Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters. / Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca.

BACKGROUND: Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. OBJECTIVES: This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. METHODS: Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. RESULTS: Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. CONCLUSION: Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.

FUNDAMENTO: A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). OBJETIVOS: Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. MÉTODOS: Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. RESULTADOS: Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. CONCLUSÃO: A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos.

Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca / Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters

Resumo Fundamento A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). Objetivos Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. Métodos Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. Resultados Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. Conclusão A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos

Abstract Background Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. Objectives This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. Methods Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. Results Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. Conclusion Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.

Atherosclerosis severity in patients with familial hypercholesterolemia: The role of T and B lymphocytes.

Background and aims: Familial hypercholesterolemia (FH) is characterized by lifelong exposure to high LDL-c concentrations and premature atherosclerotic cardiovascular disease; nevertheless, disease severity can be heterogeneous.We aimed at evaluating if the immune-inflammatory system could modulate atherosclerosis burden in FH. Methods: From a cohort of subjects with confirmed FH (Dutch Lipid Clinic Network and genotype), 92 patients receiving high-intensity lipid-lowering therapy (statin ± ezetimibe) were included. The extension and severity of coronary atherosclerosis was assessed by standardized reporting systems (CAD-RADS) for coronary computed tomography angiography (CCTA) and coronary artery calcium (CAC) scores. Lipids, apolipoproteins, anti-oxLDL and anti-apolipoprotein B-D peptide (anti-ApoB-D) autoantibodies (IgM and IgG), lymphocytes subtypes, platelet, monocyte and endothelial microparticles (MP), IgM levels (circulating or produced by B1 cells) and cytokines in the supernatant of cultured cells were determined. Multiple linear regression models evaluated associations of these biomarkers with CAC and CAD-RADS scores. Results: In univariate analysis CAC correlated with age, systolic blood pressure, TCD4+ cells, and titers of IgM anti-ApoB-D. In multiple linear regression [ANOVA F = 2.976; p = 0.024; R2 = 0.082), CD4+T lymphocytes (B = 35.289; beta = 0.277; p = 0.010; 95%CI for B 8.727 to 61.851), was independently associated with CAC. CAD-RADS correlated with age, systolic blood pressure, titers of IgM anti-ApoB-D, and endothelial MP in univariate analysis. In multiple linear regression, [ANOVA F = 2.790; p = 0.032; R2 = 0.119), only age (B = 0.027; beta = 0.234; p = 0.049; 95% CI for B 0.000 to 0.053) was independent predictor. Conclusions: In subjects with FH, under high-intensity lipid-lowering therapy, age and CD4+T cells were associated to atherosclerosis burden.

Better Response to Influenza Virus Vaccination in Physically Trained Older Adults Is Associated With Reductions of Cytomegalovirus-Specific Immunoglobulins as Well as Improvements in the Inflammatory and CD8+ T-Cell Profiles.

Chronic cytomegalovirus (CMV) infection is a trigger factor for the development of immunosenescence and negatively impacts the immune response to influenza virus vaccination (IVV) in older adults. However, the role of physical exercise training in this context is unknown. Thus, the aim of this study was to investigate whether the regular practice of combined exercise training can improve the specific antibody response to IVV in CMV-seropositive older adults. Eighty older adults were distributed into two groups-non-practitioners (NP, n = 31, age = 74.06 ± 6.4 years) and practitioners of combined exercise training (CET, n = 49, age = 71.7 ± 5.8 years)-for at least 12 months. Both volunteer groups were submitted to IVV and blood samples were collected before (pre) and 30 days after (post) the vaccination. Concerning the specific antibody response to IVV, higher serum levels of specific immunoglobulin A (IgA) were found in the CET group post- than pre-vaccination (p < 0.01), whereas higher levels of specific immunoglobulin M (IgM) were observed both in the NP (p < 0.05) and CET (p < 0.001) groups post-vaccination as compared to the pre-vaccination values. Serum levels of specific immunoglobulin G (IgG) for IVV and CMV, as well as interleukin 6 (IL-6) and IL-10, were similar between the time points evaluated. However, the IL-10/IL-6 ratio post-vaccination was higher (p < 0.05) in the CET group than that before vaccination. Negative correlations were observed between the specific IgG levels for IVV and CMV only in the CET group, both pre- and post-vaccination. In addition, negative correlations were found between IL-10 and specific IgG for CMV in all volunteer groups pre- and post-vaccination, whereas a positive correlation between IL-10 and specific-IgG for IVV pre- and post-vaccination was observed in the CET group. In addition, with the hemagglutination inhibition (HAI) assay, it was found that 32.2% of the NP group and 32.6% of the CET group were responders to IVV and displayed reductions in the CMV serostatus (p < 0.05 and p < 0.001, respectively) and increases in naive and effector CD8+ T cells post-vaccination (p < 0.01). However, only the responders from the CET group showed significant reductions in the ratio of effector to naive CD8+ T cells (p < 0.05) and increased IL-10 levels post-vaccination (p < 0.001). In summary, this study demonstrates that the improvement in the response to IVV in CMV-seropositive older adults was related to an anti-inflammatory status and enhancement of naive CD8+ T cells, particularly associated with regular practice of CET.

Main differences between two highly effective lipid-lowering therapies in subclasses of lipoproteins in patients with acute myocardial infarction.

BACKGROUND: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test). RESULTS: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin. CONCLUSIONS: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.

Principles for Organizing the Flow of Automation in the Clinical Laboratory.

In the healthcare industry, there is strong pressure to reduce costs that, together with several factors, have contributed significantly to the scarcity of resources in the health system. Besides, health systems will continue to be under pressure to serve their users. Therefore, it is necessary to develop an innovative model that combines quality, sustainability, and increased access. For the success of any decision-making process regarding the purchase, rental, or lending of automation equipment, not only costing assessments are required, but above all, alignment with the institutional strategy, ideally conceptualized in an organization model by optimized workflows and work processes, in order to, ultimately, be able to remain profitable and competitive in the current global business environment, which requires continuous improvement in levels of productivity, quality, agility, and service provision.

Alterações Precoces nas Interleucinas Circulantes e no Risco Inflamatório Residual após Infarto Agudo do Miocárdio / Early Changes in Circulating Interleukins and Residual Inflammatory Risk After Acute Myocardial Infarction

Resumo Fundamento Pacientes com infarto agudo do miocárdio podem apresentar uma grande área infartada e disfunção ventricular mesmo com trombólise e revascularização precoces. Objetivo Investigar o comportamento das citocinas circulantes em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) e a relação delas com a função ventricular. Métodos No estudo BATTLE-AMI (Avaliação dos Linfócitos Tipos B e T no Infarto Agudo do Miocárdio), os pacientes com IAMCSST foram tratados com uma estratégia farmacoinvasiva. Os níveis de citocinas (IL-1β, IL-4, IL-6, IL-10 e IL-18) no plasma foram testados através de ensaio de imunoadsorção enzimática (ELISA) no início do estudo e após 30 dias. A massa infartada e a fração de ejeção ventricular esquerda (FEVE) foram examinadas por ressonância magnética cardíaca 3-T. Valores de p menores que 0,05 foram considerados significativos. Resultados Na comparação com o início do estudo, níveis mais baixos foram detectados para IL-1β (p = 0,028) e IL-18 (p < 0,0001) após 30 dias do IAMCSST, enquanto níveis mais altos foram observados para IL-4 (p = 0,001) e IL-10 (p < 0,0001) no mesmo momento. Em contrapartida, nenhuma mudança foi detectada nos níveis de IL-6 (p = 0,63). Os níveis da proteína C-reativa de alta sensibilidade e de IL-6 se correlacionaram no início do estudo (rho = 0,45, p < 0,0001) e 30 dias após o IAMCSST (rho = 0,29, p = 0,009). No início do estudo, a correlação entre os níveis de IL-6 e FEVE também foi observada (rho = -0,50, p = 0,004). Conclusões Durante o primeiro mês pós-infarto agudo do miocárdio, observamos uma melhora significativa no balanço das citocinas pró e anti-inflamatórias, exceto da IL-6. Esses achados sugerem risco inflamatório residual. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Patients with acute myocardial infarction may have a large infarcted area and ventricular dysfunction despite early thrombolysis and revascularization. Objective To investigate the behavior of circulating cytokines in patients with ST-segment elevation myocardial infarction (STEMI) and their relationship with ventricular function. Methods In the BATTLE-AMI (B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction) trial, patients with STEMI were treated with a pharmacoinvasive strategy. The plasma levels of cytokines (IL-1 β , IL-4, IL-6, IL-10, and IL-18) were tested using enzyme-linked immunosorbent assay (ELISA) at baseline and after 30 days. Infarcted mass and left ventricular ejection fraction (LVEF) were examined by 3-T cardiac magnetic resonance imaging. All p-values < 0.05 were considered statistically significant. Results Compared to baseline, lower levels were detected for IL-1 β (p = 0.028) and IL-18 (p < 0.0001) 30 days after STEMI, whereas higher levels were observed for IL-4 (p = 0.001) and IL-10 (p < 0.0001) at that time point. Conversely, no changes were detected for IL-6 levels (p = 0.63). The levels of high-sensitivity C-reactive protein and IL-6 correlated at baseline (rho = 0.45, p < 0.0001) and 30 days after STEMI (rho = 0.29, p = 0.009). At baseline, correlation between IL-6 levels and LVEF was also observed (rho = -0.50, p = 0.004). Conclusions During the first month post-MI, we observed a marked improvement in the balance of pro- and anti-inflammatory cytokines, except for IL-6. These findings suggest residual inflammatory risk. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Early Changes in Circulating Interleukins and Residual Inflammatory Risk After Acute Myocardial Infarction. / Alterações Precoces nas Interleucinas Circulantes e no Risco Inflamatório Residual após Infarto Agudo do Miocárdio.

BACKGROUND: Patients with acute myocardial infarction may have a large infarcted area and ventricular dysfunction despite early thrombolysis and revascularization. OBJECTIVE: To investigate the behavior of circulating cytokines in patients with ST-segment elevation myocardial infarction (STEMI) and their relationship with ventricular function. METHODS: In the BATTLE-AMI (B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction) trial, patients with STEMI were treated with a pharmacoinvasive strategy. The plasma levels of cytokines (IL-1 ß , IL-4, IL-6, IL-10, and IL-18) were tested using enzyme-linked immunosorbent assay (ELISA) at baseline and after 30 days. Infarcted mass and left ventricular ejection fraction (LVEF) were examined by 3-T cardiac magnetic resonance imaging. All p-values < 0.05 were considered statistically significant. RESULTS: Compared to baseline, lower levels were detected for IL-1 ß (p = 0.028) and IL-18 (p < 0.0001) 30 days after STEMI, whereas higher levels were observed for IL-4 (p = 0.001) and IL-10 (p < 0.0001) at that time point. Conversely, no changes were detected for IL-6 levels (p = 0.63). The levels of high-sensitivity C-reactive protein and IL-6 correlated at baseline (rho = 0.45, p < 0.0001) and 30 days after STEMI (rho = 0.29, p = 0.009). At baseline, correlation between IL-6 levels and LVEF was also observed (rho = -0.50, p = 0.004). CONCLUSIONS: During the first month post-MI, we observed a marked improvement in the balance of pro- and anti-inflammatory cytokines, except for IL-6. These findings suggest residual inflammatory risk. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: Pacientes com infarto agudo do miocárdio podem apresentar uma grande área infartada e disfunção ventricular mesmo com trombólise e revascularização precoces. OBJETIVO: Investigar o comportamento das citocinas circulantes em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) e a relação delas com a função ventricular. MÉTODOS: No estudo BATTLE-AMI (Avaliação dos Linfócitos Tipos B e T no Infarto Agudo do Miocárdio), os pacientes com IAMCSST foram tratados com uma estratégia farmacoinvasiva. Os níveis de citocinas (IL-1ß, IL-4, IL-6, IL-10 e IL-18) no plasma foram testados através de ensaio de imunoadsorção enzimática (ELISA) no início do estudo e após 30 dias. A massa infartada e a fração de ejeção ventricular esquerda (FEVE) foram examinadas por ressonância magnética cardíaca 3-T. Valores de p menores que 0,05 foram considerados significativos. RESULTADOS: Na comparação com o início do estudo, níveis mais baixos foram detectados para IL-1ß (p = 0,028) e IL-18 (p < 0,0001) após 30 dias do IAMCSST, enquanto níveis mais altos foram observados para IL-4 (p = 0,001) e IL-10 (p < 0,0001) no mesmo momento. Em contrapartida, nenhuma mudança foi detectada nos níveis de IL-6 (p = 0,63). Os níveis da proteína C-reativa de alta sensibilidade e de IL-6 se correlacionaram no início do estudo (rho = 0,45, p < 0,0001) e 30 dias após o IAMCSST (rho = 0,29, p = 0,009). No início do estudo, a correlação entre os níveis de IL-6 e FEVE também foi observada (rho = -0,50, p = 0,004). CONCLUSÕES: Durante o primeiro mês pós-infarto agudo do miocárdio, observamos uma melhora significativa no balanço das citocinas pró e anti-inflamatórias, exceto da IL-6. Esses achados sugerem risco inflamatório residual. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Alterações precoces nas interleucinas circulantes e no risco inflamatório residual após infarto agudo do miocárdio / Early changes in circulating interleukins and residual inflammatory risk after acute myocardial infarction

Resumo Fundamento: Pacientes com infarto agudo do miocárdio podem apresentar uma grande área infartada e disfunção ventricular mesmo com trombólise e revascularização precoces. Objetivo: Investigar o comportamento das citocinas circulantes em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCSST) e a relação delas com a função ventricular. Métodos: No estudo BATTLE-AMI (Avaliação dos Linfócitos Tipos B e T no Infarto Agudo do Miocárdio), os pacientes com IAMCSST foram tratados com uma estratégia farmacoinvasiva. Os níveis de citocinas (IL-1ß, IL-4, IL-6, IL-10 e IL-18) no plasma foram testados através de ensaio de imunoadsorção enzimática (ELISA) no início do estudo e após 30 dias. A massa infartada e a fração de ejeção ventricular esquerda (FEVE) foram examinadas por ressonância magnética cardíaca 3-T. Valores de p menores que 0,05 foram considerados significativos. Resultados: Na comparação com o início do estudo, níveis mais baixos foram detectados para IL-1ß (p = 0,028) e IL-18 (p < 0,0001) após 30 dias do IAMCSST, enquanto níveis mais altos foram observados para IL-4 (p = 0,001) e IL-10 (p < 0,0001) no mesmo momento. Em contrapartida, nenhuma mudança foi detectada nos níveis de IL-6 (p = 0,63). Os níveis da proteína C-reativa de alta sensibilidade e de IL-6 se correlacionaram no início do estudo (rho = 0,45, p < 0,0001) e 30 dias após o IAMCSST (rho = 0,29, p = 0,009). No início do estudo, a correlação entre os níveis de IL-6 e FEVE também foi observada (rho = -0,50, p = 0,004). Conclusões: Durante o primeiro mês pós-infarto agudo do miocárdio, observamos uma melhora significativa no balanço das citocinas pró e anti-inflamatórias, exceto da IL-6. Esses achados sugerem risco inflamatório residual.

Circulating microparticles and central blood pressure according to antihypertensive strategy.

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Beneficial effects of green banana biomass consumption in patients with pre-diabetes and type 2 diabetes: a randomised controlled trial.

Diabetes mellitus is a global epidemic, characterised as a heterogeneous group of metabolic disorders associated with high risk of CVD. Green banana biomass, which is composed of resistant starches (RS) and cannot be hydrolysed by amylases, delays gastric emptying and modulates insulin sensitivity, thus contributing to improve metabolic disorders. The aim of the present study was to investigate the effects of consumption of RS from green banana biomass on body composition, fasting plasma glucose, glycated Hb (HbA1c) and homeostasis model assessment of insulin resistance in subjects with pre-diabetes or type 2 diabetes on top of treatment. Middle-aged subjects (n 113) of both sexes with pre-diabetes (HbA1c: 5·7-6·4 %) or diabetes (HbA1c ≥ 6·5 %) were randomised to receive nutritional support plus green banana biomass (40 g) (RS: approximately 4·5 g, G1, n 62) or diet alone (G2, n 51) for 24 weeks. Body composition, biochemical analyses and dietary intake were evaluated at the beginning and end of the study. In the experimental group (G1), consumption of RS was associated with reduction in HbA1c (P = 0·0001), fasting glucose (P = 0·021), diastolic blood pressure (P = 0·010), body weight (P = 0·002), BMI (P = 0·006), waist and hip circumferences (P < 0·01), fat mass percentage (P = 0·001) and increase in lean mass percentage (P = 0·011). In controls (G2), reductions were observed in waist and hip circumferences (P < 0·01), HbA1c (P = 0·002) and high-density lipoprotein-cholesterol (P = 0·020). In pre-diabetes or diabetes, non-significant differences were observed in the percentage reduction in HbA1c and fasting glucose in exploratory analyses. Our results indicate that the consumption of bioactive starches is a good dietary strategy to improve metabolic control and body composition.

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Clinical Applications of Point-of-Care Testing in Different Conditions.

BACKGROUND: The use of point-of-care testing (POCT) in different clinical applications is justified by the fact that the time to release the result is shortened, allowing the physician to define the diagnosis and most appropriate therapy in a shorter time. However, the negative aspects must also be highlighted and studied so that we can move forward with the use of these devices. These negative aspects include greater analytical imprecision compared to laboratory automation, the variability between different equipment from different manufacturers, the risk of inappropriate use, a low level of global regulation, higher costs compared with laboratory testing and cost ineffectiveness in terms of health care. Methods and. RESULTS: This review presents some clinical applications of POCT in different scenarios, such as for diabetes mellitus, infectious diseases, pediatrics, and chronic kidney disease, among others. CONCLUSIONS: We hope to see a global consensus on an acceptable quality standard for performing POCT that is adaptable, practical, and cost effective in primary care settings, ensuring patient safety, and minimizing the risk of harm.

Definition of reference ranges for ß-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents.

BACKGROUND: Bone metabolism involves many complex pathways that are disturbed by several bone diseases. The literature shows some limitations concerning pediatric reference intervals to bone markers, mainly because of the low number of patients included in the studies, the heterogeneity of methods, beyond the fact that it is time-consuming and expensive. The aim of this study was to determine reference values for ß-isomerized carboxy-terminal telopeptides collagen type I (ß-CTX), a marker of bone resorption, for children and adolescents. METHODS: Blood samples from 246 patients were collected and ß-CTX was measured using an electrochemiluminescence immunoassay (ECLI). RESULTS AND CONCLUSIONS: We propose reference ranges for ß-CTX concentration from the 2.5 percentile and 97.5 percentile for each age group. The reference values obtained, concerning children and adolescents, might be useful in the evaluation of diseases such as osteosarcoma and anorexia in both childhood as adolescence.

Point-of-Care Testing: General Aspects.

Point-of-Care Testing (POCT) has been highlighted in the health care sector in recent decades. On the other hand, due to its low demand, POCT is at a disadvantage compared to conventional equipment, since its cost is inversely proportional to the volume of use. In addition, for the implementation of POCT to succeed, it is essential to rely on the work of a multidisciplinary team. The awareness of health professionals of the importance of each step is perhaps the critical success factor. The trend towards the continuous advancement of the use of POCT and the great potential of its contributions reinforce the need to implement quality management tools, including performance indicators, to ensure their results. This review presents some advantages and disadvantages concerning POCT and the real need to use it. A worldwide call for the availability of easy-to-use health technologies that are increasingly closer to the final user is one of the main reasons for this focus.

Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.

BACKGROUND: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. METHODS/DESIGN: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events. DISCUSSION: BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.

Monocyte subtypes and the CCR2 chemokine receptor in cardiovascular disease.

Monocytes circulate in the blood and migrate to inflammatory tissues, but their functions can be either detrimental or beneficial, depending on their phenotypes. In humans, classical monocytes are inflammatory cluster of differentiation (CD)14++CD16-CCR2++ cells originated from the bone marrow or spleen reservoirs and comprise ≥92% of monocytes. Intermediate monocytes (CD14++CD16+CCR2+) are involved in the production of anti-inflammatory cytokines [such as interleukin (IL)-10], reactive oxygen species (ROS), and proinflammatory mediators [such as tumor necrosis factor-α (TNF-α) and IL-1ß). Nonclassical monocytes (CD14+CD16++CCR2-) are patrolling cells involved in tissue repair and debris removal from the vasculature. Many studies in both humans and animals have shown the importance of monocyte chemoattractant protein-1 (MCP-1) and its receptor [chemokine receptor of MCP-1 (CCR2)] in pathologies, such as atherosclerosis and myocardial infarction (MI). This review presents the importance of these monocyte subsets in cardiovascular diseases (CVDs), and sheds light on new strategies for the blocking of the MCP-1/CCR2 axis as a therapeutic goal for treating vascular disorders.

Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T types of lymphocytes evaluation in acute myocardial infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial

BACKGROUND: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. METHODS/DESIGN: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months...

Challenges Facing the Use of Endothelial Progenitor Cells in Stem Cell Therapies.

The paper summarizes the difficulties to study the rare population of endothelial progenitor cells in clinical trials, based on the experience of our group in many publications in this area.