Relationship between commonly defined metabolic health phenotypes and obesity with lung function in a working population: A cross-sectional study.

BACKGROUND: Four phenotypes relate metabolism and obesity: metabolically healthy (MHO) and unhealthy (MUO) people with obesity and metabolically healthy (MHNO) and unhealthy (MUNO) people without obesity. No studies have addressed the association between these categories and lung function in the working population. OBJECTIVES: The aim was to determine the relationship of phenotypes to lung ageing as measured by lung age and its relationship to lung dysfunction. METHODS: A descriptive cross-sectional study was conducted in a working population. The outcome variable was lung function assessed by lung age. The four phenotypes of obesity and metabolic health (MHNO, MHO, MUO and MUNO) were determined using NCEP-ATP III criteria. Lung dysfunctions were classified into restrictive, obstructive, and mixed patterns. RESULTS: The mean age of the participants was 43.7 years, ranging from 18 to 67 years. Of the 1860 workers, 51.3 % were women. The prevalences found were 71.4 %, 12 %, 10.6 % and 6 % for MHNO, MUO, MHO, and MUNO, respectively. MHO (ß = 0.66; p = 0.591) was not associated with increased lung ageing compared with MHNO, but MUO (ß = 7.1; p < 0.001) and MUNO (ß = 6.6; p < 0.001) were. Concerning pulmonary dysfunctions, MUNO (OR = 1.93; p < 0.001) and MUO (OR = 2.91; p < 0.001) were found to be related to the presence of a restrictive pattern, and MUNO (OR = 2.40; p = 0.028) to the mixed pattern. CONCLUSION: The results show that metabolic abnormalities, not obesity, are responsible for premature lung ageing and, therefore, lung function decline. In our study, having obesity without metabolic abnormality was not significantly associated with the presence of dysfunctional respiratory patterns.

Phase II Trial Evaluating Olaparib Maintenance in Patients with Metastatic Castration-Resistant Prostate Cancer Responsive or Stabilized on Docetaxel Treatment: SOGUG-IMANOL Study.

The SOGUG-IMANOL trial was a phase 2, uncontrolled, Spanish multicenter study to assess the effect of maintenance treatment with olaparib on radiographic progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who achieved partial or complete response or disease stabilization on docetaxel treatment and had a documented germline/somatic mutation in any of the homologous recombination repair (HRR) genes. Patients received olaparib 300 mg orally twice daily. From the screened population (n = 134), 26 (19.4%) somatic mutations were found, and 14 patients were included in the study. The median radiographic PFS was 11.1 (95%CI, 5.7 to 16.5) months. The median PSA-PFS was 3.5 (95%CI, 1.0 to 6.0) months, and the median clinical PFS was 14.7 (95%CI, 1.8 to 27.5 months). Clinical benefit was observed in 12 patients (85.7%, 95%CI 67.4% to 100%), including two patients with partial response and 10 with stable disease. Six patients reported grade 3-5 adverse events: asthenia (n = 3), anemia (n = 2) and neutropenia (n = 1). In this setting, olaparib has been shown to be an efficacious maintenance treatment in terms of radiographic PFS and clinical benefit, becoming a therapeutic option for some patients harboring an HRR gene mutation and in scenarios where further investigation is needed.

The Impact of Metabolic Syndrome Risk Factors on Lung Function Impairment: Cross-Sectional Study.

BACKGROUND: Metabolic syndrome (MetS) is a constellation of risk factors increasingly present in the world's population. People with this syndrome are at an increased risk of cardiovascular disease and type 2 diabetes mellitus. Moreover, evidence has shown that it affects different organs. MetS and its risk factors are independently associated with impaired lung function, which can be quantified through spirometric variables. OBJECTIVE: This study aims to determine whether a high number of MetS criteria is associated with increased lung function decline. METHODS: We conducted a descriptive cross-sectional study with a random sample of 1980 workers. Workers with acute respiratory pathology (eg, influenza), chronic respiratory pathology (eg, chronic bronchitis), or exposure to substances harmful to the lungs (eg, organic and inorganic dust) were not included. MetS was established based on harmonized criteria, and lung function was assessed according to spirometric variables. On the basis of these, classification into restrictive lung disease (RLD), obstructive lung disease, and mixed lung disease (MLD) was performed. In addition, the association between MetS and lung function was established based on analysis of covariance, linear trend analysis, and multiple linear regression. RESULTS: MetS was associated with worse lung function according to all the spirometric parameters analyzed (percentage of predicted forced expiratory volume in 1 second: mean 83, SD 13.8 vs mean 89.2, SD 12.8; P<.001 and percentage of predicted forced vital capacity: mean 85.9, SD 11.6 vs mean 92, SD 11.3; P<.001). Moreover, those diagnosed with MetS had a higher prevalence of lung dysfunction (41% vs 21.9%; P<.001), RLD (23.4% vs 11.2%; P<.001), and MLD (7.3% vs 2.2%; P<.001). Furthermore, an increasing number of MetS criteria was associated with a greater impairment of pulmonary mechanics (P<.001). Similarly, with an increasing number of MetS criteria, there was a significant linear trend (P<.001) in the growth of the prevalence ratio of RLD (0 criteria: 1, 1: 1.46, 2: 1.52, 3: 2.53, 4: 2.97, and 5: 5.34) and MLD (0 criteria: 1, 1: 2.68, 2: 6.18, 3: 9.69, and 4: 11.37). Regression analysis showed that the alteration of all MetS risk factors, adjusted for various explanatory variables, was significantly associated with a worsening of spirometric parameters, except for forced expiratory volume in 1 second/forced vital capacity. CONCLUSIONS: The findings have shown that an increase in cardiometabolic risk factors is associated with a more significant worsening of spirometric variables and a higher prevalence of RLD and MLD. As spirometry could be a crucial tool for monitoring patients at risk of developing chronic pathologies, we conclude that this inexpensive and easily accessible test could help detect changes in lung function in patients with cardiometabolic disorders. This highlights the need to consider the importance of cardiometabolic health in lung function when formulating public health policies.

Diagnostic accuracy of the waist-to-height ratio and other anthropometric indices for metabolically healthy obesity in the working population.

Approximately one-third of overweight individuals, and half of those with obesity, do not have cardiometabolic disorders. For this reason, a phenotype called metabolically healthy obese (MHO) has emerged to describe this population group. The early detection of this situation could save costs associated with the development of comorbidities or pharmacological interventions. Therefore, the aim is to know the prevalence of MHO in the working population and propose variables for its detection. Cross-sectional descriptive study of 635 workers of the Cordoba City Council was carried out based on the results of the 2016 health surveillance. The outcome variables were the MHO, established based on the criteria of the IDF, NCEP-ATP III, and Aguilar-Salinas. In addition, the degree of agreement between the different MHO criteria was studied using Cohen's kappa (k), and the predictive capacity of the anthropometric variables was assessed with Receiver Operator Curves. The prevalence of MHO ranged from 6.6 to 9%. The highest agreement was reached between the IDF and NCEP-ATP III definitions (k = 0.811; 95% CI 0.724-0.898; p < 0.001). The waist-to-height ratio (WHtR) showed the highest discriminant capacity for MHO, with its best cut-off point at 0.55 for all criteria used. Sensitivity ranged from 84 to 93%. The prevalence of MHO in the working population differed according to the criteria used for diagnosis. The anthropometric variable with the highest discriminant capacity for MHO was WHtR, presenting the same cut-off point in the three criteria analyzed. Therefore, WHtR is the variable that best detects the presence of MHO.

Lifestyle, Type of Work, and Temporary Disability: An Incidence Study of the Working Population.

The objective of the study was to identify lifestyles associated with loss of health among workers. A retrospective longitudinal incidence study was carried out over a three-year period (2015, 2016, and 2017) among the working population. A total of 240 workers were analysed using information from occupational health assessments. The outcome variable was loss of health due to common illness or workplace injury, quantified by the number of days each episode lasted. Predictor variables were age, gender, type of work, tobacco use, alcohol consumption, physical activity (IPAQ), and adherence to the Mediterranean diet (AMD). An adjusted multiple linear regression was performed, determining the goodness of fit of the final model using the coefficient of determination adjusted r2. During the study, 104 men (58.8%) and 25 women (39.7%) suffered an episode of illness or workplace injury (p < 0.05). The overall incidence was 17.9% people/year 95% CI [15, 21.3]. 4.6% of the workers were sedentary or engaged in light physical activity, and 59.2% maintained an adequate AMD. Workers who engaged in high levels of physical activity had an average of 36.3 days of temporary disability compared to 64.4 days for workers with low-moderate levels of physical activity (p < 0.01).

Molecular Biomarkers of Prognosis in Advanced Renal Cell Carcinoma Patients Treated With Pazopanib Plus Interferon Alpha (INF-2A) in a Phase I/II Study by the Spanish Oncology Genitourinary Group.

INTRODUCTION: The therapeutic repertoire available for advanced renal cell carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy, required for molecular biomarkers for response. PATIENTS AND METHODS: This was a phase I to II trial on the combination of pazopanib with interferon-alpha (INF-2A) as first-line treatment for advanced RCC. The primary endpoint was recommended phase II dose (RP2D) and efficacy in terms of objective response rate (ORR, RECIST 1.1 criteria). Secondary endpoints included safety and a translational study of molecular biomarkers in serum and exosomes from peripheral blood samples at three-time points: baseline, 8 weeks of treatment, and progression of the disease. RESULTS: Between July 2011 and July 2017, 53 eligible patients were treated and followed up (I, n = 20; II, n = 33). Pazopanib 800 mg + INF-2A 3 MIUs showed a manageable safety profile; therefore, it was selected for dose expansion. Overall, grade 3/4 toxicities were reported in 24 (72.7%) patients. The ORR was 27.2%. The 12-month OS rate was 83.6% (median not reached), and after 30.9 months of follow-up, 24 (72.7%) patients were still alive. CCL2, IL8, TNF-α, and PD-L1 were significantly overexpressed after treatment initiation, while TGF-ß1 and CCL5 were significantly decreased. TNF-α, endoglin, and PD-L1 expression are correlated with the response after treatment initiation. CONCLUSION: The trial did not reach its pre-specified target ORR. However, OS was longer than expected with pazopanib monotherapy. Changes in the molecular profile suggest a crucial role of vascular remodeling and inflammatory-mediated immune cell infiltration in optimal response to pazopanib plus INF-2A.

Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial.

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors. Pathways connected to tissue growth and angiogenesis might have been associated with reduced survival benefit. Individual biomarkers did not comprehensively identify patients who could benefit from therapy; however, multi-parameter models incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility. These results characterize the complex biologic pathways underlying survival benefit from immune checkpoint inhibition in advanced urothelial cancer and suggest that multiple biomarkers might be needed to identify patients who would benefit from treatment.

Adherence to the Mediterranean diet according to occupation-based social classifications and gender.

BACKGROUND: The link between the dietary pattern known as the Mediterranean diet (MedDiet) and lower morbidity/mortality is well known, and its efficacy in the primary prevention of cardiovascular diseases has been proven in recent years. However, adherence to the MedDiet seems to be related to socioeconomic status. The objective was to analyze whether their adherence to the MedDiet differs from the rest of the working population. Material and methods: A transversal study was carried out on adherence to the MedDiet. One thousand six hundred nine workers were studied, of whom 626 belonged to the group of workers at risk of social exclusion. Results: It was found that 43.9% of the permanent staff had a high adherence, compared to the figure of 20.9% for the population at risk of exclusion (p < .01). No differences were evident between men and women in the same category of workers (41.7% vs. 47.9% in permanent staff and 22.5% vs. 40.5% in workers at risk of social exclusion). The lowest adherence to the MedDiet (11.4%) was found in the group of young women at risk of social exclusion. Their consumption of healthy foods was significantly lower than the group of older women, while their consumption of less healthy foods (cakes/pastries, butter and fizzy drinks) was higher. Conclusions: It is difficult to draw conclusions about whether it is the most expensive foods contained in the MedDiet which cause this difference in adherence, since, there is also a higher expenditure on non-essential products such as cakes/pastries, fizzy drinks and tobacco. Key messagesPeople at risk of social exclusion and specially the younger women have a lower adherence to the Mediterranean diet than other occupational social classes.The higher consumption of butter, fizzy drinks and cakes/pastries is the dietary habit which most affects adherence to the Mediterranean diet in the group of people at risk of exclusion.It is not possible to ensure that the higher cost of any foods included in the Mediterranean diet, such as fish and fruit, is the main cause of this difference in adherence.

[Comparison of classic and new anthropometric indexes for the screening of metabolic syndrome on the working population.] / Comparación de índices antropométricos, clásicos y nuevos, para el cribado de Síndrome Metabólico en población adulta laboral.

OBJECTIVE: Metabolic syndrome (MetS) has become a worldwide epidemy as the result of a high prevalence of obesity and a sedentary lifestyle. This study was aimed to determine the predictive capacity of some anthropometric indexes on the metabolic syndrome MetS. METHODS: A cross-sectional study was carried out in 636 workers with an overall prevalence of MetS of 14.3%. Receiver Operating Characteristic curves have been carried out to determine the cut-off values. Diagnostic accuracy was determined from the sensitivity and specificity, predictive values, validity index, and Youden index. RESULTS: Waist-to-Height Ratio (WHtR) and Body Round Index (BRI) were the variables with the highest area under the curve (AUC) both with 0.89 CI 95% (0.858-0.927), followed by Waist Circumference with 0.87 CI 95% (0.83-0.909). The most outstanding cut-off values were: WtHR (0.54), with a sensitivity of 90.1% and a specificity of 76.1% and BRI (4.15) achieved a sensitivity and specificity of 90.1% and 76.1%, respectively. CONCLUSIONS: WHtR and BRI are the anthropometric indicators that best discriminate the incidence and prevalence of MetS on the working population. In addition, they show a significant discriminatory capability of abdominal obesity.

OBJETIVO: El síndrome metabólico (SMet) se ha convertido en una epidemia a nivel mundial, como resultado de una alta prevalencia de obesidad y de un estilo de vida sedentario. El objetivo de este trabajo fue determinar la capacidad predictiva de los índices antropométricos sobre el SMet. METODOS: Se realizó un estudio transversal en una muestra de 636 trabajadores, con una prevalencia global de SMet del 14,3%. Se realizaron Curvas Operador-Receptor para determinar los valores de corte. La precisión diagnóstica se determinó a partir de la sensibilidad y especificidad, los valores predictivos, el índice de validez y el índice de Youden. RESULTADOS: Las variables con mayor área bajo la curva (ABC) fueron el índice cintura-talla (ICT) y el índice de redondez del cuerpo (BRI) con 0,89 (IC 95% 0,858-0,927), seguidos de la circunferencia de cintura (CC) con 0,87 (IC 95% 0,83-0,909). Los valores de corte fueron: ICT=0,54, con una sensibilidad del 90,1% y una especificidad del 76,1%; BRI=4,15, con una sensibilidad y especificidad del 90,1% y 76,1%, respectivamente. CONCLUSIONES: El ICT y el BRI son los indicadores antropométricos que mejor discriminan la incidencia y prevalencia de SMet en población adulta laboral. Además, muestran una importante capacidad discriminatoria de obesidad abdominal.

Waist to Height Ratio and Metabolic Syndrome as lung dysfunction predictors.

Metabolic Syndrome (MetS) has been related to pulmonary diseases but its relationship with lung age has not been sufficiently studied. In addition, anthropometric variables have been associated with pulmonary dysfunction, highlighting the waist-to-height ratio (WHtR). The aim was to evaluate the relationship between MetS and: lung age, anthropometric variables and the alteration of lung function. A cross-sectional study was carried out in 1901 workers, evaluating lung function through lung age (Morris & Temple equation) and spirometric values. The diagnosis of MetS was based on the harmonized criteria. We measured anthropometric variables (WHtR, waist circumference, body mass index, waist to hip ratio), blood pressure and biochemical variables (glucose, cholesterol total, HDL, triglycerides). Workers suffering from MetS showed an accelerated lung aging (59.4 ± 18.7 years vs 49 ± 18.4 years). The WHtR ≥ 0.55 was significantly related to an increase in lung age (ß = 6.393, p < 0.001). In addition, a significant linear trend was found between clinical categories of WHtR and lung dysfunction, restrictive and mixed pattern. MetS caused an accelerated lung aging and favored the presence of restrictive lung impairment. In addition, WHtR ≥ 0.55 has been shown as the best predictor for pulmonary health.

[Incidence of ischemic heart disease and stroke in workers of a local administration in southern Spain over ten years of follow-up]. / Incidencia de cardiopatía isquémica y accidente cerebrovascular en trabajadores de una administración local del sur de España a lo largo de diez años de seguimiento.

OBJECTIVE: Cardiovascular disease is the first cause of death in Spain. There are a few studies about the incidence of ischemic heart disease and cerebrovascular disease in workers. The objectives of this study were to determine the incidence of coronary and cerebrovascular disease in a cohort of workers of a public administration in the south of Spain, to estimate the prevalence of CVRF and its contribution to it, as well as to evaluate the predictive behavior of the REGICOR function. METHODS: Longitudinal historical cohort study, not concurrent, consisting of 698 workers, recruited from occupational health examinations. The dependent variables were the appearance of CI or CVD while leading independent were glucose, cholesterol, triglycerides, BMI, blood pressure, waist circumference, physical activity, smoking and REGICOR score and Score. Is performed Cox regression and its calculated area AUC of the ROC curve area for the explanatory variables. RESULTS: According to the REGICOR function, 0.6% of the population was classified as high risk. The Incidence Density per 100,000 persons-year for ischemic heart disease in women was found to be 53.9 by 357.4 in men, without significant differences with respect to those expected from the REGICOR function. The combined DI for ischemic heart disease and stroke was 477.1 per 100,000 person-years (men). CONCLUSIONS: The REGICOR function adequately assesses cardiovascular risk globally, losing predictive capacity according to risk groups. Smoking and blood pressure are shown as modifiable risk factors with greater independent association in the onset of cardiovascular disease.

OBJETIVO: Las enfermedades cardiovasculares son la primera causa de muerte en España. Existen escasos estudios sobre incidencia de acontecimientos cardiovasculares en trabajadores. Los objetivos de este trabajo fueron conocer la incidencia de cardiopatía isquémica (CI) y enfermedad cerebrovascular (ECV) en trabajadores de una administración pública del sur de España, estimar la prevalencia de los factores de riesgo cardiovascular (FRCV) y su contribución a la misma, así como evaluar el comportamiento predictivo de la función REGICOR. METODOS: Se realizó un estudio longitudinal de cohortes históricas, no concurrentes, constituidas por 698 trabajadores, reclutados en los exámenes de salud laboral. Las variables dependientes fueron la aparición de CI o ECV, mientras que las principales independientes fueron glucosa, colesterol, triglicéridos, Índice de Masa Corporal (IMC), presión arterial, perímetro abdominal, actividad física, tabaquismo y puntuación REGICOR. Se llevó a cabo una regresión de Cox y se calculó el área ABC de la curva ROC para las variables explicativas. RESULTADOS: Según la función REGICOR, se clasificó de alto riesgo al 0,6% de la población. La Densidad de Incidencia (DI) por cada 100.000 personas-año para cardiopatía isquémica en mujeres resultó ser de 53,9 por 357,4 en hombres, sin diferencias significativas respecto a las esperadas a partir de la función REGICOR. La DI combinada para cardiopatía isquémica y accidentes cerebrovasculares fue de 477,1 por cada 100.000 personas-año (en hombres). CONCLUSIONES: La función REGICOR valora adecuadamente el riesgo cardiovascular de manera global, perdiendo capacidad predictiva según grupos de riesgo. El tabaquismo y la presión arterial se muestran como los factores de riesgo modificables con mayor asociación independiente en la aparición de una enfermedad cardiovascular.

Equation Córdoba: A Simplified Method for Estimation of Body Fat (ECORE-BF).

BACKGROUND: Many methods for measuring body fat have been developed, but applications in clinical settings are limited. For this reason, researchers have tried to identify different formulas for its estimation but most of are hard to incorporate into daily work due to the variability in population and difficulty of use. The aim of this study was to develop and validate a new equation for the simplified estimation of body fat using the Clínica Universidad de Navarra - Body Adiposity Estimator (CUN-BAE) as a reference. METHODS: This research was conducted in two phases. In the first, the new body fat estimation equation was developed. The developed equation was validated in the second phase. Pearson's linear correlation, raw and adjusted linear regressions, the intraclass correlation coefficient, and Bland-Altman graphs were used. RESULTS: The variables that best adjusted the body fat percentage were age, sex, and the Napierian logarithm of Body Mass Index (LnBMI), forming the Equation Córdoba for Estimation of Body Fat (ECORE-BF) model. In its validation, the model presented correlation values of 0.994, an intraclass correlation coefficient of 0.960, with the Bland-Altman graph indicating means differences of 1.82 with respect to the estimation with the CUN-BAE. Nevertheless, although the aim was to simplify the CUN-BAE, the main limitation of this study is that a gold standard, such as air displacement plethysmography (ADP) or dual-energy X-ray absorptiometry (DXA), was not used. CONCLUSIONS: The proposed equation (ECORE-BF) simplified the CUN-BAE and provided a precise method, respecting the principle of parsimony, for the calculation of body fat.

[Workers especially sensitive to cardiovascular risk]. / Trabajadores especialmente sensibles al riesgo cardiovascular.

OBJECTIVE: Of the 607 fatal work accidents produced in Spain in 2016, 37.9% were due to ischemic heart disease and cerebral stroke. Working conditions such as night work, noise or respiratory pollutants are associated with higher cardiovascular incidence. The objective of the present study was to assess whether health surveillance in workers exposed to these conditions should include the assessment of cardiovascular risk. METHODS: Cross-sectional study of 680 workers in a public administration. The working conditions were obtained from the business risk assessment and the personal data that allowed the cardiovascular risk assessment, from the medical examination carried out in 2015. For the statistical analysis, Chi-square test (prevalence comparison) and Student's T test or Mann Whitney U test (means comparison), were applied. RESULTS: Exposed was 30.1%, showing significant differences by sex (37% men, 11.9% women, p<0.05). According to REGICOR, 13.2% of those exposed were particularly susceptible to cardiovascular risk. CONCLUSIONS: A large percentage of workers were exposed to CT related to a higher prevalence of cardiovascular pathology. The percentage of workers qualified as especially sensitive to cardiovascular risk among those exposed suggests that it should be assessed in the monitoring of occupational health when there are working conditions related to cardiovascular pathology.

OBJETIVO: De los 607 accidentes de trabajo mortales producidos en España en 2016, el 37,9% fueron por cardiopatía isquémica e ictus. Condiciones de trabajo como el trabajo nocturno, el ruido o los contaminantes respiratorios se asociaron a una mayor incidencia cardiovascular. El objetivo del presente trabajo fue valorar si la vigilancia de la salud en los trabajadores expuestos a esas condiciones debía incluir la valoración del riesgo cardiovascular. METODOS: Se realizó un estudio transversal en 680 trabajadores de una administración pública. La calificación de las condiciones de trabajo se obtuvo de la evaluación de riesgos empresarial y de los datos personales, antropométricos y analíticos, los cuales permitieron la valoración del riesgo cardiovascular en el reconocimiento médico realizado en 2015. Para el contraste estadístico, se aplicó la prueba de Chi-cuadrado para la compararación de prevalencias, y la prueba de T de Student o U de Mann-Whitney para la comparación de medias. RESULTADOS: Estuvieron expuestos a esas condiciones de trabajo el 30,1% de la muestra, observándose diferencias significativas por sexo (37% en los hombres, 11,9% en las mujeres, p<0,05). Según REGICOR, se calificó como especialmente sensibles a riesgo cardiovascular al 13,2% de los expuestos. CONCLUSIONES: Un amplio porcentaje de trabajadores está expuesto a CT relacionadas con mayor prevalencia de patología cardiovascular. El porcentaje de trabajadores calificados como especialmente sensibles al riesgo cardiovascular entre los expuestos aconseja que éste deba ser valorado en la vigilancia de la salud en el trabajo cuando existan condiciones de trabajo relacionadas con patología cardiovascular.

New Chondrosarcoma Cell Lines with Preserved Stem Cell Properties to Study the Genomic Drift During In Vitro/In Vivo Growth.

For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17). These lines displayed cancer stem cell-related and invasive features and were able to initiate subcutaneous and/or orthotopic animal models. Different mutations in Isocitrate Dehydrogenase-1 (IDH1), Isocitrate Dehydrogenase-2 (IDH2), and Tumor Supressor P53 (TP53) and deletion of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) were detected both in cell lines and tumor samples. In addition, other mutations in TP53 and the amplification of Mouse Double Minute 2 homolog (MDM2) arose during cell culture in CDS17 cells. Whole exome sequencing analysis of CDS17, T-CDS17, and matched patient samples confirmed that cell lines kept the most relevant mutations of the tumor, uncovered new mutations and revealed structural variants that emerged during in vitro/in vivo growth. Altogether, this work expanded the panel of clinically and genetically-annotated chondrosarcoma lines amenable for in vivo studies and cancer stem cell (CSC) characterization. Moreover, it provided clues of the genetic drift of chondrosarcoma cells during the adaptation to grow conditions.

Predictive Capacity and Cutoff Value of Waist-to-Height Ratio in the Incidence of Metabolic Syndrome.

The purpose of this study was to compare the predictive ability of waist-to-height ratio (WHtR) compared with other anthropometric indicators in the incidence of metabolic syndrome (MetS) and to propose cutoff values for its early detection in nursing practice. A longitudinal cohort study was conducted on a sample of 630 workers (137 exposed and 493 nonexposed), free of MetS at baseline. WHtR was compared with body mass index (BMI), waist circumference (WC), and the percentage of body fat (BF%). In the Cox regression, the adjusted values of hazard ratio (HR) were 5.4 (confidence interval [CI] = [3.1, 9.5]) for WHtR and 7.4 (CI = [3.7, 14.9]) for components of MetS. WHtR obtained the largest area under the curve 0.82 (CI = [0.76, 0.88]), and with a cutoff value of 0.54, values were obtained for sensitivity (70%) and specificity (77%). WHtR was the best predictor of incidence of MetS, with a cutoff value of 0.54. Nursing can improve the early detection of MetS by measuring WHtR.

The multikinase inhibitor EC-70124 synergistically increased the antitumor activity of doxorubicin in sarcomas.

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases. Therefore, we studied the antitumor activity of EC-70124, an indolocarbazole analog that have demonstrated a robust ability to inhibit a wide range of pro-survival kinases. Evaluation of the phospho-kinase profile in cell-of-origin sarcoma models and/or sarcoma primary cell lines evidenced that PI3K/AKT/mTOR, JAK/STAT or SRC were among the most highly activated pathways. In striking contrast with the structurally related drug midostaurin, EC-70124 efficiently prevented the phosphorylation of these targets and robustly inhibited proliferation through a mechanism associated to the induction of DNA damage, cell cycle arrest and apoptosis. In addition, EC-70124 was able to partially reduce tumor growth in vivo. Importantly, this compound inhibited the expression and activity of ABC efflux pumps involved in drug resistance. In line with this ability, we found that the combined treatment of EC-70124 with doxorubicin resulted in a synergistic cytotoxic effect in vitro and an increased antitumor activity of this cytotoxic drug in vivo. Altogether, these results uncover the capability of the novel multikinase inhibitor EC-70124 to counteract drug resistance in sarcoma and highlight its therapeutic potential when combined with current treatments.

Validation of a non-invasive method for the early detection of metabolic syndrome: a diagnostic accuracy test in a working population.

OBJECTIVES: A non-invasive method for the early detection of metabolic syndrome (NIM-MetS) using only waist-to-height ratio (WHtR) and blood pressure (BP) has recently been published, with fixed cut-off values for gender and age. The aim of this study was to validate this method in a large sample of Spanish workers. DESIGN: A diagnostic test accuracy to assess the validity of the method was performed. SETTING: Occupational health services. PARTICIPANTS: The studies were conducted in 2012-2016 on a sample of 60 799 workers from the Balearic Islands (Spain). INTERVENTIONS: The NCEP-ATP III criteria were used as the gold standard. NIM-MetS has been devised using classification trees (the χ2 automatic interaction detection method). MAIN OUTCOME MEASURES: Anthropometric and biochemical variables to diagnose MetS. Sensitivity, specificity, validity index and Youden Index were determined to analyse the accuracy of the diagnostic test (NIM-MetS). RESULTS: With regard to the validation of the method, sensitivity was 54.7%, specificity 94.9% and the Validity Index 91.2%. The cut-off value for WHtR was 0.54, ranging from 0.51 (lower age group) to 0.56 (higher age group). Variables more closely associated with MetS were WHtR (area under the curve (AUC)=0.85; 95% CI 0.84 to 0.86) and systolic BP (AUC=0.79; 95% CI 0.78 to 0.80)). The final cut-off values for the non-invasive method were WHtR ≥0.56 and BP ≥128/80 mm Hg, which includes four levels of MetS risk (very low, low, moderate and high). CONCLUSIONS: The analysed method has shown a high validity index (higher than 91%) for the early detection of MetS. It is a non-invasive method that is easy to apply and interpret in any healthcare setting. This method provides a scale of MetS risk which allows more accurate detection and more effective intervention.

FUS-CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK-Dependent Pathway.

Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many types of tumors. In myxoid and round cell liposarcoma (MRCLS), an adipocytic tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have been found as one of the most activated kinases. Here we used a cell-of-origin model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays) and in vivo (chicken chorioallantoic membrane model) approaches. FUS-CHOP expression activated SRC-FAK signaling and increased the invasive ability of MRCLS cells. In addition, FAK expression was found to significantly correlate with tumor aggressiveness in sarcoma patient samples. The involvement of SRC/FAK activation in FUS-CHOP-mediated invasion was further confirmed using the SRC inhibitor dasatinib, the specific FAK inhibitor PF-573228, and FAK siRNA. Notably, dasatinib and PF573228 could also efficiently block the invasion of cancer stem cell subpopulations. Downstream of SRC/FAK signaling, we found that FUS-CHOP expression increases the levels of the RHO/ROCK downstream effector phospho-MLC2 (T18/S19) and that this activation was prevented by dasatinib or PF573228. Moreover, the ROCK inhibitor RKI-1447 was able to completely abolish invasion in FUS-CHOP-expressing cells. These data uncover the involvement of SRC/FAK/RHO/ROCK signaling axis in FUS-CHOP-mediated invasion, thus providing a rationale for testing inhibitors of this pathway as potential novel antimetastatic agents for MRCLS treatment.

[Cardiovascular risk factors in the population at risk of poverty and social exclusión]. / Factores de riesgo cardiovascular en la población en situación de riesgo de pobreza y exclusión social.

GOALS: Detect if there are differences in prevalence, distribution of cardiovascular risk factors and risk according to REGICOR and SCORE's function; between people belonging to different occupational classes and population at risk of social exclusion. DESIGN: Cross-sectional. SITE: Occupational health unit of the City Hall of Córdoba. PARTICIPANTS: Sample availability of 628 people, excluding 59 by age or incomplete data. The group of municipal workers was obtained randomly while all contracted exclusion risk was taken. INTERVENTION: No preventive, diagnostic or therapeutic actions that modify the course of the previous situation of workers were applied. MAIN MEASUREMENTS: Smoke, glucose, lipids, blood pressure and BMI as main variables. T-student were used for comparison of means and percentages for Chi2. Statistical significance attached to an alpha error <5% and confidence interval with a 95% security. Receiver operator curves (ROC) were employed to find out what explanatory variables predict group membership of workers at risk of exclusion. RESULTS: Smoking (95% CI: -.224;-.443), hypercholesterolemia (95% CI: -.127;-.320), obesity (95% CI: -.005;-0.214), diabetes (95% CI: -.060;-.211) and cardiovascular risk were higher in men at risk of exclusion. In women there were differences in the same variables except smoking (P=.053). CONCLUSIONS: The existence of inequalities in prevalence of cardiovascular risk factors is checked. In a context of social crisis, health promotion and primary prevention programs directing to the most vulnerable, they are needed to mit.