocysteine levels. CONCLUSIONS: PCOS women have significantly higher serum levels of homocysteine that may increase their risk for cardiovascular disease. However, other intrinsic PCOS-related factors, not identified in this study, may be responsible for this alteration.

Effect of maternal diet rich in omega-6 and omega-9 fatty acids on the liver of LDL receptor-deficient mouse offspring.

BACKGROUND: Omega-6 fatty acids are important to fetal development. However, during gestation/lactation, these fatty acids may contribute toward the development of fat tissue. Omega-9 fatty acids are associated with a reduction in serum lipids and protection from liver disease. OBJECTIVES: The present study investigated the effect of the maternal intake of omega-6 and omega-9 in hypercholesterolemic mothers on the liver of the offspring. METHODS: LDL receptor-deficient mice were fed a diet rich in either omega-6 (E6D) or omega-9 (E9D) for 45 days prior to mating and until the birth of the offspring, evaluating the effect on the offspring liver in comparison to a standard diet (STD). RESULTS: Mothers fed with the E6D experienced an increase in total cholesterol (TC) and the offspring exhibited an increase in TC, hepatic triglycerides (TG), and CC-chemokine ligand (CCL)2/monocyte chemoattractant protein (MCP)-1 as well as a reduction in HDL. Histological analysis on this group revealed steatosis, leukocyte infiltrate, and increased CCL2/MCP-1 expression. The ultrastructural analysis revealed hepatocytes with lipid droplets and myofibroblasts. The offspring of mothers fed the standard diet exhibited low serum TC, but microvesicular steatosis was observed. The offspring of mothers fed the E9D exhibited lower serum and hepatic TG as well as higher LDL in comparison to the other diets. The histological analyses revealed lower steatosis and leukocyte infiltrate. CONCLUSIONS: The findings suggest that hypercholesterolemic mothers with a diet rich in omega-6 fatty acids predispose their offspring to steatohepatitis, whereas a diet rich in omega-9 has a protective effect.

Homocisteinemia em mulheres com síndrome dos ovários policísticos / Homocysteinemia in polycystic ovary syndrome women

Objetivos: comparar os níveis sanguíneos de homocisteína em mulheres com e sem a síndrome dos ovários policísticos (SOP) e correlacioná-los com os parâmetros clínicos, hormonais e metabólicos. Métodos: estudo tipo corte transversal com 110 mulheres: 56 com SOP e 54 controles normais. As pacientes foram submetidas à anamnese, exame físico e ultrassonografia pélvica, dosagens de homocisteína, da proteína C reativa (PCR), glicose, insulina, hormônio folículo-estimulante (FSH), hormônio luteinizante (LH), hormônio tireoide-estimulante (TSH), tiroxina livre (T4L), prolactina e testosterona.. Para análise estatística, foram usados os testes t de Student, χ2 e a correlação de Pearson. A realização da análise multivariada, pelo método "enter", foi utilizada para verificar a associação independente entre as variáveis. Resultados: encontrou-se um aumento significativo na média dos níveis plasmáticos de homocisteína nas pacientes com SOP quando comparadas ao Grupo Controle (5,9±2,9 versus 5,1±1,3 µmol/L; p=0,01). Como era esperado, por fazerem parte do quadro clínico da SOP, o índice de massa corpórea, circunferência abdominal, colesterol total, colesterol HDL, triglicerídeos, insulina e HOMA também se mostraram com diferenças significativas entre os dois grupos. Houve correlação da SOP e do IMC com os níveis de homocisteína. A análise multivariada mostrou que a SOP por si só não se correlaciona com altos níveis de homocisteína. Conclusões: pacientes com SOP estão expostas a níveis significativamente altos de homocisteína, porém outros fatores intrínsecos à síndrome, e não identificados neste estudo, seriam os responsáveis por esta alteração.

Purpose: to compare serum homocysteine levels in polycystic ovary syndrome (PCOS) and non-PCOS women and correlate them with clinical, hormonal and metabolic parameters. Methods: transverse study with carried out on 110 women, including 56 with PCOS and 54 normal controls. Patients were submitted to anamnesis, physical examination and pelvic sonograms and to the determination of homocysteine, C-reactive protein (CRP), glucose insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free thyroxin (Free T4), prolactin, and testosterone. For the statistical analysis, we used the Student's t test, Pearson's product-moment correlation coefficient and the χ2 test. The "enter" method was used to determine independent association between variables. Results: there was a significant increase in the average serum homocysteine levels in the group of patients with PCOS compared to controls (5.97±2.95 versus 5,17±1.33 µmol/L; p=0,015). As expected, since they are affected by PCOS, values of body mass index (BMI), waist circumference, total cholesterol, HDL cholesterol, triglycerides, insulin and HOMA were significantly different between groups. Serum homocysteine levels, BMI and PCOS were correlated. Multivariate analysis showed that PCOS, by itself, does not correlate with high serum homocysteine levels. Conclusions: PCOS women have significantly higher serum levels of homocysteine that may increase their risk for cardiovascular disease. However, other intrinsic PCOS-related factors, not identified in this study, may be responsible for this alteration.

Changes in mouse Leydig cells ultrastructure and testosterone secretion after diethylcarbamazine administration.

Diethylcarbamazine (DEC) has been proven to be highly effective against lymphatic filariasis, although its effect on vertebrate cells remains uncertain. Mice Leydig cells after treatment with 200mg/kg of DEC for 12 days showed numerous lipid droplets, degenerated mitochondria, residual bodies and several giant whorl-like smooth endoplasmic reticulum, some of them encircling large lipids droplets. Treatment with lower dosages showed similar alterations on Leydig cells and the morphological effects decreased directly proportional to the drug concentration. Serum testosterone levels were significantly lower only in 200 mg/kg DEC-treated group when compared to the controls. However, no significant changes were observed in the pregnancy rates and offspring number of DEC-treated male-mated female mice in any doses studied. The results obtained in the present study are consistent with the hypothesis that DEC has some effects on mice Leydig cells, although they were not sufficient enough to interfere with the rodent fertility.