Capacidad pronóstica del PIV (pan-immune-inflammation value) en pacientes con carcinoma escamoso de cabeza y cuello / Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma

Introducción: El PIV (pan-immune-inflammation value), un índice que resulta del cociente (neutrófilos×monocitos×plaquetas) / linfocitos, ha sido propuesto como un biomarcador con capacidad pronóstica en diferentes modelos tumorales. El objetivo del presente estudio es analizar la capacidad pronóstica del PIV en pacientes con carcinoma escamoso de cabeza y cuello. Pacientes y métodos: Estudio retrospectivo de 1.187 pacientes con carcinoma escamoso de cabeza y cuello tratados en nuestro centro durante el periodo 2000-2017. Se obtuvo el valor del PIV a partir de un análisis realizado en un intervalo inferior a las 3 semanas previas al inicio del tratamiento. Resultados: El valor del PIV se relacionó de forma significativa con el consumo de tóxicos (p=0,001), la localización del tumor (0,0001), la extensión tumoral (0,0001), y el grado histológico (0,016). Mediante un análisis de partición recursiva se definieron 4 categorías en función del valor del PIV: categoría i: PIV<136,3 (n=118; 9,9%), categoría ii: PIV 136,3-451,1 (n=594, 50,0%); categoría iii: PIV 451,1-1.141,2 (n=357; 30,1%); categoría iv: PIV>1.141,2 (n=118; 9,9%). Se pudo observar una reducción ordenada y significativa de la supervivencia específica a medida que se incrementaba la categoría en el valor del PIV. Esta disminución en la supervivencia se produjo de forma independiente al tipo de tratamiento, la extensión del tumor, o la localización del tumor primario. La categoría en el valor del PIV se relacionó de forma significativa con la supervivencia específica en un estudio multivariable. Conclusiones: El PIV es un biomarcador con capacidad pronóstica en los pacientes con carcinoma escamoso de cabeza y cuello.(AU)

Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methods: Retrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. Results: PIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. Conclusions: PIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.(AU)

An in vitro analysis of the interaction between infliximab and granulocyte–monocyte apheresis / Análisis in vitro de la interacción entre infliximab y la aféresis de granulocitos y monocitos

Objective: Primary non-response and secondary loss of response to anti-TNF agents are common in inflammatory bowel disease. Increasing drug concentrations are correlated to better clinical response and remission rates. Combination of granulocyte–monocyte apheresis (GMA) with anti-tumor necrosis factor (TNF) agents could be an option in these patients. The objective of our study was to perform an in vitro assay to determine if the GMA device can lead to infliximab (IFX) adsorption. Patients and methods: A blood sample was obtained from a healthy control. It was incubated with three concentrations of IFX (3, 6, and 9μg/ml) at room temperature for 10min. At that time, 1ml was collected to determine the IFX concentration. Then, 10ml of each drug concentration was incubated with 5ml of cellulose acetate (CA) beads from the GMA device at 200rpm for 1h at 37°C to simulate physiological human conditions. A second sample of each concentration was collected and IFX levels were determined. Results: No statistically significant differences were observed in the IFX levels in the blood samples before and after incubation with the CA beads (p=0.41) and after repeated measurements (p=0.31). Mean change was 3.8μg/ml. Conclusions: The in vitro combination of GMA and IFX did not change the circulating levels of IFX at the three concentrations tested, suggesting that there is no interaction between the drug and the apheresis device in vitro and that they might be safely combined with each other. (AU)

Objetivo: La falta de respuesta primaria y la pérdida de respuesta secundaria a los agentes antifactor de necrosis tumoral (TNF) son comunes en la enfermedad inflamatoria intestinal. El aumento de los niveles de fármaco se correlaciona con una mejor respuesta clínica y de las tasas de remisión. La combinación de la aféresis selectiva de granulocitos y monocitos (GMA) con agentes anti-TNF podría ser una opción en estos pacientes. El objetivo de nuestro estudio fue realizar un ensayo in vitro para determinar si el dispositivo de GMA puede interaccionar con infliximab (IFX). Pacientes y métodos: Se obtuvo una muestra de sangre de un control sano. Se incubó con 3 concentraciones de IFX (3, 6 y 9μg/ml) a temperatura ambiente durante 10 minutos. En ese momento, se recogió 1ml para determinar la concentración de IFX. Luego, se incubaron 10ml de cada concentración de fármaco con 5ml de cuentas de acetato de celulosa del dispositivo GMA a 200rpm durante una hora a 37°C para simular las condiciones fisiológicas humanas. Se recogió una segunda muestra de cada concentración y se determinaron los niveles de IFX. Resultados: No se observaron diferencias estadísticamente significativas en los niveles de IFX en las muestras de sangre antes y después de la incubación con las cuentas de acetato de celulosa (p=0,41) ni tras mediciones repetidas (p=0,31). La media de cambio fue de 3,8μg/ml. Conclusiones: La combinación in vitro de IFX y GMA no modificó los niveles circulantes del fármaco en las 3 concentraciones probadas, lo que indica que no existe interacción entre el fármaco y el dispositivo de aféresis in vitro y que podrían combinarse de forma segura. (AU)

The Prognostic Value of the Combination of the Prognostic Nutritional Index and the Lymphocyte: Monocyte Ratio for the Prediction of Patients with Muscle-Invasive Bladder Cancer

Objective: To explore the efficacy of combining the prognostic nutritional index (PNI) and the lymphocyte:monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC). Methods: Of 172 patients who were diagnosed with MIBC in our hospital, 94 were eligible for the study. The clinical data of the 94 patients with MIBC were collected. The patients were divided according to the optimal cut-off values for the preoperative PNI and LMR into a low-PNI subgroup (PNI <44.15, 52 patients), a high-PNI subgroup (PNI ≥44.15, 42 patients), a low-LMR subgroup (LMR <2.98, 50 patients) and a high-LMR subgroup (LMR ≥2.98, 44 patients). The area under the receiver operating characteristic (ROC) curve (AUC) was used to analyse the efficacy of the PNI and the LMR in predicting the prognosis of patients with MIBC. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for patients with MIBC. Kaplan–Meier (K‒M) survival analysis was used for overall survival (OS) analysis to explore the ability of the PNI combined with the LMR to predict the prognosis of patients with MIBC. Results: The optimal cut-off values for the preoperative PNI and the preoperative LMR were 44.15 and 2.98, respectively, on the basis of ROC curves. ROC curve analysis revealed that the PNI (AUC = 0.720, sensitivity 65.9%, specificity 74.50%, Youden index 0.399) and the LMR (AUC = 0.724, sensitivity 65.9%, specificity 70.0%, Youden index 0.395) both had good prognostic efficacy for patients with MIBC. The results of univariate and multivariate logistic regression analyses showed that preoperative PNI <44.15 was an independent risk factor for OS in patients with MIBC (p = 0.027). Based on K‒M survival curve analysis, patients with PNI <44.15 and LMR <2.98 had the shortest OS (p = 0.00002). Conclusions: Low preoperative PNI and LMR values are indicative of poor prognosis in patients with MIBC...(AU)

Utilidad de los índices celulares y el índice neutrófilo/linfocito derivado en el diagnóstico de la apendicitis aguda pediátrica / Usefulness of cell ratios and the derived neutrophil- to-lymphocyte ratio in the diagnosis of pediatric acute appendicitis

Objetivo: Analizar la precisión de los índices celulares en el diagnóstico de la apendicitis aguda pediátrica, introduciendo uno nuevo, el índice neutrófilo/linfocito derivado (INLd). Material y métodos: Estudio retrospectivo observacional de los pacientes de 0-15 años diagnosticados de apendicitis aguda (AA) y con dolor abdominal no quirúrgico (DA) tratados en nuestro centro entre 2021-2022. Se comparó el índice neutrófilo/linfocito (INL), índice monocito/linfocito (IML), índice plaqueta/linfocito (IPL) y el INLd entre los grupos. Resultados: Se incluyeron 98 casos con AA (30% mujeres, edad 10 ± 3,3 años) y 97 pacientes con DA (53% hombres, edad 9,3 ± 3,7 años). Los valores de INL, IML, IPL e INLd fueron mayores en pacientes con AA respecto a niños con DA: 9,6 rango intercuartil (RIC) 9,5 vs. 3,3 RIC 5,3: p = < 0,0001; 0,7 RIC 0,6 vs. 0,46 RIC 0,7: p = < 0,023; 199,8 RIC 163,9 vs. 134,0 RIC 129,2: p = < 0,0001; y 5,29 RIC 3,9 vs. 2,39 RIC 2,7: p = < 0,0001; respectivamente. La sensibilidad, especificidad, valor predictivo positivo-negativo, área bajo la curva ROC y el punto de corte del INLd para el diagnóstico de AA fue de 70%, 78%, 77-72%, 0,811 y 3,98; respectivamente. Conclusiones. Los índices celulares son parámetros inflamatorios útiles y coste-efectivos que pueden contribuir al diagnóstico de la apendicitis aguda pediátrica. Los resultados de este estudio sugieren que el INLd es el de mayor precisión clínica.(AU)

Objective: To analyze the accuracy of cell ratios in the diagnosis of pediatric acute appendicitis while introducing a new one – the derived neutrophil-to-lymphocyte ratio (dNLR). Materials and methods: An observational, retrospective study of patients aged 0-15 years old diagnosed with acute appendicitis (AA) and with non-surgical abdominal pain (AP) treated in our institution from 2021 to 2022 was carried out. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and dNLR were compared between groups. Results. 98 AA patients (30% of whom were female; age: 10 ± 3.3 years) and 97 AP patients (53% of whom were male; age: 9.3 ± 3.7 years) were included. NLR, MLR, PLR, and dNLR values were higher in AA patients than in AP patients: 9.6 IQR (interquartile range) 9.5 vs. 3.3 IQR 5.3: p < 0.0001; 0.7 IQR 0.6 vs. 0.46 IQR 0.7: p < 0.023; 199.8 IQR 163.9 vs. 134.0 IQR 129.2: p < 0.0001; and 5.29 IQR 3.9 vs. 2.39 IQR 2.7; p < 0.0001, respectively. Sensitivity, specificity, positive-negative predictive value, area under the ROC curve, and dNLR cut-off point for AA diagnosis were 70%, 78%, 77-72%, 0.811, and 3.98, respectively. Conclusions. Cell ratios are useful and cost-effective inflammatory parameters in the diagnosis of pediatric acute appendicitis. The results of this study suggest dNLR has the greatest clinical accuracy.(AU)

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)

Cervical carcinoma induces NLRP3 inflammasome activation and IL-1ß release in human peripheral blood monocytes affecting patients’ overall survival

Purpose Our group previously demonstrated that genetic variants in inflammasome genes contribute to protection against the establishment of human papilloma virus (HPV)-associated cervical carcinoma (CC). The objective of this study was to better understand the contribution of inflammasome and its cytokines in the CC microenvironment. Methods The inflammasome activation was analyzed in CC tumoral cell lines and healthy donors (HD)’ monocytes in co-culture. In vitro results were then compared to CC patients’ public databases. Results CC cells did not produce IL-1ß or IL-18 themselves, however, when in co-culture with HD monocytes, induced IL-1ß release in those leucocytes. Inflammasome activation appears to be partially dependent on the NLRP3 receptor. Public data analysis revealed that IL1B expression is increased in the CC compared to normal uterine cervix, and that patients with high IL1B expression had a shorter overall survival. Conclusion CC microenvironment can activate the inflammasome and IL-1ß release in surrounding monocytes, which could be detrimental for CC prognosis (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)

Study on the predictive value of MHR combined with thromboelastography parameters for acute cerebral infarction in athlete players

Aims: To investigate the predictive value of peripheral blood monocyte count and high density lipoprotein cholesterol (HDL-C) ratio (monocyte/HDL-C, MHR) combined with thromboelastography (TEG) related parameters in acute Cerebral infarction (ACI). Methods: The study group included 201 patients with ACI, and the comparison group included 201 patients with non-ACI. Using dispersion analysis, changes in MHR and TEG were compared between the two groups. Using logistic regression analysis, valuable measures of model building were screened. Using receiver operating characteristic (ROC) curves, the predictive effect of a combination of single and multiple indices on ACI was evaluated. Based on NIHSS scores, the research team was also divided into a mild nerve injury group (152 cases) and a moderate to severe nerve injury group (49 cases). Compare the changes in the two groups of indicators. Correlations between NIHSS scores and each index were analyzed by pearson correlation. Reasults: Lymphocyte count, monocyte count, MHR, angle, MA, G and A30 were higher in the study group than in the control group. HDL-C, NLR, R and K values were lower in the study group than in the control group, and the differences were statistically significant (P<0.05). Among the indicators, MHR had the highest diagnostic concordance rate and area under the curve (AUC) (0.806 and 0.883, respectively), the highest sensitivity (0.891) for the count of monocyte , and the highest R-value specificity (0.776). Logistic regression analysis showed that MHR>0.367, monocyte count >0.38×109/L, A30>63.1mm and R value<5.0min were independent risk factors for ACI. The 4-factor regression equation has been established: logit(P)=-2.19+1.541* monocyte count -1.731*R+1.466*A30+2.040*MHR. (AU)

The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer

Background: The clinicopathological and prognostic relevance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in non-muscular invasive bladder cancer (NMIBC) was investigated. Methods: All patients who underwent transurethral resection of bladder tumor (TURBT) and postoperative intravesical chemotherapy had their peripheral blood levels of NLR, PLR, and MLR quantified. The preoperative peripheral blood levels of NLR, PLR, and MLR were analyzed in patients with G1, G2, and G3 NMIBC. A total of 208 patients was divided into poor prognosis (PP, with recurrence, n=51) and good prognosis (GP, no recurrence, n=157) groups, according to whether the recurrence of NMIBC was observed at 1-year follow-up after treatment. Univariate and multivariate logistic regression analyses were performed to evaluate the prognostic factors in NMIBC. In addition, receiver operating characteristic (ROC) curves were used to analyze the prognostic performance of NLR, PLR, and MLR in NMIBC. Results: The preoperative peripheral blood level of PLR was significantly increased in patients with G3 NMIBC compared with that in patients with G1 (p < 0.05) and G2 NMIBC (p < 0.05). The results of univariate and multivariate logistic regression analyses showed that the tumor diameter, differentiation grade, and preoperative peripheral blood levels of NLR, PLR, and MLR were independent prognostic factors for NMIBC recurrence (p < 0.05). Compared with the NMIBC patients without recurrence, 3.490%, 177.575% and 3.175% were determined as the optimum prognostic cutoffs for NLR, PLR, and MLR, respectively. ROC curve was used to evaluate the sensitivity, specificity, and area under the curve (AUC) of NLR, PLR, MLR, and combinations. In contrast to NLR, PLR, or MLR, the combination of NLR, PLR, and MLR (AUC 0.758, sensitivity 66.70%, specificity 89.80%,Youden index 0.565) (AU)

Usefulness of peripheral blood monocyte count to predict relapse in patients with inflammatory bowel disease: a prospective longitudinal cohort study

Background: monocytes play an important role in the pathogenesis of inflammatory bowel disease but data are scarce regarding activity biomarkers, above all in patients under biologic therapies.Objective: the aim of this study was to evaluate the value of monocyte measurements in predicting flares in inflammatory bowel disease patients under maintenance treatment with anti-TNF.Methods: a prospective, observational cohort study was designed. Relapse was defined as a Harvey-Bradshawscore > 4 in Crohn’s disease, and a partial Mayo score ≥ 2 in ulcerative colitis. Monocyte concentration was quantifiedat 4-month intervals for twelve months. A total of 95 consecutive patients were included. Median age was 42 years,50.5 % were female, and 75 % had Crohn’s disease.Results: sixteen months after inclusion, 65 (68.4 %) patients remained in clinical remission. Mean monocyte count preceding a relapse was 563 (standard deviation: 144) compared to 405 (standard deviation: 177) in patients who remained in remission. Final monocyte count was significantly different between relapse and remission in Crohn’s disease (0.82; 95 % CI: 0.71-0.90; p < 0.005). According to the multivariate analysis, only monocytes and fecal calprotectin were related to more relapses. (AU)

Perturbation of monocyte subsets in iron-deficient children – a shift to a pro-inflammatory state?

Background Iron deficiency anemia (IDA) is the most prevalent micronutrient deficiency in preschool children in developing countries including India. IDA is associated with immune perturbation, which is reflected in greater frequency of infections in these children. Recent research has shown three distinct monocyte subsets with distinct functions linked to infectious, inflammatory, and autoimmune diseases. These subsets have not been studied in children with IDA. Objective The aim of the study was to assess the percentage of monocyte population and the three subset populations in children with IDA and to compare the data with age-matched healthy controls. Methods Venous blood samples (5 mL) from 40 IDA children and 20 controls were collected after taking informed consent. Monocyte subpopulations were compared across the two groups. The outcome variables were calculated using Students Independent t-test or Mann–Whitney U test. P value of <0.05 was taken as significant. Results No significant difference was found in the absolute numbers as well as percentages of total monocytes between the control and case (study) group. Children in the IDA group showed a significant (p = 0.03) decrease in the nonclassical subset population when compared to the control group. Conclusion This is the first study done on monocyte subsets in iron-deficient children. Decrease in nonclassical monocytes observed may be associated with a pro-inflammatory state and increased risk of inflammatory and auto immune diseases. Follow-up studies are needed to confirm these findings (AU)

Reference values of leukocyte and lymphocytes populations in umbilical cord and capillary blood in healthy Mexican newborns

INTRODUCTION: In newborns, dramatic changes occur in the blood and bone marrow during the first hours; there are rapid fluctuations in the quantities of leukocytes populations. In this work, we investigated leukocytes subsets counts in two types of blood samples (cord blood and capillary blood) extracted from healthy newborns. METHODS: Blood samples from Mexican neonates were collected by Instituto Nacional de Pediatría with written informed consent. For all samples we determined leukocytes populations; neutrophils, monocytes, total lymphocytes, and populations: T CD3+ cells, TCD4+ cells, T CD8+ cells, B CD19+ cells and NK CD16+56 cells by flow cytometry. We used the Mann-Whitney U test to compare leukocytes of cord and capillary blood; also to analyze the differences between gender and we obtained reference values of the cord and capillary blood in neonates. RESULTS: We observed higher absolute counts and frequencies of total lymphocyte in capillary blood compared with cord blood. In absolute numbers, the capillary blood showed significant differences in neutrophils, monocytes, lymphocytes, T CD3+ cells, T CD4+ cells, T CD8+ cells, B CD19+ cells, and NK cells; no significant differences were observed between genders. DISCUSSION: Our data contribute to newborn Mexican reference values for all these populations of leukocytes. We found that the dispersal range differs between the two types of blood, suggesting a different fate in the immune response. Immunophenotyping of the blood cell population to identify these cells is an essential tool in the diagnosis and follow-up of neonates with immunodeficiencies and other immune disorders

No disponible

Resistance training and innate immunosenescence of the innate immune system / Entrenamiento de resistencia e inmunosenescencia del sistema inmune innato / Treinamento resistido e imunossenescência do sistema imune inato

Phagocytic cells constitute the first defense line against the diversity of infectious agents. The effects of aging on the immune function - immunosenescence - affect the phagocytic capacity of neutrophils and monocytes/macrophages and result in increased risk to cancer and other diseases. The aim of this review was to assess the functional aspects of the innate system cells in aging. Evidence brought about by this review suggests that resistance training is a useful therapy to mitigate the adverse effects of the innate immune system aging process. Resistance training is consistently recommended as assistent strategy for prevention of the inflamaging and associated chronic diseases, but establishing adequate program is still in demand. In addition, future studies are needed to improve our understanding of the resistance training-induced mechanisms underlying changes in phagocytic activity in the elderly

Las células fagocíticas constituyen la primera línea de defensa contra los agentes infecciosos. Los efectos del envejecimiento sobre la función inmune - inmunosenescencia - afectan la capacidad fagocítica de neutrófilos y monocitos/macrófagos y resultan en riesgo aumentado para el cáncer y otras enfermedades. El objetivo de esta revisión fue evaluar los aspectos funcionales de las células del sistema innato en el envejecimiento. Las evidencias revisadas sugieren que el entrenamiento de resistencia es una terapia útil para atenuar los efectos adversos del proceso de envejecimiento del sistema inmune innato. Se recomienda el entrenamiento de resistencia continuamente como estrategia complementaria para la prevención de la inflamación y de las enfermedades crónicas asociadas, pero hay que establecer el programa adecuado. Además, se necesitan más investigaciones para mejorar nuestra comprensión de los mecanismos modulados por el entrenamiento de resistencia que inducen a los cambios en la actividad fagocítica en las personas mayores

As células fagocitárias constituem a primeira linha de defesa contra agentes infecciosos. Os efeitos do envelhecimento sobre a função imune - imunossenescência - afetam a capacidade fagocítica de neutrófilos e monócitos/macrófagos e resultam em aumento do risco para câncer e outras doenças. O objetivo desta revisão foi avaliar os aspectos funcionais das células do sistema inato durante o envelhecimento. Os estudos revisados sugerem que o treinamento resistido é uma terapia útil para atenuar os efeitos adversos do processo de envelhecimento do sistema imune inato. Recomenda-se que o treinamento resistido seja aplicado continuamente como estratégia complementar para a prevenção da inflamação e doenças crônicas associadas, porém deve-se estabelecer o programa adequado. Ressalta-se ainda que, são necessários mais estudos para melhorar a compreensão sobre os mecanismos modulados pelo treinamento resistido que induzem a alterações na atividade fagocítica em idosos

Análisis de subpoblaciones monocitarias en relación con los factores de riesgo cardiovascular / Analysis of monocitary subpopulations in relation to cardiovascular risk factors

Introducción: La participación monocitaria en la progresión aterosclerótica y sus efectos pro- o antiinflamatorios dependen de las subpoblaciones circulantes. El objetivo de este estudio es la caracterización de dichas subpoblaciones y su asociación con los factores de riesgo cardiovascular. Métodos: Estudio transversal que incluye 102 pacientes seleccionados; edad media: 65 años (rango 41-86 años), 69% varones. Se utilizó un panel de anticuerpos específicos frente a monocitos clásicos (Mon1, CD14+CD16− CD300e+HLADR+), intermedios (Mon2, CD14+CD16+CD300e+HLADR+) y no clásicos (Mon3, CD14-k-CD16+CD300e+HLADR+). Se establecieron tres grupos de estudio; grupo 1: sujetos asintomáticos con más de un factor de riesgo cardiovascular (n = 17); grupo 2: sujetos asintomáticos, pero con patología vascular por ecografía o microalbuminuria (n = 56); y grupo 3: pacientes con algún evento vascular aterotrombótico previo (n = 19). Asimismo, se calculó el riesgo cardiovascular mediante las escalas Framingham y REGICOR. Resultados: Se observó una asociación entre las subpoblaciones Mon1 y Mon2 y los grupos del estudio (ANOVA, p < 0,05), independiente de la edad y el sexo para los Mon2. Asimismo, las subpoblaciones Mon1 y Mon 2 se asociaron con eventos vasculares adversos (ß = 0,86, p = 0,02 y ß = 0,1 p = 0,002, respectivamente), siendo la asociación de Mon2 independiente de la edad y el sexo. Además, el porcentaje de Mon3 se asoció con la presencia de más de 2 factores de riesgo cardiovascular (ß=0,21, p=0,04) en el análisis univariante. Finalmente, se halló una correlación entre los niveles de Mon1 y Mon2 con el número de leucocitos (r = 0,7, p < 0,001 y r = 0,26 p < 0,01, respectivamente). Conclusiones: El análisis de subpoblaciones monocitarias es de gran interés clínico, ya que permite establecer un diferente perfil inflamatorio según los grupos de riesgo cardiovascular establecidos

Introduction: Monocytes play an important role in atherosclerotic progression having both pro and anti-inflammatory effects depending on different circulating monocyte subpopulations. The objective of this study is to characterize these subpopulations and their association with cardiovascular risk factors. Methods: Transversal study including 102 selected patients, mean age: 65 years-old (range 41-86), 69% males. A set of specific antibodies against classical monocytes (Mon1, CD14+CD16- CD300e+HLADR+), intermediate (Mon2, CD14+CD16+CD300e+HLADR+) and non-classical (Mon3, CD14-CD16+CD300e+HLADR+) was assayed. Three groups of patients were included: 17 asymptomatic with more than one cardiovascular risk factor (group 1), 56 subjects asymptomatic but with vascular pathology assessed by ultrasound or microalbuminuria (group 2) and 19 patients with a previous atherothrombotic event (group 3). The cardiovascular risk was determined by Framingham and REGICOR scores. Results: An association between study groups and the percentage of Mon1 and Mon2 was observed (ANOVA, p < .05), being independent of age and sex for Mon2. Likewise Mon1 and Mon2 subpopulations were associated with cardiovascular adverse events (ß = 0.86, p =.02 y ß = 0.1 p =.002, respectively), independently of age and sex in the case of Mon2. Moreover the percentage of Mon3 was associated with the presence of several cardiovascular risk factors (ß = 0.21, p = .04) in the univariate analysis. In addition, there was a correlation between the levels of Mon1 and Mon2 and leukocytes (r = 0.7, p < .001 and r = 0.26, p = .01, respectively). Conclusions: The analysis of monocyte subpopulations may be clinically useful to stratify the inflammatory profile related to the different cardiovascular risk groups

Nuevos mecanismos en la trombosis venosa: inmunotrombosis / New mechanisms in vein thrombosis: Immunothrombosis

No disponible

Regulatory roles of miR-155 and let-7b on the expression of inflammation-related genes in THP-1 cells: effects of fatty acids

The main aim of this investigation was to study the regulatory roles of let-7b and miR-155-3p on the expression of inflammation-associated genes in monocytes, macrophages, and lipopolysaccharide (LPS)-activated macrophages (AcM). A second goal was to analyze the potential modulatory roles of different fatty acids, including oleic, palmitic, eicosapentaenoic (EPA), and docosahexaenoic (DHA), on the expression of these miRNAs in the three cell types. This hypothesis was tested in human acute monocytic leukemia cells (THP-1), which were differentiated into macrophages with 2-O-tetradecanoylphorbol-13-acetate (TPA) and further activated with LPS for 24 h. Monocytes, macrophages, and AcM were transfected with a negative control, or mimics for miR-155-3p and miR-let-7b-5p. The expression of both miRNAs and some proinflammatory genes was analyzed by qRT-PCR. Interestingly, let-7b mimic reduced the expression of IL6 and TNF in monocytes, and SERPINE1 expression in LPS-activated macrophages. However, IL6, TNF, and SERPINE1 were upregulated in macrophages by let-7b mimic. IL6 expression was higher in the three types of cells after transfecting with miR-155-3p mimic. Similarly, expression of SERPINE1 was increased by miR-155-3p mimic in monocytes and macrophages. However, TLR4 was downregulated by miR-155-3p in monocytes and macrophages. Regarding the effects of the different fatty acids, oleic acid increased the expression of let-7b in macrophages and AcM and also increased the expression of miR-155 in monocytes when compared with DHA but not when compared with non-treated cells. Overall, these results suggest anti- and proinflammatory roles of let-7b and miR-155-3p in THP-1 cells, respectively, although these outcomes are strongly dependent on the cell type. Noteworthy, oleic acid might exert beneficial anti-inflammatory effects in immune cells (i.e., non-activated and LPS-activated macrophages) by upregulating the expression of let-7b

Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients' point of view / Granulocito-monocito aféresis en la enfermedad inflamatoria intestinal: el punto de vista de los pacientes

BACKGROUND: Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. AIM: To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. METHODS: Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. RESULTS: Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23-51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients' clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. CONCLUSIONS: Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness

INTRODUCCIÓN: La leucocitoaféresis constituye el principal tratamiento no farmacológico para la enfermedad inflamatoria intestinal (EII), pero no conocemos su grado de aceptación por los pacientes en nuestro entorno. OBJETIVO: Conocer la percepción de los pacientes sobre la leucocitoaféresis en la práctica clínica en España. MÉTODOS: Se ofreció un cuestionario de 14 preguntas a los pacientes ambulatorios tratados con leucocitoaféresis en 5 unidades de EII en España. RESULTADOS: Cincuenta y dos pacientes respondieron el cuestionario (88% colitis ulcerosa, 12% enfermedad de Crohn; 44% mujeres, 35 años [RIQ: 23-51]). La leucocitoaféresis fue bien tolerada de forma global y con un alto grado de aceptación. La mayoría de pacientes no percibía la duración de las sesiones como una limitación. En cambio, los síntomas digestivos eran una preocupación habitual, tanto para acudir al tratamiento como durante las sesiones. Un 44% estaban satisfechos con la efectividad del tratamiento. El 60% contestaron que estaban satisfechos con la técnica de forma global, pero esto estaba influenciado por la respuesta clínica que habían experimentado. Un 82% estarían dispuestos a ser tratados de nuevo con la técnica, independientemente de la respuesta al tratamiento. CONCLUSIONES: La leucocitoaféresis es una técnica bien tolerada y aceptada por los pacientes con EII. A pesar de que no encontramos diferencias según el tipo de EII o la pauta de tratamiento, sí encontramos una percepción diferente según la efectividad de la técnica

Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy

Background. Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT. Methods. A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS). Results. Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress. Conclusion. High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT (AU)

No disponible

Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy

The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy (AU)

No disponible