Pulmonary Function in People Living With Human Immunodeficiency Virus: A Meta-Analysis

Background: HIV can infect bronchial epithelial cells rendering individuals susceptible to lung damage. Our objective was to determine the effects of human immunodeficiency virus (HIV) infection on pulmonary function tests. Methods: We performed a meta-analysis after conducting a literature search in PubMed, Embase, Cochrane Library and Virtual Health Library databases from inception to December 31st, 2022. We employed the inverse variance method with a random effects model to calculate the effect estimate as the mean difference (MD) and 95% confidence interval (CI). We calculated the heterogeneity with the I2 statistic and performed a meta-regression analysis by age, sex, smoking, CD4 T-cells count and antiretroviral therapy. We also conducted a sensitivity analysis according to the studies’ publication date, and excluding the study with the greatest weight in the effect. The PROSPERO registry number was CRD42023401105. Results: The meta-analysis included 20 studies, with 7621 living with HIV and 7410 control participants. The pooled MD (95%CI) for the predicted percentage of FEV1, FVC and DLCO were −3.12 (−5.17, −1.06); p=0.003, −1.51 (−3.04, 0.02); p=0.05, and −5.26 (−6.64, −3.87); p<0.001, respectively. The pooled MD for FEV1/FVC was −0.01 (−0.02, −0.01); p=0.002. In all cases, there was a considerable heterogeneity. The meta-regression analysis showed that among studies heterogeneity was not explained by patient age, smoking, CD4 T-cells count or antiretroviral therapy. Conclusion: Pulmonary function tests are impaired in people living with HIV, independently of age, smoking, CD4 T-cells count, and geographical region. (AU)

Recuento de neutrófilos asociado al fenotipo Duffy nulo / Neutrophil count associated with the Duffy phenotype null

Introducción. El fenotipo Duffy nulo es una variante de la normalidad de los antígenos de membrana de las células sanguíneas que ocasiona la forma más frecuente de neutropenia congénita a nivel mundial. Los individuos que la poseen, mayoritariamente provenientes de regiones de África subsahariana, presentan de forma persistente recuentos de neutrófilos por debajo del rango normal, sin que esto implique aumento en el riesgo de infecciones. Caso clínico. Presentamos un lactante, seguido en nuestro Servicio de Neonatología, por neutropenia persistente desde el nacimiento, hijo de una madre procedente de Guinea Ecuatorial. Tras varias analíticas se pudo comprobar el diagnóstico de neutropenia congénita asociada a Duffy nulo a través de inmunofenotipo de sangre periférica. La evolución del niño fue satisfactoria y no presentó ninguna complicación por su neutropenia. Conclusiones. Se debe clasificar la Neutropenia Congénita Asociada a Duffy Nulo (DANC, en sus siglas en inglés) como un polimorfismo genético que genera una variante de la normalidad, adecuando los rangos de los recuentos de neutrófilos a la misma. No se ha visto aumento en el riesgo de infecciones o enfermedades autoinmunes, ni alteraciones en la función de los neutrófilos. Considerar a estos pacientes con los rangos normales de la mayoría de la población tiene consecuencias como pruebas innecesarias, exclusión de ensayos clínicos o no administración de tratamientos oncológicos (AU)

Introduction. The Duffy-null phenotype is a variant of normal blood cell membrane antigens that causes the most frequent form of congenital neutropenia worldwide. Individuals who have it, mostly from sub-Saharan Africa, persistently have neutrophil counts below the normal range, without this implying an increased risk of infections. Case report. We present a child, followed in our Neonatology Service, due to persistent neutropenia from birth, son of a mother from Equatorial Guinea. After several tests, the diagnosis of congenital neutropenia associated with Duffy null could be verified through peripheral blood immunophenotyping. The evolution of the child was satisfactory and he did not present any complications due to his neutropenia Conclusions. Duffy-Null Associated Congenital Neutropenia (DANC) should be classified as a genetic polymorphism that generates a variant of normality, adapting the ranges of neutrophil counts to it. There has been no increase in the risk of infections or autoimmune diseases, nor alterations in the function of neutrophils. Considering these patients within the normal ranges of the majority of the population has consequences such as unnecessary tests, exclusion from clinical trials, or non-administration of oncological treatments (AU)

A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma

Purpose Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC). Methods Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model. Results Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG’s effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression. Conclusion We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC (AU)

Prognostic value of neutrophil–lymphocyte ratio in critically ill patients with cancer: a propensity score matching study

Background Neutrophil–lymphocyte ratio (NLR) has shown a good prognostic value in many different type of malignancies. The purpose of this study was to investigate the relationship between NLR and the outcome of critically ill patients with cancer. Methods We performed a single-institution, retrospective study of 1317 adult critically ill patients with cancer and determined the optimal cut-off for NLR by X-tile software. Propensity score matching (PSM) and inverse probabilities of treatment weighting (IPTW) were performed to control confounders. Cox proportional hazards model was used to evaluate the relationship between NLR and 28-day, 6-month and 1-year all-cause mortality. Kaplan–Meier method, subgroup analysis, and receiver operating characteristics (ROC) analysis were applied to assess the prognostic value of NLR. Results The cut‐off value for NLR was 17.6. Cox proportional hazards model demonstrated that high NLR (> 17.6) was independently associated with 28-day, 6-month and 1-year all-cause mortality with hazard ratio (HR) of 1.58 (1.29, 1.94), 1.51 (1.28, 1.77) and 1.45 (1.25, 1.69), respectively. The results were consistent with survival analyses (p < 0.001, log-rank test). The ROC analyses showed that the discrimination abilities of NLR were better than other blood-based biomarkers. Conclusion NLR is a promising prognostic indicator of survival in unselected critical ill patients with cancer (AU)

Assessment of Induced Sputum Cellularity in COPD Patients Belonging to Two Different Classes of Air Pollution Exposure / Estudio de la celularidad en el esputo inducido de pacientes con EPOC expuestos a dos niveles diferentes de contaminación atmosférica

INTRODUCTION: Several studies have previously demonstrated that long-term exposure to outdoor pollution present airway inflammation in term of an increase of sputum neutrophils. AIM AND METHODS: The aim of our study was to evaluate the level of airway inflammation by induced sputum in a group of 15 non-professionally exposed population of well-characterized COPD patients, residing in urban areas with high rate of outdoor pollution, compared to a control group of 13 individuals with COPD, living in rural areas with a low pollution rate. All participants underwent spirometry and sputum induction. RESULTS: A statistically significant increase in the percentage of neutrophil cell count was found among the residents in urban areas compared to those living in rural regions (89.1 vs 79.0, p < 0.05). CONCLUSIONS: In conclusion, we showed that non-professionally exposed patients with COPD residing in highly-polluted urban areas had greater airway inflammation in terms of sputum neutrophils compared to a population with very similar characteristics, living in rural areas with lower outdoor pollution. The results of this pilot study may be relevant for the long term effect of environmental outdoor pollution in vulnerable patients like those with COPD

INTRODUCCIÓN: Varios estudios han demostrado con anterioridad que la exposición a la contaminación atmosférica a largo plazo provoca una inflamación de la vía aérea que se ve reflejada en un aumento de neutrófilos en el esputo. OBJETIVO Y MÉTODOS: El objetivo de nuestro estudio fue estimar el grado de inflamación de la vía aérea a través del esputo inducido en un grupo de 15 pacientes con EPOC bien caracterizada sin exposición por motivos profesionales y residentes en áreas urbanas con un nivel alto de contaminación atmosférica, comparados con un grupo control de 13 individuos con EPOC que vivían en zonas rurales con un nivel de contaminación atmosférica bajo. A todos los pacientes se les sometió a una espirometría y a una inducción del esputo. RESULTADOS: Se encontró un aumento estadísticamente significativo en el porcentaje de recuento celular de neutrófilos de los residentes en áreas urbanas en comparación con aquellos que vivían en zonas rurales (89,1 frente a 79,0%, p < 0,05). CONCLUSIONES: En conclusión, demostramos que los pacientes con EPOC que no estaban expuestos debido a su profesión y residentes en áreas urbanas con alta contaminación atmosférica presentaban mayor inflamación de la vía aérea en cuanto al número de neutrófilos en esputo en comparación con una población de características muy similares residente en zonas rurales con menos contaminación atmosférica. El resultado de este estudio piloto podría ser relevante para el efecto a largo plazo de la contaminación atmosférica exterior en pacientes especialmente vulnerables como pueden ser aquellos con EPOC

Th17 cells in Bulgarian children with chronic obstructive lung diseases

Introduction and objectives: Th17 lymphocytes are now widely believed to be critical in various chronic pulmonary diseases. However, there is still a small number of investigations regarding children. We aimed to assess the percentage of Th17 lymphocytes and IL-17A in peripheral blood of children with chronic obstructive lung diseases. Patients and methods: We included a total of 42 children: 20 with bronchial asthma (BA), 12 with cystic fibrosis (CF) and 10 healthy children without a history of allergies, aged 4-17 years. Th17 cells (CD3 + CD4 + CD161 + CCR6+) were determined in peripheral blood by flow cytometry. The concentration of serum IL-17A was measured by ELISA. Results: The BA patients had a significantly higher percentage of Th17 (12.40 ± 1.16%) compared to the CF children (7.64 ± 0.87%, p = 0.0035) and healthy (7.25 ± 0.45%, p = 0.008). Stratifying the BA group, we found higher levels of Th17 in patients with severe BA (p = 0.03), whereas patients with moderate BA had Th17 cells close to those in CF and healthy children. We found that patients with better control of BA had Th17 closer to those with CF (p = 0.98) than BA children with poor control (p<0.001) (post hoc, Bonferroni correction). CF patients with concomitant P. aeruginosa infection showed slightly higher percentages of Th17 cells than those without infection (8.08 ± 3.09% vs. 6.25 ± 2.42%, p = 0.294). Conclusions: The percentage of Th17 cells was significantly increased in the peripheral blood of children with severe BA compared to the children with moderate BA, which suggests that the former could possibly benefit from future target therapies

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Comparison of manual & automated analysis methods for corneal endothelial cell density measurements by specular microscopy / Comparación de los métodos de análisis manual y automatizado para medir la densidad celular endotelial corneal mediante microscopio especular

Purpose: To determine the reliability of corneal endothelial cell density (ECD) obtained by automated specular microscopy versus that of validated manual methods and factors that predict such reliability. Methods:Sharp central images from 94 control and 106 glaucomatous eyes were captured with Konan specular microscope NSP-9900. All images were analyzed by trained graders using Konan CellChek Software, employing the fully- and semi-automated methods as well as Center Method. Images with low cell count (input cells number <100) and/or guttata were compared with the Center and Flex-Center Methods. ECDs were compared and absolute error was used to assess variation. The effect on ECD of age, cell count, cell size, and cell size variation was evaluated. Results:No significant difference was observed between the Center and Flex-Center Methods in corneas with guttata (p = 0.48) or low ECD (p = 0.11). No difference (p = 0.32) was observed in ECD of normal controls < 40 yrs old between the fully-automated method and manual Center Method. However, in older controls and glaucomatous eyes, ECD was overestimated by the fully-automated method (p = 0.034) and semi-automated method (p = 0.025) as compared to manual method. Conclusion: Our findings show that automated analysis significantly overestimates ECD in the eyes with high polymegathism and/or large cell size, compared to the manual method. Therefore, we discourage reliance upon the fully-automated method alone to perform specular microscopy analysis, particularly if an accurate ECD value is imperative

Objetivo: Determinar la fiabilidad de la densidad celular endotelial corneal (ECD) obtenida mediante microscopio especular automático frente a métodos manuales validados y factores predictivos de la fiabilidad. Métodos: Se capturaron imágenes nítidas de 94 controles y 106 ojos glaucomatosos con un microscopio especular Konan NSP-9900. Todas las imágenes fueron analizadas por examinadores expertos mediante el software Konan CellChek, utilizando los métodos automatizado total, semiautomático y de centrado. Se compararon las imágenes con bajo recuento celular (número de células <100) y/o córnea guttata con el método de centrado y centrado flexible. Se compararon las ECD, utilizándose el error absoluto para valorar la variación. Se evaluó el efecto de la ECD sobre la edad, el recuento celular, el tamaño celular y la variación del tamaño celular. Resultados: No se observó diferencia significativa entre los métodos de centrado y centrado flexible en las córneas con guttata (p = 0,48) o baja ECD (p = 0,11). No se observó diferencia (p = 0,32) en cuanto a ECD en los controles normales < 40 años entre el método totalmente automatizado y el método de centrado manual. Sin embargo, en los controles mayores y en los ojos glaucomatosos, la ECD fue sobreestimada por el método totalmente automatizado (p = 0,034) y el método semiautomático (p = 0,025), en comparación al método manual. Conclusión: Nuestros hallazgos muestran que los análisis automatizados sobreestiman considerablemente la ECD en los ojos con alto polimegatismo y/o gran tamaño celular, en comparación al método manual. Por tanto, no recomendamos confiar en el método totalmente automatizado por sí solo para realizar estudios mediante microscopio especular, particularmente en casos en que la precisión del valor de ECD sea imperativo

Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática / Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review

Fundamento y objetivo: Las células T reguladoras circulantes podrían convertirse en un adecuado biomarcador para los trasplantados renales. El objetivo de este estudio es evaluar el efecto de los inhibidores de la mammalian target of rapamycin (I-mTOR, «diana de rapamicina en células de mamífero») en las células reguladoras, y el interés clínico de este efecto. Material y métodos: Revisión sistemática de trabajos publicados y no publicados. Bases de datos y repositorios del mundo entero. Se buscaron ensayos controlados aleatorizados y estudios de cohortes que compararon recuentos de células reguladoras y episodios de rechazo entre trasplantados tratados con y sin I-mTOR. Los trabajos podían medir la correlación células reguladoras-filtrado glomerular. Se evaluó la codependencia células reguladoras-eficacia de los I-mTOR. Resultados: Se incluyeron 5 ensayos y 9 estudios. Las diferencias clínicas no permitieron una estimación cuantitativa del efecto de la inmunosupresión en el número de células reguladoras. Sin embargo, observamos que hay más células reguladoras con sirolimus o everolimus. El número de episodios de rechazo fue similar con anticalcineurínicos que con I-mTOR, a pesar de las diferencias en el número de células reguladoras. La correlación combinada células reguladoras-filtrado glomerular fue prospectivamente de 0,114, con un intervalo de confianza al 95% (IC 95%) de 0,062-0,406, y retrospectivamente, de 0,13 (IC 95% 0,0-0,361). Existen pruebas directas, aunque de bajo nivel (aleatorización estratificada por el biomarcador), respecto a la codependencia células reguladoras-eficacia de los I-mTOR. Conclusión: El número de células reguladoras puede asociarse a buenos resultados o desenlaces en los tratados con I-mTOR (eficacia antirrechazo), considerando la relación entre estas células y la función del injerto. Registro: PROSPERO (CRD42016046285) (AU)

Background and objective: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. Material and methods: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. Results: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. Conclusions: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function Registration: PROSPERO (CRD42016046285) (AU)

Comportamiento de las células nucleadas en los distintos tipos de derrame pleural / Behaviour of nucleated cells in various types of pleural effusion

Introducción. El conocimiento del comportamiento de los componentes celulares del líquido pleural puede ayudar a enfocar el diagnóstico diferencial de un derrame pleural. El objetivo es evaluar su composición en los distintos tipos de derrames y valorar si proporciona información clínica relevante. Pacientes y métodos. Estudio observacional, transversal y retrospectivo en el que se analiza el componente celular de derrames pleurales de diversa etiología. Los derrames se clasificaron como neutrofílicos, linfocíticos (≥50% de cada uno de ellos), eosinofílicos (≥10%) o mesoteliales (>5%) y se agruparon en 6 categorías diagnósticas. Resultados. Se estudiaron 1.467 pacientes (354 insuficiencia cardiaca; 59 otros trasudados; 349 paraneumónicos; 133 tuberculosos; 397 neoplásicos y 175 otros exudados). El predominio celular fue linfocítico en la insuficiencia cardiaca (44,4%), paraneumónicos no complicados (29,2%), tuberculosis (88%) y neoplasias (49,6%); neutrofílico en los paraneumónicos (57%) y neoplásicos (9,6%); eosinofílico en las neoplasias (6,3%) y mesotelial en las tuberculosis (12%). Las etiologías más frecuentes con un recuento linfocitario ≥80% fueron tuberculosis (35,1%) y neoplasias (23,3%). Los parámetros con mayor capacidad discriminante fueron: leucocitos (trasudados: AUC 0,835) y porcentaje de neutrófilos (empiemas: AUC 0,906 y paraneumónicos complicados + empiemas: AUC 0,907). Conclusiones. Los recuentos de células nucleadas ayudan a enfocar la etiología del derrame pleural, ya que cada etiología suele tener un predominio celular característico. El porcentaje de células nucleadas en el líquido pleural no puede descartar tuberculosis si existe un recuento elevado de células mesoteliales, ni un derrame paraneumónico ante un predominio linfocítico, o malignidad con un recuento de linfocitos ≥80% (AU)

Introduction. To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. Patients and methods. Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories. Results. 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). Conclusions. Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes (AU)

Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions / Examen del frotis citológico y bloque celular del líquido pleural: valor diagnóstico complementario en los derrames malignos

Objectives. To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. Patients and methods. A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. Results. The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. Conclusions. If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used (AU)

Objetivos. Evaluar la utilidad independiente de frotis y bloques celulares (BC) del líquido pleural para diagnosticar derrames malignos. Pacientes y métodos. Se evaluaron retrospectivamente un total de 632 frotis citológicos y 554 BC de 414 pacientes consecutivos con derrame pleural maligno. Resultados. La sensibilidad diagnóstica de una primera muestra fue del 44%, tanto en frotis como en BC. El análisis de muestras separadas ulteriores aumentó al 56% la identificación de derrames malignos. Globalmente, el 11% de muestras negativas mediante frotis mostraron células malignas en los BC, mientras que el 15% de BC negativos resultaron positivos en el estudio del frotis. Los líquidos pleurales con recuentos bajos de hematíes o leucocitos produjeron con mayor frecuencia BC insuficientes para diagnóstico. Conclusiones. Si se evalúan frotis y BC, el porcentaje de resultados positivos es superior que si se emplean estas técnicas de forma aislada (AU)

¿Tiene utilidad el recuento cellular en el cáncer de colon? / In the cell count useful in colon cáncer?

Introducción: Proponemos valorar la utilidad del recuento celular en el cáncer de colon en nuestro medio. Material y Métodos. Realizamos un estudio observacional, analítico, longitudinal y retrospectivo, basado en un esquema de cohortes. Se reclutan a 47 pacientes intervenidos de cáncer de colon en 2015. Se establecieron dos grupos según estadio anato-mopatológico final (grupo 1: estadios 0 y I y grupo 2: estadios II, III y IV) y se recogen sus datos analíticos en distintos momentos. Con los recuentos celulares se calcularon las curvas ROC para varias ratios, para establecer el punto de corte a partir del cual la probabilidad de pertenecer al grupo 1 es más alta. Se forman dos grupos, A y B, según sus valores de ratio y tomando el punto de corte para dividirlos y se comparan factores anatomopatológicos de mal pronóstico, datos quirúrgicos y clínicos. Se describe también el valor de la NLR en pacientes con mala evolución de la enfermedad. Resultados: No encontramos diferencias estadísticamente significativas en la evolución de ambos grupos, A y B, tampoco en cuanto a su relación con factores de mal pronóstico anatomopatológicos o clínicos. Se realiza también un seguimiento de los valores del NLR en pacientes que presentaron recidiva o metástasis, exponiendo resultados descriptivos. Conclusiones. Se trata de una medida sencilla de determinar, por lo que a pesar de no haber encontrado diferencias significativas, valoramos su utilidad cómo elemento informativo y consideramos su interés en demostrar la significancia estadística aumentando tamaño muestral y periodo de seguimiento en trabajos posteriores

Introduction. We propose to evaluate the utility of cell counts in colon cancer in our environment. Material and Methods. We conducted an observational, analytical, longitudinal and retrospective study, based on a cohort scheme. 47 patients were recruited who underwent colon cancer in 2015. Two groups were established according to the final anato-mopathological stage (group 1: stages 0 and I and group 2: stages II, III and IV) and their analytical data were collected at different times. With the cell counts the ROC curves were calculated for several ratios, to establish the cut-off point from which the probability of belonging to group 1 is higher. Two groups are formed, A and B, according to their ratio values and taking the cut-off point to divide them and comparing anatomopathological factors of poor prognosis, surgical and clinical data. The value of the NLR is also described in patients with poor evolution of the disease. Results. We did not find statistically significant differences in the evolution of both groups, A and B, neither in relation to their relationship with poor pathological or clinical prognostic factors. The NLR values were also monitored in patients with recurrence or metastasis, with descriptive results. Conclusions. This is a simple measure to determine, so despite not having found significant differences, we value its usefulness as an informative element and we consider its interest in demonstrating statistical significance by increasing sample size and follow-up period in subsequent studies

Magnitudes biológicas que tiene interés medir de modo urgente / Biological markers in emergency laboratory

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Citotoxicidad del 1-O-undecilglicerol sobre células de mama humanas mediante análisis de células en tiempo real / Cytotoxicity of 1-O-undecylglycerol in human breast cells by Real Time Cell Analysis

Objetivos: Estudiar el efecto del 1-O-undecilglicerol sobre la proliferación de células de cáncer de mama MCF-7 y de mama normales 184B5. Métodos: Se realizó seguimiento a tiempo real de la viabilidad de ambas líneas celulares, con empleo del analizador de células en tiempo real. Se determinó la densidad celular apropiada para el estudio, y se trataron las células con dos concentraciones de 1-O-undecilglicerol durante 48 horas. Se compararon las pendientes del índice celular en cada experimento. Resultados: El 1-O-undecilglicerol redujo significativamente la proliferación de las células MCF-7, mientras que fue poco citotóxico sobre las células 184B5 hasta 75μM. A la concentración de 150μM fue citotóxico para ambas líneas, pero invirtió la pendiente del índice celular de las células de cáncer de mama. Conclusiones: El 1-O-undecilglicerol podría ser candidato para futuros estudios en modelos in vivo de cáncer de mama, así como para la profundización en el mecanismo involucrado en este efecto

Aim: To study the effect of 1-O-undecylglycerol on the proliferation of human breast cancer cells MCF-7 and 184B5 normal breast cells. Methods: Real time following of both cell lines was performed, by Real Time Cell Analyzer. Appropriated cell density was selected, and cells were treated with two concentrations of 1-O-undecylglycerol for 48 hours. Cell index slopes were compared in each experiment. Results: 1-O-undecylglycerol induced significant reduction of MCF-7 cell viability, and was less cytotoxic on 184B5 cells with 75μM. At 150μM was cytotoxic for both lines, but cell index slope of breast cancer cells was negative. Conclusion: 1-O-undecilglicerol could be a candidate for future studies in in vivo models of breast cancer, and for further experiments about the mechanism involved in this effect

Utilidad del esputo inducido en la práctica clínica habitual / Utility of Induced Sputum in Routine Clinical Practice

Objetivos: Determinar la utilidad general y específica (diagnóstica y/o terapéutica) del recuento de las células inflamatorias (RCI) del esputo inducido (EI) en situación de asistencia clínica real. Métodos: Estudio retrospectivo que incluyó a los 171 pacientes que durante un año se les recogió un EI para determinar su RCI en un servicio de Neumología de un hospital de referencia. Observadores independientes al equipo médico habitual establecieron si la información proporcionada por el RCI del EI fue útil en la toma de decisiones diagnósticas y terapéuticas. Resultados: Las causas más frecuentes que motivaron la solicitud del RCI del EI fueron: asma 103 (59,20%); asma de control difícil 34 (19,54%); tos crónica 19 (10,9%), y reflujo gastroesofágico 15 (8,6%). En 115 (67,3%) pacientes el RCI del EI resultó clínicamente útil (valoración general); en 98 (57,3%) proporcionó información diagnóstica, y en 85 (49,7%), información terapéutica relevante. En el asma, asma de control difícil, tos crónica y reflujo gastroesofágico fue útil en el 71,8, el 67,6, el 47,4 y el 60%, respectivamente. Conclusiones: La información proporcionada por el RCI del EI resulta de gran utilidad en la práctica clínica, particularmente en el asma y la tos crónica. Estos resultados podrían proporcionar argumentos para recomendar la incorporación de la técnica en los servicios de Neumología de referencia y en las unidades de excelencia de asma)

Objective: To determine the general and specific utility in diagnosis and/or treatment of induced sputum (IS) inflammatory cell counts in routine clinical practice. Methods: Retrospective study of 171 patients referred for clinical sputum induction over a 1-year period in the pulmonology department of a referral hospital. Independent observers established whether the information provided by IS inflammatory cell count was useful for making diagnostic and therapeutic decisions. Results: The most frequent reasons for determination of IS inflammatory cell count were: asthma 103 (59.20%); uncontrolled asthma 34 (19.54%); chronic cough 19 (10.9%), and gastroesophageal reflux 15 (8.6%). In 115 patients (67.3%) it was generally useful for diagnosis and/or treatment; in 98 patients (57.3%) it provided diagnostic information and in 85 patients (49.7%) it assisted in therapeutic decision-making. In asthma, uncontrolled asthma, chronic cough and gastroesophageal reflux, the results were useful in 71.8%, 67.6%, 47.4% and 60%, respectively. Conclusion: The information provided by IS inflammatory cell count is extremely useful in clinical practice, especially in asthma and chronic cough. These results may justify the inclusion of the IS technique in pulmonology departments and asthma units of referral centers

Factores histopatológicos con valor pronóstico en el cordoma sacro. Estudio de 10 casos del Hospital Universitario Doctor Peset y el Hospital Clínico Universitario de Valencia / Histopathological factors of prognositic value in sacral chordoma. A 10 case study from the University Hospital «Doctor Peset» and the University Clinical Hospital of Valencia

El cordoma es una neoplasia de la línea media espinal que tiene su origen en derivados normales o en remanentes de la notocorda. Representa entre 1 y 4% de todos los tumores de hueso y suele afectar los extremos del esqueleto axial. Se considera una neoplasia de bajo grado con crecimiento lento e infrecuentes metástasis, sin embargo su gran capacidad de invasión local y su alto índice de recurrencia causan una considerable mortalidad tardía. Varios autores han propuesto múltiples factores clínicos y biológicos para predecir el pronóstico de la enfermedad, sin embargo la utilidad de la evaluación histopatológica pronóstica no está aún bien definida en estos casos. El objetivo de este estudio es evaluar las características histopatológicas de 10 casos de cordomas y correlacionar dichos datos con la evolución de la enfermedad (AU)

Chordomas are rare midline neoplasms arising from notochord tissue remnants. They account for 1-4% of all bone malignancies. Although considered to be slow growing, low grade neoplasms which rarely metastasize, their tendency for local invasion and frequent recurrence mean that they have a considerable late mortality rate. Several clinical and biological factors have been proposed as prognostic indicators, however, histopathological characteristics have not yet been considered. Our aim is to evaluate the histopathological features of ten cases of chordoma in relation to the clinical outcome (AU)

¿Es útil la reevaluación de cristales en el líquido sinovial? / Reassessment of crystals in synovial fluid: is it helpful?

Introducción. El recuento celular, el análisis de cristales y el estudio microbiológico del líquido sinovial (LS), son piezas claves en el diagnóstico y manejo del derrame articular pues conducen a decisiones clínicas y terapéuticas. El análisis de cristales suele realizarse en campo claro y con luz polarizada compensada (LPC). Depende de la experiencia del examinador y del número de cristales presentes. Para aumentar el rendimiento, se puede analizar el sedimento tras centrifugación. Hay autores que sugieren que la maduración in vitro de los cristales facilita su identificación tras 24 horas de la extracción. Otros sugieren que dicha demora deteriora la muestra. Nuestro objetivo es valorar si el re-examen del LS a las 24 horas puede aumentar el rendimiento diagnóstico para cristales. Material y métodos. Se analizaron durante 4 meses las muestras de LS remitidas para su análisis con LP y microscopía de campo claro; se realizó reevaluación a las 24 horas en todos los casos posibles. Resultados. Recibimos 174 LS, de los cuales 138 (79,3%) fueron negativos para el primer análisis y 36 positivos. En 84 casos (60,8%) se pudo realizar una evaluación a las 24 horas. En 10 casos (11,9%) se observaron cristales que no habían sido vistos en el primer análisis. Siempre se trató de cristales de pirofosfato cálcico dihidratado. El incremento de muestras positivas tras el segundo examen fue de un 27,8% (IC 95%: 13,1-42,4). Conclusión. El reanálisis de cristales en LS a las 24 horas debe considerarse en los casos de sospecha de artropatía microcristalina con primer examen negativo (AU)

Background. White blood cell counts, analysis of crystals in synovial fluid (SF) and microbiological studies are key measurements in the diagnosis and management of joint effusion. The results may lead to clinical and therapeutic decisions. The diagnosis of crystals in SF, usually performed by examination with compensated polarised light microscopy (PL), is not easy. It depends on the experience of the examiner and amount of crystals in the sample, which is sometimes very small. In order to increase the performance, analysis may be performed on the sediment after centrifugation. Some authors suggest that due to in vitro maturation of crystals, they can be more easily identified 24hours after extraction. Others suggest that the sample deteriorates. We question whether re-examination of SF can increase the diagnostic yield of this test. Methods. Over a 4 month period we analysed crystals in SF received in the laboratory using a PL and ordinary light microscopy. Where this was possible, the SF was examined again after 24hours. Results. We received 174 SF; 138 (79.3%) were negative for the first analysis. In 84 cases (60.8%) a re-evaluation could be made after 24hours by trained staff. In 10 cases (11.9%) crystals that had not been seen previously became apparent. In all cases they were calcium pyrophosphate dihydrate crystals. The number of positive fluids increased by 27.8% (95% CI: 13.1-42.4) after a second assay. Conclusions. The re-analysis of crystals in SF at 24hours should be considered in cases of high suspicion of microcrystalline arthropathy when the first test is negative (AU)

Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival

INTRODUCTION: Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer. MATERIAL AND METHODS: One hundred and five resected specimens were used. The level of tumour hypoxia was evaluated using (31)P NMR spectroscopy, CD68 (tumour-associated macrophages), CD34 (microvessel density, MVD) and VEGF expression, immunohistochemistry, MMP-2 and MMP-9 activity, zymography. Statistical analysis was conducted using Pearson's test, Kaplan-Meier survival analysis, log-rank test and Cox proportional hazards model. RESULTS: Intratumoral hypoxia level has been significantly correlated with VEGF expression, TAM number and total protease activity. The overall survival rate of patients with strong tumour hypoxia, high level of MVD, VEGF expression, TAM and MMP activity was significantly lower than that of the patients without the mentioned tumour characteristics. CONCLUSIONS: The hypoxia-associated signalling that is activated in tumours promotes tumour progression through the recruitment of macrophages, remodelling of extracellular matrix and neoangiogenesi (AU)

Células de Langerhans CD1a+ en la epidermis peritumoral del carcinoma basocelular / CD1a+ Langerhans Cells in the Peritumoral Epidermis of Basal Cell Carcinoma

Introducción. El carcinoma basocelular (CBC) es un tumor maligno frecuente y su incidencia ha aumentado en las últimas décadas. Investigaciones han demostrado la relación entre radiación ultravioleta (RUV), sistema inmune cutáneo y CBC. La función de las células de Langerhans (CL) en la respuesta inmune antitumoral ha motivado la investigación de su densidad y morfología frente a la RUV y al CBC. Sin embargo, los resultados publicados presentan discordancias debido a diferencias en la metodología científica. Objetivo. Estudiar la densidad y morfología de las CL en la epidermis peritumoral comparada con la epidermis supratumoral mediante inmunohistoquímica y un programa computacional de imágenes digitales. Material y métodos. Doce casos de CBC fueron teñidos con CD1a. Se utilizó microscopia óptica y el programa computacional Image J para calcular las áreas epidérmicas sobre el tumor y adyacente a él. Se contabilizaron el número de CL de cada área y se determinaron y compararon las densidades celulares. Finalmente, se analizó la morfología de las CL en ambas áreas epidérmicas. Resultados. Los resultados mostraron una menor densidad celular en la epidermis supratumoral respecto a la peritumoral (p < 0,05). Las CL entre ambas áreas presentaron diferencias en el tamaño, forma celular y patrón dendrítico. Discusión. La menor densidad y alteraciones estructurales de las CL supratumorales podrían dar lugar a variaciones de la respuesta inmune en el CBC. El uso de tecnología de análisis de imágenes digitales sería un método fiable en el estudio morfométrico de las CL (AU)

Background. Basal cell carcinoma (BCC) is a common malignant tumor and its incidence has risen in recent decades. Research has shown the relationship between ultraviolet (UV) radiation, the skin immune system, and BCC. The role of Langerhans cells (LC) in the immune response to tumors has prompted research into LC density and morphology in response to UV radiation and BCC. However, the data are inconsistent due to differences in research methodology. Objective. To study the density and morphology of LCs in the peritumoral epidermis of BCC using immunohistochemistry and image processing software and compare the results with those from the epidermis overlying the tumor. Material and methods. Twelve samples from patients with BCC were prepared with a CD1a stain. Areas of epidermis overlying and adjacent to the tumor were defined using light microscopy and the Image J image processing software. The LCs in each area were counted and the cell densities were calculated and compared. Morphological features of LCs were also evaluated in each epidermal areas. Results. The results showed a lower density of LCs in the epidermis overlying the tumor than in the peritumoral epidermis (p < 0.05). There were also differences in the size, shape, and dendritic pattern of the LCs between the epidermal areas. Conclusions. The lower density and fewer morphological changes of LCs in the epidermis overlying BCC may give rise to alterations in the immune response to BCC. Digital image analysis is a reliable method for the morphometric evaluation of LCs (AU)