Combination of granulocyte-monocyte apheresis and tofacitinib: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. PATIENTS AND METHODS: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. CONCLUSION: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.

Obesidad y monocitos macrófagos en el tejido adiposo / Adipose tissue monocytes and macrophages in obesity

Introducción: el tejido adiposo ha sido objeto de estudio en las últimas décadas y existen nuevos conceptos de su compleja biología. Se conoce que la obesidad está asociada con un estado inflamatorio crónico de bajo grado tanto local como sistémico y parece desempeñar un papel clave en las consecuencias del aumento en diferentes comorbilidades metabólicas y vasculares. Discusión: de los diversos tipos de células inmunes que contribuyen a la inflamación inducida por la obesidad, los monocitos/macrófagos en el tejido adiposo juegan un papel central. Las modificaciones estructurales y fenotípicas de ambas células pueden contribuir no solo a alteraciones inflamatorias y metabólicas, sino también ayudar a mantener la homeostasis del tejido adiposo en respuesta al aumento de la grasa corporal. Los macrófagos son células efectoras esenciales en la organización de la inflamación, ya que se cree que promueven la progresión de la obesidad y los trastornos relacionados. No está completamente establecido si dichas células ejercen un papel beneficioso o nocivo en el tejido adiposo. En cualquier caso, su presencia modifica la biología de las células adiposas especializadas. Conclusiones: en esta revisión se analiza el conocimiento sobre la contribución de los monocitos/macrófagos dentro del tejido adiposo en el desarrollo y mantenimiento de la obesidad y las complicaciones potenciales relacionadas.

Utilizing the lymphocyte-monocyte ratio in predicting the recurrence of spontaneous pneumothorax.

OBJECTIVE: Lymphocyte-to-monocyte ratio (LMR) has been introduced as a predictor and a prognostic factor for multiple diseases. This study aimed to determine the efficiency of LMR in predicting the recurrence of spontaneous pneumothorax. MATERIALS AND METHODS: A total of 374 patients who had received chest tubes at the first episode of primary spontaneous pneumothorax were examined in terms of age, gender, side of the pneumothorax, status of recurrence, LMRs at the time of admittance and recurrence, and the interval until the recurrence. RESULTS: Recurrence was diagnosed in 106 (28.3%) patients, whereas the mean time until the recurrence was 15.32 ± 5.57 months. Significantly, the recurrence rate was higher, while the time until the relapse was shorter for patients with elevated levels of LMR. Moreover, LMR counting over 1.25 demonstrated a 70.8% sensitivity and a 94.4% specificity in predicting a potential recurrence. CONCLUSIONS: Calculation of LMR at the first episode of spontaneous pneumothorax contributes to predict a potential recurrence when combined with traditional risk factors.

OBJETIVOS: La proporción de linfocitos a monocitos (PLM) se ha introducido como un predictor y un factor pronóstico para múltiples enfermedades. Este estudio tuvo como objetivo determinar la eficiencia de LMR en la predicción de la recurrencia del neumotórax espontáneo. MATERIALES Y MÉTODOS: Un total de 374 pacientes que habían recibido tubos de tórax en el primer episodio de neumotórax espontáneo primario fueron examinados en términos de edad, género, lado del neumotórax, estado de recurrencia, PLM al momento del ingreso y recurrencia, y el intervalo hasta la recurrencia. RESULTADOS: Se diagnosticó recidiva en 106 (28.3%) pacientes, siendo el tiempo medio hasta la recidiva de 15.32 ± 5.57 meses. Significativamente, la tasa de recurrencia fue mayor, mientras que el tiempo hasta la recaída fue más corto para los pacientes con niveles elevados de PLM. Además, el recuento de PLM superior a 1.25 demostró una sensibilidad del 70.8 % y una especificidad del 94.4 % para predecir una posible recurrencia. CONCLUSIÓN: Calcular la PLM en el primer episodio de neumotórax espontáneo predice una posible recurrencia cuando se combina con los factores de riesgo tradicionales.

Increased monocytes are associated with overweight in children and adolescents with autism spectrum disorder / El aumento de los monocitos se asocia con el sobrepeso en los niños y adolescentes con trastorno del espectro autista

Objective: to investigate the monocyte count and its association with nutritional status in children and adolescents with autism spectrum disorder (ASD). Methods: a cross-sectional study carried out at a Neurodevelopmental Center in the south of Brazil, with 68 ASD patients aged 3 to 18 years. The number of monocytes (per mm3) was determined in blood samples. Nutritional status was defined as BMI-for-age according to WHO standards. The Children's Eating Behaviour Questionnaire and a standard questionnaire to collect sociodemographic and clinical characteristics were administered to caregivers. Comparisons between sociodemographic, clinical, and eating behavior variables were performed with parametric tests. Linear regression was used to test the association between nutritional status and monocyte count. Results: mean age was 8.6 ± 3.3 years, 79 % were males and 66 % were overweight. In the unadjusted regression overweight was associated with higher monocyte counts compared to those non-overweight (B: 64.0; 95 % CI, 13.9 to 114.1; β: 0.30, p = 0.01). This association remained significant after adjustment for the subscale of “emotional overeating” (B: 37.0; 95 % CI, 17.1 to 91.3; β: 0.29; p = 0.02). The variability in monocyte count attributed to overweight was 14 %. Conclusions: overweight is associated with a higher monocyte count in children and adolescents with ASD. Nutritional intervention to control overweight is essential to mitigate the negative impact on inflammatory activity and immune dysfunction in these patients. (AU)

Objetivo: investigar el recuento de monocitos y su asociación con el estado nutricional en niños y adolescentes con trastorno del espectro autista (TEA). Método: estudio transversal realizado en el Centro de Neurodesarrollo, en el sur de Brasil, con 68 pacientes con TEA de 3 a 18 años de edad. Se determinó el número de monocitos (por mm3) en muestras de sangre. El estado nutricional se definió como IMC para la edad según los estándares de la OMS. Se aplicó a los cuidadores el Cuestionario de Conducta Alimentaria Infantil y un cuestionario estándar para recoger características sociodemográficas y clínicas. Las comparaciones entre las variables sociodemográficas, clínicas y de conducta alimentaria se realizaron con pruebas paramétricas. Se utilizó la regresión lineal para probar la asociación entre el estado nutricional y el recuento de monocitos. Resultados: la edad media fue de 8,6 ± 3,3 años, el 79 % eran varones y el 66 % tenían sobrepeso. En la regresión no ajustada, el sobrepeso se asoció a un mayor número de monocitos en comparación con los que no tenían sobrepeso (B: 64,0; IC 95 %: 13,9 a 114,1; β: 0,30; p = 0,01). Esta asociación siguió siendo significativa tras ajustar la subescala de “sobrealimentación emocional” (B: 37,0; IC 95 %: 17,1 a 91,3; β: 0,29; p = 0,02). La variabilidad en el recuento de monocitos atribuida al sobrepeso fue del 14 %. Conclusiones: el sobrepeso se asocia a un mayor recuento de monocitos en niños y adolescentes con TEA. La intervención nutricional para controlar el sobrepeso es esencial para mitigar el impacto negativo sobre la actividad inflamatoria y la disfunción inmune en estos pacientes. (AU)

Monocyte distribution width (MDW) as an infection indicator in severe patients attending in the Emergency Department: a pilot study / Ancho de distribución de los monocitos como indicador de infección en pacientes graves atendidos en Urgencias: estudio piloto

Background. The aim of the present study was to evaluate the diagnostic performance of monocyte distribution width (MDW) as a biomarker for sepsis diagnosis in severe patients attended in the Emergency Department for different conditions and not only infections. Methods. We performed an observational study in a consecutive prospective cohort including severe patients attending the Emergency Department with different conditions. MDW and other biomarkers were determined from samples obtained during the first care of patients. The diagnostic performance of the different biomarkers was determined based on the final diagnosis at patient discharge. Results: One hundred two patients, with a mean age of 76.7 (SD 16.5) years were included, 53 being (51.9%) male. Among the patients included, 65 (63.7%) had an infectious disease while the remaining had other different conditions. A MDW cut-off of 20.115 provided the best accuracy to identify infected patients, with a sensitivity of 89.2 (95% CI 79.4-94.7), a specificity of 89.2 (95% CI 75.3-95.7), a positive predictive value of 93.5 (95% CI 84.6-97.5), a negative predictive value of 82.5% (95% CI 68.0-91.3), a positive likelihood ratio of 8.25 (3.26-20.91), and a negative likelihood ratio of 0.12 (0.06-0.24). The area under the receiver operating characteristic curve for infection according to MDW was 0.943 (95% CI 0.897-0.989; p<0.001). Conclusions: A MDW > 20.115 may be associated with infection and could help to distinguish between infected and non-infected patients in severe patients. These results must be confirmed in new studies due to the limited patient sample included. (AU)

Introducción: El objetivo del presente estudio fue evaluar el desempeño diagnóstico del ancho de distribución de monocitos (MDW) como biomarcador para el diagnóstico desepsis entre pacientes graves atendidos en el servicio de urgencias por diferentes afecciones y no solo por infecciones. Métodos: Realizamos un estudio observacional en una cohorte prospectiva consecutiva que incluyó pacientes graves desde el punto de vista clínico que acudían a urgencias con diferentes patologías. El MDW y otros biomarcadores se determinaron a partir de muestras obtenidas durante la primera atención de los pacientes. Se estudio la precisión de los diferentes biomarcadores para apoyar el diagnósticode infección, basándonos en el diagnóstico final al alta del paciente. Resultados: Se incluyeron 102 pacientes, con una edad media de 76,7 (DE 16,5) años, siendo 53 (51,9%) del sexo masculino. Entre los pacientes incluidos, 65 (63,7%) pacientes tenían una enfermedad infecciosa y el resto otras condiciones diferentes. Un punto de corte MDW de 20,115proporcionó la mejor precisión para identificar pacientes infectados, con un sensibilidad de 89,2 (IC 95 % 79,4-94,7), una especificidad de 89,2 (IC 95 % 75,3-95,7), un valor predictivo positivo de 93,5 (IC 95 % 84,6-97,5), un valor predictivo negativo de 82,5% (IC 95% 68,0-91,3), un coeficiente de probabilidad positivo de 8,25 (3,26-20,91), y uncoeficiente de probabilidad negativo de 0,12 (0,06-0,24). El área bajo la curva característica operativa del receptor para la infección del MDW fue de 0,943 (IC del 95 %: 0,897-0,989; p<0,001). Conclusiones: Un MDW > 20.115 se asocia a padecer una enfermedad infecciosa en un paciente grave y podría ayudar a distinguir entre pacientes infectados y no infectados. Estos resultados deben ser confirmados en nuevos estudios debido a la muestra limitada de pacientes incluidos. (AU)

Increased monocytes are associated with overweight in children and adolescents with autism spectrum disorder.

Introduction: Objective: to investigate the monocyte count and its association with nutritional status in children and adolescents with autism spectrum disorder (ASD). Methods: a cross-sectional study carried out at a Neurodevelopmental Center in the south of Brazil, with 68 ASD patients aged 3 to 18 years. The number of monocytes (per mm3) was determined in blood samples. Nutritional status was defined as BMI-for-age according to WHO standards. The Children's Eating Behaviour Questionnaire and a standard questionnaire to collect sociodemographic and clinical characteristics were administered to caregivers. Comparisons between sociodemographic, clinical, and eating behavior variables were performed with parametric tests. Linear regression was used to test the association between nutritional status and monocyte count. Results: mean age was 8.6 ± 3.3 years, 79 % were males and 66 % were overweight. In the unadjusted regression overweight was associated with higher monocyte counts compared to those non-overweight (B: 64.0; 95 % CI, 13.9 to 114.1; ß: 0.30, p = 0.01). This association remained significant after adjustment for the subscale of "emotional overeating" (B: 37.0; 95 % CI, 17.1 to 91.3; ß: 0.29; p = 0.02). The variability in monocyte count attributed to overweight was 14 %. Conclusions: overweight is associated with a higher monocyte count in children and adolescents with ASD. Nutritional intervention to control overweight is essential to mitigate the negative impact on inflammatory activity and immune dysfunction in these patients.

Introducción: Objetivo: investigar el recuento de monocitos y su asociación con el estado nutricional en niños y adolescentes con trastorno del espectro autista (TEA). Método: estudio transversal realizado en el Centro de Neurodesarrollo, en el sur de Brasil, con 68 pacientes con TEA de 3 a 18 años de edad. Se determinó el número de monocitos (por mm3) en muestras de sangre. El estado nutricional se definió como IMC para la edad según los estándares de la OMS. Se aplicó a los cuidadores el Cuestionario de Conducta Alimentaria Infantil y un cuestionario estándar para recoger características sociodemográficas y clínicas. Las comparaciones entre las variables sociodemográficas, clínicas y de conducta alimentaria se realizaron con pruebas paramétricas. Se utilizó la regresión lineal para probar la asociación entre el estado nutricional y el recuento de monocitos. Resultados: la edad media fue de 8,6 ± 3,3 años, el 79 % eran varones y el 66 % tenían sobrepeso. En la regresión no ajustada, el sobrepeso se asoció a un mayor número de monocitos en comparación con los que no tenían sobrepeso (B: 64,0; IC 95 %: 13,9 a 114,1; ß: 0,30; p = 0,01). Esta asociación siguió siendo significativa tras ajustar la subescala de "sobrealimentación emocional" (B: 37,0; IC 95 %: 17,1 a 91,3; ß: 0,29; p = 0,02). La variabilidad en el recuento de monocitos atribuida al sobrepeso fue del 14 %. Conclusiones: el sobrepeso se asocia a un mayor recuento de monocitos en niños y adolescentes con TEA. La intervención nutricional para controlar el sobrepeso es esencial para mitigar el impacto negativo sobre la actividad inflamatoria y la disfunción inmune en estos pacientes.

Reprogramação metabólica e de função do macrófago por crotoxina

Macrophages (MØ) are cells with high plasticity that can be reprogrammed into two distinct phenotypes – MØ M1 (pro-inflammatory) and MØ M2 (pro-resolving) – according to the nature of the disorder detected in the organism. Experimentally, it is already possible to induce the reprogramming of macrophages to M1 and M2 and the functional and metabolic status of both phenotypes have already been characterized. Previous studies by our group have shown that Crotoxin (CTX) exerts two actions on macrophages that make them suitable in cell therapy: 1) it alters their metabolic and functional profile and 2) these effects are long-lasting. Such effects are observed after a single, short exposure to the toxin. In this context, this research sought to characterize the metabolism and functional status of MØ treated with different concentrations of CTX, with the aim of verifying whether in each concentration it is possible to identify different phenotypes and activation states of the already identified M1 and M2 profiles, in order to seek to reprogram these cells according to specific pathophysiological processes. The capacity for phenotypic reprogramming of monocytes induced by CTX was evaluated in in vitro assays, using cells of the human monocytic lineage (THP-1), previously incubated with RPMI medium (control), or LPS (1ug/mL) or tumor conditioned medium of MCF7 cells (MCT) for 48 hours. Subsequently, they were incubated in the absence (control) or presence of CTX at different concentrations (2 nM; 10 nM; 50 nM and 100 nM) for 1 hour. After the different incubation protocols with the toxin, the differentiation and phenotype markers were analyzed using the qPCR technique, and the latter were also analyzed using flow cytometry. To evaluate the effects of treatments on cellular functions, the phagocytosis capacity, the generation of reactive oxygen species (H2O2) and the production of cytokines by MØ were observed. Cellular metabolism was evaluated through gene expression and activity of key enzymes of the glycolytic pathway. The data presented show that THP-1 cells are satisfactorily differentiated by LPS (1 µg/mL) and tumor environment-MCT (vol. obtained from 1x106 /mL) and these cells have their functions modulated distinctly by CTX, depending on the concentration used. CTX had a dual action on the functions of these human macrophages, since it induced phagocytosis activity, while at the same time stimulated the production of H2O2 in control cells. However, these effects vary depending on the microenvironment stimuli, since, in a tumor and inflammatory context, phagocytosis was preserved in a concentration-dependent manner, concomitant with the increase in H2O2 release in some concentrations. Regarding the metabolic pathways, the undifferentiated THP-1 cells did not show alteration in the gene expression of any of the evaluated glycolytic enzymes, under the effect of any concentration of CTX, suggesting that the toxin does not modulate the expression of these enzymes in the THP-1 cell in monocyte condition. However, when stimulated by LPS and MCT, CTX modulated the gene expression of some enzymes: the 50 nM concentration increased the expression of enzymes from metabolic pathways that are more active in M1 (PFK, FAS and citrate synthase) and also reduced the activity of the enzyme CPT-1 (lipolysis), wich hight activity is related to M2. These effects were accompanied by an increase in pro-inflammatory cytokines. In the inflammatory environment (LPS) the concentration of 10 nM of the toxin promoted a concomitant positive marking of both M1 and M2 markers. Also, at 100 nM CTX promoted parallel release of pro- and anti-inflammatory cytokines. Taken together, the results allow us to state that CTX modulates functions and bioenergetic pathways of human macrophages, depending on the concentration used and the microenvironment stimulus involved.

Os macrófagos (MØ) são células com alta plasticidade que podem ser reprogramados em dois fenótipos distintos – MØ M1 (pró-inflamatórios) e MØ M2 (pró-resolutivos) – de acordo com a natureza do distúrbio detectado no organismo. Experimentalmente, já é possível induzir a reprogramação de macrófagos a M1 e M2 e o estado funcional e metabólico de ambos os fenótipos já foram caracterizados. Estudos prévios de nosso grupo demostraram que a Crotoxina (CTX) exerce em macrófagos duas ações que os tornam aplicáveis em terapia celular: 1) altera seu perfil metabólico e funcional e 2) estes efeitos são de longa duração. Tais efeitos são observados após uma única e curta exposição à toxina. Neste contexto, esta pesquisa buscou caracterizar o metabolismo e o estado funcional de MØ tratados com diferentes concentrações de CTX, com o objetivo de verificar se em cada concentração é possível identificar fenótipos distintos e intermediários aos perfis M1 e M2 já descritos, para assim buscar reprogramar essas células de acordo com processos fisiopatológicos específicos. A capacidade de reprogramação fenotípica de monócitos induzida pela CTX foi avaliada em ensaios in vitro, utilizando células da linhagem monocítica humana (THP-1), incubadas previamente com meio RPMI (controle), ou LPS (1ug/mL) ou meio condicionado tumoral de MCF-7 (MCT) por 48 horas. Posteriormente, elas foram incubadas na ausência (controle) ou presença de CTX em diferentes concentrações (2 nM; 10 nM; 50 nM e 100 nM) ao longo de 1 hora. Após os diferentes protocolos de incubação com a toxina foram analisados os marcadores de diferenciação e de fenótipos, por meio da técnica de qPCR, sendo que os últimos também foram analisados por meio de citometria de fluxo. Para avaliar os efeitos dos tratamentos sobre as funções celulares, foram analisadas a capacidade de fagocitose, a geração de espécies reativas de oxigênio (H2O2) e a produção de citocinas pelos MØ. O metabolismo celular foi avaliado por meio da expressão gênica e atividade das enzimas chave da via glicolítica. Os dados apresentados evidenciam que células THP-1 são satisfatoriamente diferenciadas por LPS (1 µg/mL) e meio condicionado tumoral-MCT (Vol. obtido de 1x106 /mL) e essas células têm suas funções moduladas distintamente pela CTX, a depender da concentração utilizada. A CTX acarretou ação dual sobre as funções destes macrófagos humanos, uma vez que induziu inibição da atividade de fagocitose, ao mesmo tempo que estimulou a produção de H2O2 em células controle. Porém, esses efeitos mudam dependendo dos estímulos do microambiente, já que, em contexto tumoral e inflamatório a fagocitose foi preservada de modo concentração-dependente, acompanhada do aumento da liberação de H2O2 em algumas concentrações. Em relação às vias metabólicas, as células THP-1 não diferenciadas não apresentaram alteração na expressão gênica de nenhuma das enzimas glicolíticas avaliadas, sob o efeito de quaisquer concentrações da CTX, sugerindo que a toxina não modula a expressão dessas enzimas na célula THP-1 na condição de monócito. Porém, quando estimuladas por LPS e MCT a CTX modulou a expressão gênica de algumas enzimas: a concentração de 50 nM aumentou a expressão de enzimas de vias metabólicas que estão mais ativas em M1 (PFK, FAS e citrato sintase) e ainda reduziu a atividade da enzima CPT-1 (lipólise), cuja alta atividade está relacionada ao perfil M2. Estes efeitos foram acompanhados do aumento de citocinas pró-inflamatórias. No ambiente inflamatório (LPS) a concentração de 10 nM da toxina promoveu a marcação positiva concomitante de marcadores tanto de M1 quanto de M2. Já em 100 nM a CTX promoveu liberação paralela de citocinas pró- e anti-inflamatórias. Reunidos, os resultados nos permitem afirmar que a CTX modula funções e as vias bioenergéticas de macrófagos humanos, dependendo da concentração utilizada e do estímulo de microambiente envolvido.

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

Introduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection (AU)

Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção

Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, Brazil / Alterações morfológicas em leucócitos de pacientes com infecção aguda por SARS-CoV-2, Amazônia, Brasil

RESUMO: Introdução: A pandemia pelo novo coronavírus (SARS-CoV-2) trouxe muitas incertezas sobre quais parâmetros laboratoriais seriam mais adequados durante a evolução da COVID 19. Objetivos: Correlacionar os resultados do hemograma (HGM), da relação neutrófilos/linfócitos (R N/L), da proteína C reativa (PCR) e dos achados morfológicos de indivíduos diagnosticados com infecção por SARS-CoV-2 através de Reação em Cadeia da Polimerase em Tempo Real (RT-PCR) em um laboratório particular de Belém, Pará, no período de março a setembro de 2020. Materiais e Métodos: Estudo retrospectivo com 30 indivíduos, de ambos os sexos, qualquer idade e queixa clínica, de origem domiciliar ou hospitalar que realizaram HGM, PCR e RT-PCR para COVID 19 até o 8o dia de infecção. As alterações morfológicas foram analisadas após a seleção das lâminas desses pacientes. Resultados:Amostra composta por 15 homens e 15 mulheres, com idades entre 7 e 92 anos. Desses, 12/30 indivíduos estavam em domicílio e 18/30 internados. As principais queixas foram febre, mal-estar geral, diarreia e desconforto respiratório. O estudo estatístico mostrou a existência de relação de dependência direta entre os aumentos da R N/L, PCR e necessidade de internação (p=0,0005). A análise morfológica mostrou neutrófilos hipossegmentados com granulações tóxicas, monócitos vacuolizados e linfócitos reativos com citoplasma basofílico. Conclusão: Nossos resultados associam os níveis intermediários e elevados da R N/L com o aumento de PCR e a gravidade da doença, porém, sem relação com os achados morfológicos em neutrófilos, linfócitos e monócitos que foram comuns a todos os pacientes diagnosticados até o 8o dia de infecção. (AU)

ABSTRACT: Morphological changes in leukocytes of acute SARS-CoV-2 infection patients, Amazon, BrazilORIGINAL ARTICLEIntroduction: The pandemic for the new coronavirus (SARS-CoV-2) brought many uncertainties about which laboratory parameters would be most suitable during the evolution of COVID 19. Objectives: Correlate the results of the blood count (BC), the neutrophil/lymphocyte ratio (N/LR), the C-reactive protein (CRP) and morphological findings of individuals diagnosed with SARS-CoV-2 infection through Polymerase Chain Reaction in Real Time (RT-PCR) in a private laboratory in Belém, Pará, from March to September 2020. Materials and Methods: Retrospective study with 30 individuals, of both sexes, any age and clinical complaint, of home or hospital origin who underwent BC, CRP and RT-PCR for COVID 19 until the 8th day of infection. Morphological changes were analyzed after selecting the slides for these patients. Results: Sample composed of 15 men and 15 women, aged between 7 and 92 years. Of these 12/30 individuals were at home and 18/30 were hospitalized. The main complaints were fever, malaise, diarrhea and respiratory distress. The statistical study showed a direct dependency relationship between increases in N/LR, CRP and the need for hospitalization (p = 0.0005). Morphological analysis showed hyposegmented neutrophils with toxic granulations, vacuolated monocytes, and reactive lymphocytes with basophilic cytoplasm. Conclusion: Our results associate intermediate and elevated levels of N/LR with increased CRP and disease severity, however, unrelated to the morphological findings in neutrophils, lymphocytes and monocytes that were common to all patients diagnosed up to the 8th day of infection. (AU)

Monocyte chemoattractant protein-1 and hypertension: An overview

Background: The association between hypertension and cardiovascular disease (CVD) has been increasingly studied through early inflammatory biomarkers. The monocyte chemoattractant protein-1 (MCP-1) is the main chemokine implicated in the inflammatory endothelial process, attracting monocytes and macrophages to the atherosclerotic plaque. Methods: We reviewed the main observational studies that have analyzed serum MCP-1 in patients with hypertension regardless of CVD, relating them to target organ damage (TOD). Results: As endothelial dysfunction continues and TOD accumulates, MCP-1 has been perpetuated at higher levels. The relationship between this chemokine and the increase in comorbidities, such as chronic kidney disease, dyslipidaemia, diabetes, and coronary artery disease, became clearer from the observational studies. However, patients with such morbidities use medications with potential anti-inflammatory effects. Conclusion: There is no normal threshold of MCP-1 for the healthy population, nor a uniform curve pattern, due to a balance between genetic factors, age, gender, comorbidities, TOD, and anti-inflammatory effects of drugs. In fact, MCP-1 seems to have a promising role as a tool for further improvement in cardiovascular risk stratification, as prognostic studies have demonstrated an association with fatal and non-fatal cardiovascular outcomes, regardless of other clinical and laboratory predictors.(AU)

Antecedentes: Se ha venido estudiando con mayor frecuencia la asociación entre hipertensión y enfermedad cardiovascular a través de los biomarcadores inflamatorios tempranos. La proteína 1 quimioatrayente de monocitos (MCP-1) es la principal quimioquina implicada en el proceso inflamatorio endotelial, que atrae monocitos y macrófagos a la placa aterosclerótica. Métodos: Revisamos los principales estudios observacionales que han analizado la MCP-1 sérica en pacientes hipotensos independientemente de enfermedad cardiovascular, relacionándolos con el daño del órgano diana. Resultados: A medida que prosigue la disfunción endotelial, y se acumula daño en el órgano diana, MCP-1 se perpetúa a niveles mayores. La relación entre esta quimioquina y el incremento de las comorbilidades, tales como la enfermedad renal crónica, la dislipidemia, la diabetes y la enfermedad arterial coronaria se hizo más evidente a partir de los estudios observacionales. Sin embargo, los pacientes con dichas morbilidades utilizan medicaciones con efectos antiinflamatorios potenciales. Conclusión: No existe un umbral normal de MCP-1 para la población sana, ni un patrón de curva uniforme, debido al equilibrio entre factores genéticos, edad, sexo, comorbilidades, TOD y efectos antiinflamatorios de los fármacos. De hecho, MCP-1 parece tener un rol prometedor como herramienta de mejora futura de la estratificación del riesgo cardiovascular, ya que los estudios pronósticos han demostrado una asociación con los resultados cardiovasculares fatales y no fatales, independientemente de otros factores predictivos clínicos y de laboratorio.(AU)

Monocyte chemoattractant protein-1 and hypertension: An overview.

BACKGROUND: The association between hypertension and cardiovascular disease (CVD) has been increasingly studied through early inflammatory biomarkers. The monocyte chemoattractant protein-1 (MCP-1) is the main chemokine implicated in the inflammatory endothelial process, attracting monocytes and macrophages to the atherosclerotic plaque. METHODS: We reviewed the main observational studies that have analyzed serum MCP-1 in patients with hypertension regardless of CVD, relating them to target organ damage (TOD). RESULTS: As endothelial dysfunction continues and TOD accumulates, MCP-1 has been perpetuated at higher levels. The relationship between this chemokine and the increase in comorbidities, such as chronic kidney disease, dyslipidaemia, diabetes, and coronary artery disease, became clearer from the observational studies. However, patients with such morbidities use medications with potential anti-inflammatory effects. CONCLUSION: There is no normal threshold of MCP-1 for the healthy population, nor a uniform curve pattern, due to a balance between genetic factors, age, gender, comorbidities, TOD, and anti-inflammatory effects of drugs. In fact, MCP-1 seems to have a promising role as a tool for further improvement in cardiovascular risk stratification, as prognostic studies have demonstrated an association with fatal and non-fatal cardiovascular outcomes, regardless of other clinical and laboratory predictors.

A novel activity on thymocytes cells exerted by the rattlesnake (Crotalus durissus cumanensis) venom / Nueva actividad de los timocitos estimulada por el veneno de la serpiente de cascabel (Crotalus durissus cumanensis)

Abstract. Introduction: The thymus is active mainly during the neonatal and pre-adolescent periods. Objective: To test naïve thymocytes proliferation and monocytes stimulation. Materials and methods: We collected fresh thymus tissue from neonate mice after surgery. Suspension cells were coated onto Ficoll-Hypaque support. The obtained cells (thymocytes) were cultured measuring the proliferation of naïve T cells stimulated by Crotalus durissus cumanensis (Cdc) venom at sub-lethal doses (20 ng). Then, we supplemented the wells with AlamarBlue™ and incubated them for 5 h to test their proliferation. Mononuclear cells from mice peripheral blood were collected and layered onto the support of the Ficoll-Hypaque solution. We added the thymocytes actively dividing (25 x 105 cells) from cultures stimulated with Cdc venom at 20 ng/well to cultured monocytes freshly obtained from the Ficoll-Hypaque separation. Both cell populations were incubated for 36 h until monocytes matured to macrophages. Results: The naïve thymocytes rapidly proliferated after stimulation with the Cdc venom (NTCdc) and these successively induced the maturation and function of monocytes progenitor cells to mature macrophages, which ingested Chinese ink. Conclusions: The naïve thymocytes proliferated by stimulation with the Cdc venom and subsequently the NT/Cdc induced the rapid maturation and function of monocytes progenitor cells becoming mature macrophages with their phenotypic characteristics.

Resumen. Introducción. El timo es activo principalmente durante los períodos neonatal y preadolescente. Objetivo. Probar la proliferación de los timocitos tempranos y la estimulación de monocitos que producen. Materiales y métodos. Se recogió tejido de timo fresco después de la cirugía de ratones recién nacidos. La suspensión de células se colocó sobre un soporte de Ficoll-Hypaque. Las células obtenidas (timocitos) se cultivaron y se midió la proliferación de células T vírgenes estimuladas por el veneno de Crotalus durissus cumanensis (Cdc) en dosis subletales (20 ng). A continuación, se agregó AlamarBlue™ a los pocillos y se incubaron durante 5 horas para evaluar la proliferación. Se recogieron células mononucleares de sangre periférica de ratones y se colocaron sobre un soporte de solución de Ficoll-Hypaque. Los timocitos que se dividieron activamente (25 x 105 células) a partir de los cultivos estimulados con veneno de Cdc (20 ng/pocillo) y se agregaron a los cultivos de monocitos recién obtenidos de la separación en la solución de Ficoll-Hypaque. Ambas poblaciones celulares se incubaron durante 36 horas hasta que los monocitos maduraron a macrófagos. Resultados Los timocitos tempranos experimentaron una rápida proliferación estimulada por el veneno de Cdc (NTCdc) y, posteriormente, indujeron la maduración y la función de las células progenitoras de monocitos, los cuales maduraron a macrófagos, que se tiñeron con tinta china. Conclusiones. Los timocitos tempranos proliferaron con la estimulación del veneno de Cdc y, posteriormente, el NT/Cdc indujo la maduración rápida y la función de las células progenitoras de monocitos, transformándose en macrófagos con sus características fenotípicas.

Avaliação da influência dos marcadores inflamatórios na mortalidade de pacientes com AVC isquêmico / Evaluation of the influence of inflammatory markers on the mortality of patients with ischemic stroke

INTRODUÇÃO: À medida que a população envelhece e a expectativa de vida aumenta, a incidência global e a prevalência de AVC isquêmico tendem a aumentar significativamente. Nesse contexto, surge a necessidade de avaliar novos marcadores preditores de mortalidade, como a contagem absoluta de monócitos, relação linfócitos sobre monócitos, relação neutrófilos sobre linfócitos e níveis de proteína C reativa ultrassensível, que além de serem de fácil acesso e baixo custo, sugerem indicar desfecho no paciente com AVC agudo. OBJETIVOS: o objetivo deste estudo foi avaliar a associação dos marcadores inflamatórios com a mortalidade de pacientes com AVC isquêmico. MÉTODOS: trata-se de um estudo retrospectivo observacional a partir de prontuários eletrônicos e exames laboratoriais de pacientes com AVC isquêmico em uma unidade hospitalar de Cascavel/PR. Uma análise estatística descritiva foi conduzida para determinar o perfil dos pacientes segundo o desfecho e aplicado um modelo de regressão logística para verificar as variáveis associadas a mortalidade. Foram considerados significativos apenas os dados com p-valor <0,05. RESULTADOS: Dos 65 pacientes que foram admitidos no estudo, 50 receberam alta hospitalar e 15 foram a óbito no hospital. Entre os marcadores inflamatórios, a relação de neutrófilos sobre linfócitos (OR 1,55; p-valor <0,01) mostrou-se significativamente associada a maior chance de óbito. Os pacientes que faleceram apresentaram níveis superiores de PCR ultrassensível, maior contagem absoluta de monócitos, relação linfócitos sobre monócitos diminuída, e relação neutrófilos sobre linfócitos elevada. CONCLUSÃO: a relação de neutrófilos sobre linfócitos elevada pode estar significativamente associada ao desfecho desfavorável após um AVC isquêmico

IINTRODUCTION: As the population ages and life expectancy increases, the global incidence and prevalence of ischemic stroke tends to rise significantly. In this context, the need arises to evaluate new predictive markers of mortality, such as absolute monocyte count, lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio and C-reactive protein (CRP) levels which, besides being easily accessible and affordable, manage to predict the outcome in patients with acute stroke. OBJECTIVES: the aim of this study was to evaluate the association between inflammatory markers and the mortality in ischemic stroke patients. METHODS: this is a retrospective observational study based on the analysis of electronic medical records and laboratory tests of in-patients who suffered an ischemic stroke in Cascavel/PR. A descriptive statistical analysis was conducted to determine patients´ profile according to the outcome and a logistic regression model was applied in order to verify the variables associated with mortality. Only data with a p-value <0,05 was considered. RESULTS: Out of the 65 patients who suffered an ischemic stroke included in the study, 50 were discharged and 15 died in hospital. Among the inflammatory markers, the neutrophil-tolymphocyte ratio (OR 1.55; p-value <0,01) was associated with a greater chance of death. Patients who died presented with higher levels of ultra-sensitive CRP, higher absolute monocyte count, lower lymphocyte-to-monocyte ratio and higher neutrophil-to- lymphocyte ratio. CONCLUSION: the elevated neutrophil-to-lymphocyte ratio may be significantly associated with negative outcomes following an ischemic stroke

Expressão de Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade (LRP1) em Monócito em Correlação com EIMC em Pacientes Mexicanos Hipertensos / Monocyte Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Expression Correlates with cIMT in Mexican Hypertensive Patients

Resumo Fundamento A hipertensão arterial (HTA) representa um grande fator de risco de morbidade e mortalidade cardiovascular. Ainda não se sabe que mecanismos moleculares específicos estão associados ao desenvolvimento de hipertensão essencial. Objetivo Neste trabalho, analisamos a associação entre expressão mRNA de monócito LRP1, expressão de proteína LRP1, e espessura íntima-média de carótida (EIMC) de pacientes com hipertensão essencial. Métodos A expressão mRNA de monócito LRP1 e os níveis de proteína e EIMC foram quantificados em 200 indivíduos mexicanos, sendo 91 normotensos (NT) e 109 hipertensos (HT) A significância estatística foi definida em p < 0,05. Resultados O grupo de pacientes HT tinha EIMC maior altamente significativa em comparação com os pacientes NT (p = 0,002), e isso está relacionado ao aumento na expressão mRNA de LRP1 (6,54 versus. 2,87) (p = 0,002) e expressão de proteína LRP1 (17,83 versus 6,25), respectivamente (p = 0,001). Essas diferenças foram mantidas mesmo quando dividimos nossos grupos de estudo, levando em consideração apenas aqueles que apresentavam dislipidemia na expressão de mRNA (p = 0,041) e de proteínas (p < 0,001). Também se identificou que a indução de LRP1 mediada por LRP1 em monócitos em de maneira dependente de dose e tempo, com diferença significativa em NT versus HT (0,195 ± 0,09 versus 0,226 ± 0,12, p = 0,046). Conclusão Foi encontrado um aumento em EIMC em indivíduos com hipertensão, associada a expressões de proteína LRP1 e mRNA mais altas em monócitos, independente da presença de dislipidemia em pacientes HT. Esses resultados que a upregulation de LRP1 em monócitos de pacientes hipertensos mexicanos poderia estar envolvida na diminuição da EIMC. (Arq Bras Cardiol. 2021; 116(1):56-65)

Abstract Background Arterial hypertension (HTA) represents a major risk factor for cardiovascular morbidity and mortality. It is not yet known which specific molecular mechanisms are associated with the development of essential hypertension. Objective In this study, we analyzed the association between LRP1 monocyte mRNA expression, LRP1 protein expression, and carotid intima media thickness (cIMT) of patients with essential hypertension. Methods The LRP1 monocyte mRNA expression and protein levels and cIMT were quantified in 200 Mexican subjects, 91 normotensive (NT) and 109 hypertensive (HT). Statistical significance was defined as p < 0.05. Results HT patients group had highly significant greater cIMT as compared to NT patients (p=0.002) and this correlated with an increase in the expression of LRP1 mRNA expression (6.54 vs. 2.87) (p = 0.002) and LRP1 protein expression (17.83 vs. 6.25), respectively (p = 0.001). These differences were maintained even when we divided our study groups, taking into account only those who presented dyslipidemia in both, mRNA (p = 0.041) and proteins expression (p < 0.001). It was also found that Ang II mediated LRP1 induction on monocytes in a dose and time dependent manner with significant difference in NT vs. HT (0.195 ± 0.09 vs. 0.226 ± 0.12, p = 0.046). Conclusion An increase in cIMT was found in subjects with hypertension, associated with higher mRNA and LRP1 protein expressions in monocytes, irrespective of the presence of dyslipidemias in HT patients. These results suggest that LRP1 upregulation in monocytes from Mexican hypertensive patients could be involved in the increased cIMT. (Arq Bras Cardiol. 2021; 116(1):56-65)

Assessment of the hemogram parameters in patients with paroxysmal supraventricular tachycardia: a retrospective study

SUMMARY OBJECTIVE: Inflammation has been suggested as a potential mechanism in the pathogenesis of arrhythmia. Hemogram parameters such as monocyte count to high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have been considered to be markers of inflammation and new cardiovascular risk predictors. This retrospective study aimed to investigate the relationship between MHR, NLR, and MLR in patients with paroxysmal supraventricular tachycardia (PSVT). METHODS: A retrospective study conducted at a university hospital in Bolu, Turkey, between 2017 and 2019. Our study included 196 patients who underwent electrophysiological study (EPS) due to palpitation or documented PSVT on electrocardiography (ECG). Patients having documented atrioventricular nodal re-entrant tachycardia (AVNRT) on ECG or inducible AVNRT on EPS were included in the PSVT group (n=130), and patients with palpitation but without inducible arrhythmia on EPS (n=66) were included in the control group. Routine biochemical and hemogram tests were performed before the EPS procedure. RESULTS: When hemogram parameters were compared, there was no statistically significant difference in MHR values [0.010 (0.001-0.030) vs 0.010 (0.001-0.020) p =0.67]. Additionally, both NLR [2.21(0.74-11.36) vs 1.98(0.72-24.87) p=0.13] and MLR [0.25 (0.03-1.05) vs 0.24(0.07-1.39) p=0.41] were not statistically significant between the two groups. CONCLUSION: There is no significant difference in PSVT patients regarding hemogram parameters including white blood cell subtypes, MLR, NLR, and MHR. Therefore the evaluation of hemogram parameters may not be clinically relevant for PSVT patients.

RESUMO OBJETIVO: A inflamação tem sido sugerida como um mecanismo potencial na patogênese da arritmia. Parâmetros do hemograma, como contagem de monócitos e razão de colesterol lipoproteína de alta densidade (MHP), proporção de neutrófilos / linfócitos (NLP) e proporção de monócitos / linfócitos (MLR), foram considerados marcadores de inflamação e novos preditores de risco cardiovascular. Este estudo retrospectivo teve como objetivo investigar a relação entre MHP, NLP e MLP em pacientes com taquicardia paroxística supraventricular (PSVT). MÉTODOS: Estudo retrospectivo realizado em um hospital universitário em Bolu, Turquia, entre 2017 e 2019. Nosso estudo incluiu 196 pacientes submetidos a estudo eletrofisiológico (EPS) devido a palpitações ou PSVT documentada na eletrocardiografia (ECG). Os pacientes com taquicardia nodal atrioventricular reentrante (AVNRT) no ECG ou AVNRT indutível no EPS foram incluídos no grupo PSVT (n = 130) e os pacientes com palpitações sem arritmia induzível no EPS (n = 66) foram incluídos no grupo controle. Testes bioquímicos e de hemograma de rotina foram realizados antes do procedimento de EPS. RESULTADOS: Quando os parâmetros do hemograma foram comparados, não houve diferença estatisticamente significante nos valores de MHP (0,010 (0,001-0,030) vs 0,010 (0,001-0,020) p = 0,67). Além disso, tanto o NLP (2,21 (0,74-11,36) vs 1,98 (0,72-24,87) p = 0,13) quanto o MLP (0,25 (0,03-1,05) vs 0,24 (0,07-1,39) p = 0,41) não foram estatisticamente significantes entre os dois grupos. CONCLUSÃO: Não há diferença significativa nos pacientes com PSVT em relação aos parâmetros do hemograma, incluindo os subtipos de glóbulos brancos, MHP, NLP e MHP. Portanto, a avaliação dos parâmetros do hemograma pode não ser clinicamente relevante para pacientes com PSVT.

Caracterización biológica de cepas del virus Encefalitis San Luis en células de la inmunidad innata / Biological characterization of St. Louis Encephalitis virus strains in cells of innate immunity

Los flavivirus transmitidos por mosquitos son una amenaza actual y emergente en todo el mundo. Dentro de este género, el virus Encefalitis San Luis (VESL) causa una forma severa de enfermedad neuroinvasiva donde la respuesta inmune es un componente crucial de la defensa del huésped. En este trabajo se investigó la interacción entre VESL y células de la inmunidad innata, en un modelo de infección in vitro de monocitos humanos (células U937) con cepas de distinta virulencia y condiciones epidemiológicas de aislamiento (CbaAr-4005 y 78V-6507). Se evaluó la capacidad de infectar y replicar del virus, como también el efecto citopático y la cinética de viabilidad de monocitos durante la infección. Los resultados demostraron la susceptibilidad de los monocitos a la infección, replicación y muerte por ambas cepas virales. Sin embargo, se hallaron diferencias significativas entre ellas. La cepa epidémica y de mayor virulencia CbaAr-4005 registró una tasa de infección y replicación superior a la de la cepa endémica y de menor virulencia 78V-6507. Se comprobó también que el VESL indujo la muerte de monocitos humanos, dependiendo del tiempo post-infección (pi) y de la cepa. Así, CbaAr-4005 provocó a partir del día 3 pi el doble de mortalidad celular que 78V-6507. Además, en los monocitos infectados se observaron alteraciones de parámetros morfológicos que podrían relacionarse con el tipo de mecanismo de muerte celular asociado a la infección por VESL.

Mosquitoes borne Flavivirus infections are an actual and emergent worldwide threat to human health. Within this genus, Saint Louis Encephalitis Virus (SLEV) causes a severe neuroinvasive disease where immune response is crucial for host survival. In this study the interaction between SLEV and innate immune cells was evaluated. An in vitro infection model with human monocytes (U937 cells) and strains with variations in virulence and isolation conditions (CbaAr-4005 and 78V-6507) were used. Infection capacity, replication capacity, cytopathic effect and monocyte viability kinetics were measured. The results showed susceptibility to infection and replication to both strains. However, significant differences were found among them. CbaAr-4005, the epidemic and more virulent strain, showed higher infection and replication ratios compared to 78V-6507. SLEV infection that induces cell death of human monocytes was also found in a post-infection time and in a strain dependent manner. Since day 3 post-infection, twice the mortality in CbaAr-4005 infected cells was observed. Furthermore, infected monocytes showed alterations in morphologic parameters that could be related with apoptosis mechanisms associated to SLEV infections.

Os Flavivírus transmitidos por mosquitos são uma ameaça atual e emergente no mundo todo. Nesse gênero, o vírus Encefalite Saint Louis (VESL) causa uma forma grave de doença neuroinvasiva onde a resposta imune é um componente crucial da defesa do hospedeiro. Neste trabalho nos investigamos a interação entre VESL e células de imunidade inata em um modelo de infecção in vitro de monócitos humanos (células U937) com estirpe de diferentes virulências e condições epidemiológicas de isolamento (CbaAr-4005 e 78V-6507). Foi avaliada a capacidade do vírus de infectar e replicar , assim como o efeito citopático e a viabilidade cinética dos monócitos durante a infecção. Os resultados demonstraram a suscetibilidade dos monócitos à infecção, replicação e morte por ambas as estirpes virais. No entanto, foram detectadas diferenças significativas entre eles. A estirpe epidémica e de maior virulenta CbaAr-4005 teve uma maior taxa de infecção e replicação do que a estirpe endémica e menos virulenta 78V-6507. Foi comprovado também que o VESL induziu a morte de monócitos humanos, dependendo do tempo pós-infecção (pi) e da estirpe. Assim, a CbaAr-4005 causou a partir do dia 3 pi o dobro da mortalidade celular o que a 78V- 6507. Além disso, alterações nos parâmetros morfológicos foram observadas nos monócitos infectados que poderiam estar relacionadas ao tipo de mecanismo de morte celular associado à infecção pelo VESL.

Associação entre a razão de monócitos por HDL e TIMI frame count e a trombose de stent em pacientes com primeiro infarto do miocárdio / Association of the monocyte to HDL ratio and TIMI frame count and stent thrombosis in patients with first myocardial infarction

Objetivo: Avaliar a associação entre marcadores de gravidade e complexidade, assim como de desfechos em 30 dias, com a razão de monócitos por HDL em pacientes com primeiro infarto agudo do miocárdio. Métodos: Foram selecionados 580 pacientes com primeiro infarto agudo do miocárdio submetidos a questionário durante a internação e seguimento em 30 dias. Os dados laboratoriais foram obtidos de 312 pacientes na entrada e de 237 em 72 horas. A gravidade e a complexidade foram avaliadas pelo TIMI frame count, pela fração de ejeção do ventrículo esquerdo e pelo escore Syntax. Resultados: O estudo evidenciou correlação positiva entre a razão de monócitos por HDL em 72 horas e o TIMI frame count, com r de 0,219 (p=0,018). Também evidenciou maior mediana de razão de monócitos por HDL nos pacientes que apresentaram trombose de stent em até 30 dias da internação ­ 35,8 (30,0-43,9) ­ comparados àqueles que não apresentaram, com 18,27 (12,98-26,74), p=0,038. Não houve correlação significativa entre a razão de monócitos por HDL da entrada com TIMI frame count, escore SYNTAX ou fração de ejeção do ventrículo esquerdo. Conclusão: Houve correlação positiva entre a razão de monócitos por HDL em 72 horas e o TIMI frame count em pacientes com primeiro infarto agudo do miocárdio submetidos à angioplastia primária. Verificou-se, também, associação entre maiores níveis de razão de monócitos por HDL na entrada com trombose de stent em 30 dias.

Objective: To investigate the association between complexity and severity markers, as well as 30-day outcomes with the monocytes to HDL-cholesterol ratio in patients with first myocardial infarction. Methods: A total of 580 patients with first myocardial infarction was selected and answered a questionnaire during hospitalization and 30-day follow up. Laboratory data were obtained at admission for 312 patients and for 237 in 72 hours. Severity and complexity were assessed by TIMI frame count, left ventricular ejection fraction, and Syntax score. Results: The study showed that the monocyte to HDL ratio in 72 hours was significantly positively correlated with TIMI frame count, with r of 0.219 (p=0.018). It also showed higher monocyte to HDL ratio median in patients presenting stent thrombosis within 30 days of hospitalization ­ 35,8 (30,0-43,9) ­ compared to those who did not develop it 18,27 (12,98-26,74), p=0.038. No correlation was found between admission monocytes to HDL ratio and TIMI frame count, Syntax score, or left ventricular ejection fraction. Conclusion: There was a positive correlation between Monocytes to HDL ratio in 72 hours and TIMI frame count in patients with first myocardial infarction undergoing primary percutaneous coronary intervention. An association between higher levels of admission monocyte to HDL ratio and stent thrombosis in 30 days was also observed.

Evaluation of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio in patients with cellulitis

SUMMARY OBJECTIVE Cellulite infection is a non-necrotizing inflammation of the skin and subcutaneous tissue and is one of the most common reasons for admission to hospital. This retrospective study aimed to investigate the Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Lymphocyte to Monocyte Ratio (LMR) in patients with cellulitis. METHODS In our study, we retrospectively analyzed 96 patients with cellulitis and 98 age- and sex-matched healthy controls. The study and control groups were compared regarding NLR, PLR, and LMR.0.001). When patients with cellulitis were divided into two groups, i.e., ≥65 years and <65 years, a statistically significant difference was noted in the NLR and LMR values (p < 0.05). In the ROC curve analysis, NLR had the highest discriminative power in distinguishing between cellulitis and healthy controls (AUC = 0.950, 95% CI: 0.920-0.979, p < 0.001; 91.6% sensitivity and 89.8% specificity). CONCLUSION NLR was significantly higher in differentiating cellulite and in patients older than 65 years. Larger, prospective studies are required to determine its usefulness in assessing differential diagnosis and prognosis in cellulitis patients.

RESUMO OBJETIVO A celulite infecciosa é uma inflamação não necrotizante da pele e do tecido subcutâneo e uma das causas mais comuns para internação. O objetivo deste estudo retrospectivo foi investigar as relações Neutrófilo/Linfócito (RNL), Plaqueta/Linfócito (RPL) e Linfócito/Monócito (RLM) em pacientes com celulite. MÉTODOS Nós analisamos, retrospectivamente, 96 pacientes com celulite e 98 controles saudáveis equivalentes em sexo e idade. Os grupos foram comparados quanto a RNL, RPL e RLM. RESULTADOS Os valores de RPL e RNL do grupo com celulite foram significativamente mais elevados do que os do grupo de controle (p < 0,001). Após dividir os pacientes com celulite em dois grupos, ≥65 anos e <65 anos, uma diferença estatisticamente significativa foi observada nos valores de RNL e RLM (p < 0,05). Na análise da curva ROC, a RNL apresentou o maior poder de discriminação para distinguir entre pacientes com celulite e controles saudáveis (AUC = 0,950, 95% CI: 0,920 - 0,979; p < 0,001; 91,6% de sensibilidade e 89,8% de especificidade). CONCLUSÃO O valor de RNL foi significativamente maior para a diferenciação de pacientes com celulite e pacientes com mais de 65 anos. Estudos prospectivos maiores são necessários para determinar a sua utilidade na avaliação de diagnósticos diferenciais e prognósticos em pacientes com celulite.

The role of monocyte to HDL ratio in predicting clinically significant carotid stenosis in patients with asymptomatic carotid artery disease

SUMMARY OBJECTIVE Monocyte count to HDL-C Ratio (MHR) and Fibrinogen to Albumin Ratio (FAR) have recently emerged as markers of inflammation in atherosclerotic diseases. Our goal was to investigate the relationships of MHR and FAR with the severity of carotid artery stenosis (CAS) in patients with asymptomatic carotid artery disease. METHODS This retrospective study consisted of 300 patients with asymptomatic CAS. Pre-angiographic MHR, FAR, and high-sensitive C-reactive protein (hsCRP) were measured. Carotid angiography was performed in patients with ≥50% stenosis on carotid ultrasonography. Patients were first split into 2 groups based on the degree of CAS and then tertiles (T) of MHR. RESULTS 96 patients had clinically insignificant CAS (<50%) (Group-1), and 204 patients had clinically significant CAS (≥50%) (Group-2). Group-2 had higher MHR, FAR, and hsCRP than group-1. Patients in T3 had higher MHR, FAR, and hsCRP than in T1 and T2. MHR, FAR, and hsCRP were correlated with each other (p<0.001, for all). MHR, FAR, and hsCRP were independent predictors of significant CAS. MHR better predicted a significant CAS than FAR and hsCRP (p<0.05). CONCLUSION Pre-angiographic MHR may be a better predictor than FAR and hsCRP in identifying a clinically significant carotid stenosis in patients with asymptomatic CAS. Patients with asymptomatic CAS and a high level of MHR should be followed-up closely to supervise risk-factor control and intensify treatment.

RESUMO OBJETIVO Recentemente, a contagem de monócitos para a proporção HDL-C (MHR) e a relação fibrinogênio para albumina (FAR) emergiram como marcadores de inflamação em doenças ateroscleróticas. Nosso objetivo é investigar a relação da MHR e FAR com a gravidade da estenose da artéria carótida (CAS) em pacientes com doença assintomática da artéria carótida. MÉTODOS Este estudo retrospectivo incluiu 300 pacientes com CAS assintomática. MHR pré-angiográfica, FAR e proteína C reativa de alta sensibilidade (hsCRP) foram medidas. A angiografia carotídea foi realizada em pacientes com estenose ≥50% na ultrassonografia carotídea. Os pacientes foram primeiramente divididos em dois grupos com base no grau de CAS e depois nos tercis (T) da MHR. RESULTADOS Noventa e seis pacientes apresentaram um CAS clinicamente insignificante (<50%) (grupo 1) e 204 pacientes apresentaram CAS clinicamente significativo (≥50%) (grupo 2). O grupo 2 apresentou MHR, FAR e hsCRP superior ao grupo 1. Pacientes em T3 apresentaram maior MHR, FAR e hsCRP do que em T1 e T2. MHR, FAR e hsCRP foram correlacionados entre si (p<0,001, para todos). MHR, FAR e hsCRP foram preditores independentes de CAS significativa. MHR predisse melhor uma CAS significativa que FAR e hsCRP (p<0,05). CONCLUSÕES A MHR pré-angiográfica pode ser um melhor preditor que a FAR e a hsCRP na identificação de estenose carotídea clinicamente significativa em pacientes com CAS assintomática. Pacientes com CAS assintomática e alto nível de MHR devem ser acompanhados de perto para supervisionar o controle dos fatores de risco e intensificar o tratamento.