Abstract Background Microparticles (MPs) are membrane-derived vesicles released from cells undergoing activation or apoptosis with diverse proinflammatory and prothrombotic activities, that have been implicated in the pathogenesis of systemic sclerosis (SSc). We aimed to evaluate the plasma levels of platelet-derived microparticles (PMPs), endothelial cell-derived microparticles (EMPs), and monocyte-derived microparticles (MMPs) in SSc patients, and the association between MPs and the clinical features of SSc. Methods In this cross-sectional study, 70 patients with SSc and 35 age- and sex-matched healthy controls were evaluated. Clinical and nailfold capillaroscopy (NFC) data were obtained from all patients. Plasma levels of PMPs (CD42+/31+), EMPs (CD105+), and MMPs (CD14+) were quantified by flow cytometry. Results Patients were mainly females (90%), with a mean age of 48.9 years old. PMP, EMP, and MMP levels were significantly increased in SSc patients compared to controls (79.2% ± 17.3% vs. 71.0% ± 19.8%, p = 0.033; 43.5% ± 8.7% vs. 37.8% ± 10.4%, p = 0.004; and 3.5% ± 1.3% vs. 1.1% ± 0.5%, p < 0.0001, respectively). PMP levels were significantly higher in patients with positive anti-topoisomerase-I antibodies (p = 0.030) and in patients with a disease duration > 3 years (p = 0.038). EMP levels were lower in patients with a higher modified Rodnan skin score (p = 0.015), and in those with an avascular score > 1.5 in NFC (p = 0.042). Conclusion The increased levels of PMPs, EMPs and MMPs in scleroderma patients might indicate a possible role for these agents in the pathogenesis of this challenging disease.

Abstract Objective: Amplitude-integrated electroencephalography (aEEG) is a simplified bedside neurophysiology tool that has been implemented in the neonatal intensive care unit and studied in an extensive range of clinical applications in the past decade. This critical review aimed to evaluate a variety of clinical applications of aEEG monitoring in diagnosis, clinical management, and prognosis assessment in critically ill neonates. Sources: The databases of Pubmed, SciELO, Lilacs, and Cochrane, books, and other online resources were consulted, as well as sources of professional experiences. Summary of findings: The clinical use of aEEG to access real-time brain function, background activity, and utility in seizures detection has been described. A critical review was realized considering the authors’ professional experience. Newborns with hypoxic-ischemic encephalopathy and seizures screening represent the most common studied population. However, several studies have shown interesting applications on preterm infants, newborns with congenital heart disease, and other clinical situations of high risk of injury to the developing brain. Conclusion: The aEEG has shown to be a useful non-invasive bedside monitor that aids in evaluating brain function, background activity, and cyclicity. aEEG findings have also demonstrated good prognostic value in a group of critically ill neonates. The aEEG seizure diagnosis capability has limitations, which have been already well established. The use of neonatal brain monitoring such as aEEG was shown to give valuable information in several high-risk clinical situations.

Abstract Objectives: Three-dimensional (3D) cell cultures have many applications such as stem cell biology research, new drug discovery, cancer, and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This disease is characterized by a significant impact on quality of life and productivity. The diversity of factors that act in the progression of CRSwNP point to the creation of a cell culture model that allows the integration of different cell types with extracellular matrix. This work aimed to create a cell culture model in 3 dimensions (spheroids) for the study of Nasal Polyposis. Methods: Nasal polyp tissue from patients diagnosed with CRSwNP was mechanically dissociated using tweezers and a scalpel and the solution containing cells and small aggregates of nasal polyps was transferred to a Petri dish containing 5 mL of culture medium at the concentration of 106 cells/mL. Results: The spheroids were cultivated for 20 days, fixed and analyzed using confocal microscopy. In a 3D culture environment, the spheroids were formed both by clustering cells and from small tissue fragments. In the cultures analyzed, the ciliary beat was present from the dissociation of the cells up to 20 days in culture. Conclusion: Our findings also point to these characteristics showing the environment generated in our study, the cells remained differentiated for a longer time and with ciliary beating. Thus, this work shows that nasal polyp-derived cells can be maintained in a 3D environment, enabling better strategies for understanding CRSwNP in situations similar to those found in vivo. Level of evidence: Laboratory studies.

Resumen Introducción: El trauma es la segunda causa de mortalidad y la sexta de hospitalización en el país, siendo la violencia, los accidentes y las caídas las más prevalentes. Sin embargo, el país está experimentando reflejos de una pandemia de COVID-19, junto a una falta de estudios sobre el trauma, así como sobre la atención clínica. Objetivo: Analizar las características clínicas y epidemiológicas del trauma junto a la violencia, accidentes y caídas entre los años 2019, 2020 y 2021, considerados antes y durante la pandemia COVID-19. Materiales y métodos: Estudio de cohorte retrospectivo, con adultos de 25 a 55 años, que sufrieron trauma relacionado con violencia, caídas y otros accidentes, en el período comprendido entre marzo y junio de 2019, 2020 y 2021, en la ciudad de São Paulo. Las encuestas de datos fueron realizadas por el sistema TABNET, por el Departamento Municipal de Salud. Dentro de este sistema, la búsqueda se realizó a través del Sistema de Información para la Vigilancia de Accidentes, de la Coordinación de Vigilancia en Salud, en el cual las situaciones de violencia fueron notificadas y registradas por el Sistema Nacional de Información de Enfermedades Notificables. Posteriormente, se accedió al Sistema de Información de Vigilancia de Violencia y Accidentes, con enfoque en notificaciones y registro de caídas y otros accidentes. Resultados: El trauma siguió siendo más prevalente para los hombres, con educación primaria completa y raza predominantemente entre blancos y morenos. Al analizar los diferentes tipos de violencia: física, tortura y sexual, hubo mayores porcentajes de prevalencia durante el año 2019, período prepandémico de COVID-19, a excepción de la violencia psicológica / moral, que fue mayor en 2021. Nótese que los diferentes mecanismos de violencia fueron significativamente más prevalentes en 2019, así como las diferentes causas de violencia, caídas y traumatismos automovilísticos que involucran a peatones, ocupantes, conductores y pasajeros. La atención ambulatoria confirmó la tendencia de superioridad en el período prepandémico, sin embargo, la atención hospitalaria de emergencia mostró un mayor número de solicitudes en 2020 y 2021. Conclusión: Los traumas de violencia, accidentes y caídas son más prepandémico en comparación con el período durante la pandemia COVID-19; así como la búsqueda de asistencia sanitaria en hospitales y clínicas. Estos hallazgos muestran una posible reducción en los informes de trauma y una menor demanda de asistencia durante la pandemia.

Abstract Introduction: Trauma is the second leading cause of mortality and the sixth leading cause of hospitalization in the country, with violence, accidents, and falls being the most prevalent. However, the country is experiencing reflexes of the COVID-19 pandemic, together with a lack of studies on trauma, as well as on clinical care. Objective: To analyze the clinical and epidemiological characteristics of trauma related to violence, accidents, and falls among the years 2019, 2020, and 2021, considered as before and during the COVID-19 pandemic. Material and Methods: Retrospective cohort study, with adults aged 25-55 years, who suffered trauma related to violence, falls, and other accidents, in the period between March and June of 2019, 2020, and 2021, in the city of São Paulo. Data surveys were carried out using the TABNET system, of the Municipal Health Department. Within this system, the search was carried out through the Information System for the Surveillance of Accidents, of the Coordination of Health Surveillance, in which situations of violence were notified and recorded by the National Information System for Notifiable Diseases. Subsequently, the Information System for Surveillance of Violence and Accidents was accessed, focusing on notifications and records of falls and other accidents. Results: Trauma remained more prevalent for males, with complete primary education, and ethnicity predominantly between white or brown. When analyzing the different types of violence: physical, torture, and sexual, there was a prevalence of higher percentages during the year 2019, the pre-pandemic period of COVID-19, except for psychological/moral violence, which was higher in 2021. It should also be noted that the different mechanisms of violence were significantly more prevalent in 2019, as well as the different causes of violence, falls, and car trauma involving pedestrians, occupants, drivers, and passengers. Outpatient care confirmed the higher trend in the pre-pandemic period; however, emergency hospital care showed a greater number of requests in 2020 and 2021. Conclusión: Trauma from violence, accidents, and falls was higher pre-pandemic compared to the period during the COVID-19 pandemic; as well as the search for health care in hospitals and outpatient clinics. These findings show a possible reduction in trauma reports and lower demand for assistance during the pandemic.

ABSTRACT SARS-Cov2 has already infected over 482 million people and caused more than 6.1 million deaths. The beginning of the pandemic has led the health authorities of several countries to adopt non-pharmacological preventive measures such as daycare closures. The reopening took place when the country had the highest rates of infection and mortality (mainly due to the gamma variant (P.1) outbreak) and the beginning of the vaccination program. Therefore, we aimed to investigate the prevalence of SARS-CoV2 in daycare after educational activities resumed. The study was conducted in seven childcare facilities. Swab samples from the nasopharynx were collected from children and staff members. The viral RNA was obtained through PureLink RNA extraction kit purification and SARS-CoV2 presence was detected using the All plex SARS-CoV2 kit. The study population included 201 participants, including daycare workers and children. The average age of the workers and children is 40 and 3 years old, respectively. Among the children, 47.5% are female and among the workers, 91.4%. One (0.5%) test came out positive for the presence of SARS-CoV-2, which was from a sample of an asymptomatic childcare worker, and no secondary infections were detected. Considering that the return to daycare activities occurred during a period with a high number of deaths and a lack of vaccines throughout the country, the small number of cases indicates the effectiveness of the several preventive measures used by daycare centers in preventing SARS-CoV2 transmission.

RESUMO Introdução: A diminuição da atividade física tem sido associada à piora da saúde mental e é motivo de preocupação durante a pandemia de COVID-19. Objetivo: Comparar grupos de estudantes de medicina (EM) que praticam diferentes níveis de atividade física moderada e vigorosa (AFMV) durante a pandemia de COVID-19, com relação aos sintomas de ansiedade e depressão (BAI-BDI), qualidade do sono (PSQI), e atividade física (AF) - leve, moderada, vigorosa (AFL, AFM, AFV) e comportamento sedentário (CS). Métodos: Esta pesquisa com desenho transversal avaliou 218 EM. Os dados das características dos EM foram coletados por meio de formulários on-line: AF, CS, BAI, BDI e PSQI. Para as análises estatísticas, utilizou-se odds ratio (OR) para a presença de sintomas elevados de ansiedade e depressão e má qualidade do sono de EM e AFMV. O D de Cohen (tamanho do efeito, TE) e o intervalo de confiança (IC de 95%), teste de Mann-Whitney: baixa MVPA (mediana = 0 minuto) e alta MVPA (Mediana = 390 minutos) foram registrados. Resultados: Encontramos um pequeno TE para sintomas de depressão (TE 0,26; IC de 95%; 0,00-0,53; p = 0,029) e diferenças significativas (p < 0,05) para sintomas de ansiedade (TE 0,17; IC de 95%; 0,09-0,44; p = 0,037). Também houve tendência de significância para o comportamento sedentário nos dias de semana (TE 0,27; IC de 95%; 0,00-0,53; p = 0,051). A OR para MVPA e a presença de sintomas de ansiedade elevada foi de 0,407 (IC de 95% = 0,228-0,724). Conclusões: Os EM que praticavam maior MVPA apresentaram menos sintomas de ansiedade e depressão durante a pandemia de COVID-19. Nível de evidência III; Estudo de caso-controle.

ABSTRACT Introduction: Decreased physical activity has been associated with poorer mental health and is a cause for concern during the COVID-19 pandemic. Objective: To compare groups of medical students (MS) who practiced different levels of moderate and vigorous physical activity (MVPA) during the COVID-19 pandemic, in relation to symptoms of anxiety and depression (BAI-BDI), sleep quality (PSQI), and physical activity (PA) - light, moderate, vigorous (LPA-MPA and VPA), and sedentary behavior (SB). Methods: This research is a cross-sectional study involving 218 MS. Data on the characteristics of the MS were collected through online forms: PA, SB, BAI, BDI, and PSQI. The Cohen's D (Effect Size - ES) and confidence interval (95% CI), Mann-Whitney test: Lower MVPA (Median=0 minute) and Higher MVPA (Median=390 minutes) were recorded. For the statistical analyses, we used: the Odds ratio (OR) for the presence of symptoms of high levels of anxiety and depression and poor sleep quality in the MS and MVPA. Results: We found a small ES for symptoms of depression (ES 0.26 95% CI 0.00 0.53 p=0.029), and significant differences (p<0.05) for symptoms of anxiety (ES 0.17 95% CI −0.09 0.44 p=0.037). There was also a significant tendency for sedentary behavior on weekdays (ES 0.27 95% CI 0.00 0.53 p = 0.051). The OR for MVPA and the presence of symptoms of high levels of anxiety was 0.407 (95% CI = 0.228 to 0.724). Conclusions: the MS who practiced higher MVPA presented less symptoms of anxiety and depression during the COVID-19 pandemic. Level of evidence III; Case-control study.

RESUMEN Introducción: La disminución de la actividad física se ha asociado con un empeoramiento de la salud mental y es motivo de preocupación durante la pandemia de COVID-19. Objetivo: Comparar grupos de estudiantes de medicina (EM) con diferentes momentos de actividad física moderada y vigorosa (AFMV) durante la pandemia COVID-19, en relación a los síntomas de ansiedad y depresión (BAI-BDI), calidad de sueño (PSQI) y actividad física (AF) - comportamiento leve, moderado, vigoroso (LPA-MPA y VPA) y sedentario (SB). Métodos: Esta encuesta transversal evaluó 218 EM. Los datos se recogieron mediante formularios online sobre las características del grupo PA, SB, BAI, BDI y PSQI. D de Cohen (ES) y el intervalo de confianza (IC del 95%), prueba de Mann-Whitney: AFMV baja (mediana = 0 minutos) y AFMV (mediana = 390 minutos); En el análisis estadístico se utilizó la razón de probabilidades (OR) para la presencia de síntomas de ansiedad alta y síntomas depresivos, la mala calidad del sueño de la EM y la MVPA. Resultados: Una pequeña EE para síntomas de depresión (ES 0.26 IC 95% 0.00 0.53 p = 0.029) y diferencias significativas (p <0.05) para síntomas de ansiedad (ES 0.17 IC 95% −0, 09 0.44 p = 0.037). Se verificó tendencia de significancia para el día de la semana SB (ES 0.27 IC 95% 0.00 0.53 p = 0.051). Se verificó la OR para AFMV y la presencia de síntomas de alta ansiedad de 0,407 (IC del 95% = 0,228 a 0,724). Conclusiones: La EM con un AFMV más alto tiene menos síntomas de ansiedad y síntomas de depresión durante la pandemia de COVID-19. Nivel de evidencia III; Estudio de casos y controles.

OBJECTIVES: Although child mortality has declined significantly in recent decades, the reduction of neonatal mortality remains a major challenge as neonatal mortality represents 2/3 of the mortality rate in this population. The objective of this study was to evaluate the utility of the Score for Neonatal Acute Physiology Perinatal Extension II (SNAP-PE II) score for evaluating the survival prognosis of newborns admitted to a neonatal intensive care unit (NICU). METHODS: The study design involved an observational cross-sectional retrospective collection, as well as a prospective component. The sample included all newborns admitted to the NICU validated by the SNAP-PE II tool from January 1 to December 31, 2014. RESULTS: A predominance of young mothers (25.4 years), underwent prenatal care (86.2%), however a considerable percentage (49.4%) of mothers received insufficient medical consultation (less than six consults during their pregnancy). A prevalence of male admissions (62.4%) were noted in the NICU. Premature (61.7%) and underweight (weight <2,500 grams) newborns were also prevalent. The SNAP-PE II score showed an association between the infants who were discharged from the neonatal unit and the non-survivors. An increased prevalence of low birth weight and hypothermia was noted in the group of non-survivors. The mean arterial pressure appears to be a significant risk factor in the newborn group that progressed to death. Hypothermia, mean arterial pressure, and birth weight were the most significant variables associated with death. CONCLUSION: The SNAP-PE II was a beneficial indicator of neonatal mortality. The prevention of prematurity and hypothermia by improving maternity care and newborn care can decisively influence neonatal mortality.

RESUMO Objetivo Verificar se a triagem de urina por fitas reativas é capaz de predizer a cultura de urina. Métodos Estudo retrospectivo realizado entre janeiro e dezembro de 2014 com 8.587 pacientes, com solicitação médica de triagem de urina (fita), sedimento urinário e cultura de urina. Foram analisados sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e curva ROC. Resultados Foram positivas 17,5% das culturas. O nitrito apresentou sensibilidade de 28% e especificidade de 99%. O valor preditivo positivo foi de 89% e o valor preditivo negativo de 87%. Esterase apresentou sensibilidade de 79% e especificidade de 84%. Valor preditivo positivo e valor preditivo negativo foram de 51% e 95%, respectivamente. A combinação de nitrito ou esterase positivos apresentou sensibilidade de 85% e especificidade de 84%. Valor preditivo positivo e valor preditivo negativo foram, respectivamente, 53% e 96%. O sedimento positivo (mais de dez leucócitos por microlitro) apresentou sensibilidade de 92% e especificidade de 71%. O valor preditivo positivo foi 40% e o negativo, 98%. A combinação de nitrito e sedimento urinário positivos apresentou sensibilidade de 82% e especificidade de 99%. Os valores preditivos positivo e negativo foram 91% e 98%, respectivamente. Para o nitrito ou esterase positivos mais os leucócitos positivos, a sensibilidade foi de 94% e a especificidade de 84%. O valor preditivo positivo foi de 58% e o negativo foi de 99%. Com base na curva ROC, o melhor indicador de urocultura positiva foi a associação entre a esterase ou nitrito positivos na fita mais os leucócitos positivos no sedimento, seguido por nitrito e esterase positivos, sedimento urinário positivo isolado, esterase positiva isolada, nitrito positivo isolado e, finalmente, pela associação entre nitrito e sedimento urinário positivos (AUC: 0,845, 0,844, 0,817, 0,814, 0,635 e 0,626, respectivamente). Conclusão Uma urocultura negativa pode ser prevista com resultados negativos na fita. Portanto, este teste pode ser um preditor confiável de urocultura negativa.

ABSTRACT Objective To investigate whether the urine dipstick screening test can be used to predict urine culture results. Methods A retrospective study conducted between January and December 2014 based on data from 8,587 patients with a medical order for urine dipstick test, urine sediment analysis and urine culture. Sensitivity, specificity, positive and negative predictive values were determined and ROC curve analysis was performed. Results The percentage of positive cultures was 17.5%. Nitrite had 28% sensitivity and 99% specificity, with positive and negative predictive values of 89% and 87%, respectively. Leukocyte esterase had 79% sensitivity and 84% specificity, with positive and negative predictive values of 51% and 95%, respectively. The combination of positive nitrite or positive leukocyte esterase tests had 85% sensitivity and 84% specificity, with positive and negative predictive values of 53% and 96%, respectively. Positive urinary sediment (more than ten leukocytes per microliter) had 92% sensitivity and 71% specificity, with positive and negative predictive values of 40% and 98%, respectively. The combination of nitrite positive test and positive urinary sediment had 82% sensitivity and 99% specificity, with positive and negative predictive values of 91% and 98%, respectively. The combination of nitrite or leukocyte esterase positive tests and positive urinary sediment had the highest sensitivity (94%) and specificity (84%), with positive and negative predictive values of 58% and 99%, respectively. Based on ROC curve analysis, the best indicator of positive urine culture was the combination of positives leukocyte esterase or nitrite tests and positive urinary sediment, followed by positives leukocyte and nitrite tests, positive urinary sediment alone, positive leukocyte esterase test alone, positive nitrite test alone and finally association of positives nitrite and urinary sediment (AUC: 0.845, 0.844, 0.817, 0.814, 0.635 and 0.626, respectively). Conclusion A negative urine culture can be predicted by negative dipstick test results. Therefore, this test may be a reliable predictor of negative urine culture.

Resumo Fundamento: Os efeitos da exposição crônica ao exercício sobre biomarcadores vasculares foram pouco estudados. Objetivo: Nosso estudo teve como objetivo comparar as quantidades de células progenitoras endoteliais (CPEs), e de micropartículas endoteliais (MPEs) e plequetárias (MPPs) de corredores profissionais com controles sadios. Métodos: Vinte e cinco corredores de meia maratona e 24 controles pareados quanto à idade e ao sexo foram incluídos no estudo. CPEs (CD34+/KDR+, CD133+/KDR+ e CD34+/CD133+), MPE (CD51+) e MPPs (CD42+/CD31+) foram quantificadas por citometria de fluxo. Todas as amostras de sangue foram obtidas após 12 horas de jejum, e os atletas foram incentivados a realizar seus exercícios de rotina no dia anterior à coleta. Resultados: Em comparação aos controles, CPEs CD34+/KDR+ (p=0,038) e CD133+/KDR+ (p=0,018) estavam aumentados, e CPEs CD34+/CD133+ não foram diferentes (p=0,51) nos atletas. As concentrações de MP não diferiram entre os grupos. Conclusão: A exposição crônica ao exercício em corredores profissionais associou-se a uma maior porcentagem de CPEs. Considerando o número similar de MPs entre atletas e controles, o estudo sugere um efeito favorável do exercício sobre esses biomarcadores vasculares.

Abstract Background: The effects of chronic exposure to exercise training on vascular biomarkers have been poorly explored. Objective: Our study aimed to compare the amounts of endothelial progenitor cells (EPCs), and endothelial (EMP) and platelet (PMP) microparticles between professional runners and healthy controls. Methods: Twenty-five half-marathon runners and 24 age- and gender-matched healthy controls were included in the study. EPCs (CD34+/KDR+, CD133+/KDR+, and CD34+/CD133+), EMP (CD51+) and PMP (CD42+/CD31+) were quantified by flow-cytometry. All blood samples were obtained after 12 h of fasting and the athletes were encouraged to perform their routine exercises on the day before. Results: As compared with controls, the CD34+/KDR+ EPCs (p=0.038) and CD133+/KDR+ EPCs (p=0.018) were increased, whereas CD34+/CD133+ EPCs were not different (p=0.51) in athletes. In addition, there was no difference in MPs levels between the groups. Conclusion: Chronic exposure to exercise in professional runners was associated with higher percentage of EPCs. Taking into account the similar number of MPs in athletes and controls, the study suggests a favorable effect of exercise on these vascular biomarkers.

SUMMARY Cryptococcosis is a leading invasive fungal infection in immunocompromised patients. Considering the high prevalence and severity of these infections in immunocompromised patients attended at HC-FMRP-USP, the present research aimed to characterize the clinical isolates of Cryptococcus strains by biochemical and molecular methods and evaluate antifungal susceptibility of clinical isolates. Fifty isolates from 32 HIV-positive patients were obtained at HC-FMRP-USP. Most of the isolates (78.1%) were identified as C. neoformans, and 100% of C. neoformans and C. gattii strains were susceptible to amphotericin B, ketoconazole and fluconazole. All isolates were classified as serotype A (grubbii variety) by PCR and most of them were characterized in mating type MATa. PCR analysis of specific M13 microsatellite sequence revealed that VNI type was predominant among C. neoformans, while VGII was predominant among C. gattii. The strains did not show a significant resistance to the antifungals tested, and Canavanine-Glycine-Bromthymol Blue Agar (CGB) proved to be a reliable test presenting a good correlation with the molecular characterization. C. neoformans isolated from disseminated infections in the same patient showed molecular identity when different anatomical sites were compared; besides, the studied strains did not present a significant increase in resistance to antifungal agents. In addition, the homogeneity of the molecular types and detection of the mating types suggested a low possibility of crossing among the strains.

A prevenção primária da doença cardiovascular constitui uma opção de grande relevância pelos seus impactos na saúde. Alguns biomarcadores têm sido considerados úteis na avaliação da doença cardiovascular, dentre eles micropartículas originadas de diferentes populações de células. Micropartículas são estruturas liberadas pela membrana de diferentes tipos celulares após ativação ou apoptose, presentes tanto no plasma de indivíduos saudáveis (níveis considerados fisiológicos) quanto em portadores de diferentes doenças. Muitos estudos têm sugerido uma associação entre micropartículas e diferentes condições patológicas, destacando-se a relação com o desenvolvimento das doenças cardiovasculares. Além disso, têm sido descritos os efeitos de diferentes terapias hipolipemiantes na mensuração de micropartículas. Os estudos ainda são controversos quanto aos níveis de micropartículas que possam ser considerados patológicos, e os métodos utilizados ainda são variados, o que sugere a necessidade da padronização dos diferentes protocolos utilizados, visando à utilização de micropartículas como biomarcadores úteis na prática clínica.

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

INTRODUÇÃO: Atorvastatina 80 mg é recomendada a pacientes portadores de doença coronária para redução de eventos cardiovasculares, havendo controvérsia sobre as interações farmacocinéticas entre doses elevadas das estatinas e uso concomitante de clopidogrel, por compartilharem a mesma via de biotransformação. Este estudo avaliou os efeitos da terapia combinada atorvastatina/clopidogrel na farmacocinética da estatina e função plaquetária em pacientes com doença coronária estável, sob uso crônico e efetivo de estatina MÉTODO: Os pacientes foram admitidos quatro vezes para internação (V1 a V4) em leito-dia. Sete dias (D) antes da primeira internação a estatina em uso foi suspensa. A seguir, receberam atorvastatina 80 mg (D1 a D22) e clopidogrel 75 mg/dia (D8 a D29). Em todas as V foram obtidas amostras de sangue em jejum para dosagens lipídicas, avaliação da função plaquetária (técnica da placa e cone) e quantificação dos níveis plasmáticos de atorvastatina (cromatografia líquida e espectrometria de massa) RESULTADOS: A suspensão por uma semana da estatina modificou o perfil lipídico (P < 0,05 vs. basal), ocorrendo rápida melhora de todas as frações lipídicas após atorvastatina 80 mg (P < 0,005; V1 > V2, V3 e V4). A adesão plaquetária foi menor com clopidogrel isolado (P = 0,003; V4 < V1, V2 e V3), enquanto para a agregação houve menor valor com tratamento combinado atorvastatina/clopidogrel ou clopidogrel isolado comparado aos demais períodos (P < 0,0001; V3 e V4 < V1 e V2). O clopidogrel não modificou as concentrações de atorvastatina CONCLUSÃO: Atorvastatina em alta dose não afetou as respostas plaquetárias ao clopidogrel; entretanto, curto período de suspensão da estatina piorou o perfil lipídico e a função plaquetária.

BACKGROUND: Atorvastatin 80 mg is recommended in patients with coronary artery disease to reduce cardiovascular events, however, there is controversy regarding the pharmacokinetic interactions between high doses of statins and the concomitant use of clopidogrel, since they share the same biotransformation pathway. This study evaluated the effects of the atorvastatin/clopidogrel combination therapy on the pharmacokinetics of statins and on platelet function of patients with stable coronary artery disease receiving chronic statins METHOD: Patients were admitted four times (V1 to V4) to a day-clinic. Statin was discontinued seven days (D) before the first admission. Patients then received atorvastatin 80 mg (D1 to D22) and clopidogrel 75 mg/day (D8 to D29). Fasting blood samples were obtained at all time points for lipid measurements, platelet function tests (cone and plate technique), and quantification of atorvastatin plasma levels (liquid chromatography and mass spectrometry) RESULTS: The discontinuation of statins for one week changed the lipid profile (P < 0.05 vs. baseline), with an early improvement of all lipid parameters after the administration of atorvastatin 80 mg (P < 0.005; V1 > V2, V3 and V4). Platelet adhesion was lower with clopidogrel alone (P = 0.003; V4 < V1, V2 and V3), whereas platelet aggregation values were lower following the atorvastatin/clopidogrel combination therapy or clopidogrel alone when compared to the other time points (P < 0.0001; V3 and V4 < V1 and V2). The use of clopidogrel did not affect atorvastatin serum levels CONCLUSION: High-dose atorvastatin did not affect platelet responses to clopidogrel, however the short-term statin discontinuation worsened the lipid profile and platelet function.