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Open Access
November 29, 2023
Abstract
Objectives Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Methods Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. Results The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00–2.07], central laboratory: 11.63 h [6.09–25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5–79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). Conclusions POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet.
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Open Access
November 23, 2023
Abstract
Objectives The results of external quality assurance schemes are evaluated against specifications generally based on biological variation (BV) data. This study was carried out to determine whether new BV values affected the level of compliance to specifications. Our secondary objective was to identify the conditions that would be compromised as a result of poor analytical performance in disease associated markers. Methods This study was based on the results of the SEQC ML External Quality Assurance scheme for the 2015–2022 period. Deviation of the individual result from the target value was estimated. Additionally, we calculated the percentage of results that met the pre-established specification. Results In 97 of the 133 analytes, the level of compliance was maintained in 80–90 % of the results obtained in the two study periods. In 23 analytes, the level of compliance ranged from 51 to 79 % in the two study periods. In ALT, AST and sodium, the level of compliance was ≤50 % of the results obtained in the first study period, with sodium being the only analyte that maintained this poor level of compliance in the second study period. Conclusions The level of compliance to specifications remained independent from the specification used (SEQC ML or EFLM) for the majority of the analytes. The results for sodium ion were below the target value, which may lead to misdiagnosis of hyponatremia. Non-compensated alkaline picrate methods overestimate creatinine, which may produce false information suggestive of kidney failure.
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Open Access
November 23, 2023
Abstract
Objectives In the recent years, liquid chromatography with tandem mass spectrometry has gained popularity in laboratories. This technique has a higher specificity, detects different analytes from a single specimen, measures analytes in distinct matrices, and substantially reduce analytical interference, with respect to immunoassay. The processing and preparation of biological samples are crucial in chromatography. Interferences in blood testing are usually caused by the presence of phospholipids and proteins. The main objective of this study was to improve analytical processes for drug screening by LC-MS/MS using a novel blood sample preparation method based on protein precipitation and removal of phospholipids. Methods An evaluation was performed of a new method for the preparation of blood samples based on protein precipitation and removal of phospholipids by LC-Q-q-LIT. Results Limit of detection, limit of quantification and measurement range were determined for 56 molecules. The results of 11 cases were compared with those obtained using standard blood collection methods and instruments. Conclusions The novel blood preparation and testing method based on LC-Q-q-LIT, a more sensitive technique, has demonstrated to yield comparable results to traditional methods. In addition, this new technique reduces turnaround time and costs.
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Open Access
November 21, 2023
Abstract
Resumen Objetivos La peritonitis bacteriana espontánea es una complicación frecuente y grave de los pacientes cirróticos con ascitis. Actualmente, los antibióticos carbapenémicos son el tratamiento de elección en pacientes con peritonitis nosocomiales o relacionadas con el sistema sanitario. Pese a ello, los estudios de eficacia del ertapenem en pacientes cirróticos con peritonitis bacteriana espontánea son limitados y la farmacocinética y farmacodinamia de este antibiótico continúa siendo desconocida. Así, el objetivo de este estudio es desarrollar y validar procedimientos de medida basados en la cromatografía líquida de alta y rápida eficacia acoplada a la espectrometría de masas en tándem (UHPLC-MS/MS) para medir las concentraciones de ertapenem en el plasma y en el líquido ascítico. Métodos El pretratamiento de las muestras se realiza utilizando una precipitación de proteínas con acetonitrilo. La separación cromatográfica se lleva a cabo en una columna C 18 de fase inversa Acquity ® -UPLC ® -BEH TM (2,1 × 100 mm id, 1,7 µm) utilizando un gradiente no lineal de agua/acetonitrilo que contiene un 0,1 % de ácido fórmico y an un flujo de 0,4 mL/min. El ertapenem y su patrón interno (ertapenem-D 4 ) son detectados mediante espectrometría de masas en tándem en las modalidades de ionización mediante electroespray positiva y de monitorización múltiple de reacción utilizando, como transiciones de masa, 476,2→346,0/432,2 para el ertapenem y 480,2→350,0 para su patrón interno. Resultados No se observan interferencias ni contaminación por arrastre significativas. Las imprecisiones, los sesgos relativos absolutos, así como los efectos matriz y recuperaciones normalizadas son ≤14,5 %, ≤9,3 %, (92,8−104,5) % y (98,8−105,8) %, respectivamente. Los procedimientos de medida cromatográficos son lineales entre (0,50−100) mg/L. Conclusiones Los procedimientos de medida basados en la UHPLC-MS/MS desarrollados y validados podrían ser de utilidad para realizar estudios farmacocinéticos y farmacodinámicos en sujetos con cirrosis hepática que presentan peritonitis bacteriana espontánea tratados con ertapenem.
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Open Access
November 14, 2023
Abstract
Liver fibrosis is the result of chronic liver injury of different etiologies produced by an imbalance between the synthesis and degeneration of the extracellular matrix and dysregulation of physiological mechanisms. Liver has a high regenerative capacity in the early stage of chronic diseases so a prompt liver fibrosis detection is important. Consequently, an easy and economic tool that could identify patients with liver fibrosis at the initial stages is needed. To achieve this, many non-invasive serum direct, such as hyaluronic acid or metalloproteases, and indirect biomarkers have been proposed to evaluate liver fibrosis. Also, there have been developed formulas that combine these biomarkers, some of them also introduce clinical and/or demographic parameters, like FIB-4, non-alcoholic fatty liver disease fibrosis score (NFS), enhance liver fibrosis (ELF) or Hepamet fibrosis score (HFS). In this manuscript we critically reviewed different serum biomarkers and formulas for their utility in the diagnosis and progression of liver fibrosis.
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Open Access
November 14, 2023
Abstract
Objectives Calprotectin (CP) is a calcium and zinc binding protein that is widely measured on faecal samples but its determination in other biological fluids might be of interest. The aim of this work was to validate the measurement of CP in pleural fluid by chemiluminescence. Methods LIAISON ® XL, a fully automated chemiluminescence analyzer, was used for CP quantification on pleural fluid. A validation protocol was designed using both quality control materials provided by the manufacturer and pools of pleural fluid samples. Stability, imprecision, bias, linearity, detection capability and carry over effect were evaluated. Results CP was stable on pleural fluid at least one week, under refrigerated conditions, and four weeks at −80 °C. The observed intra- and inter-day imprecision was between 2.2 and 6.49 %, with a negative bias under 5.51 %. The linearity of the method was verified up to 2,000 ng/mL. The LoQ for the assay was 48.52 ng/mL. A statistically significant carry-over effect was observed after measuring CP concentrations above the upper limit of linearity, but given the observed magnitude, a clinically relevant impact should not be expected. Conclusions Diasorin Liaison ® calprotectin assay allows reliable measurement of CP in pleural fluid.
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Open Access
November 13, 2023
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Open Access
November 13, 2023
Abstract
Calibration of an analytical measurement procedure is an important basis for the reliability of patient results. Many publications and as well as procedures on how to estimate quality control and interpret those results have been become available over the years. In this publication we are focusing on the critical part of the calibration as there are no clear communication or guidelines on how to perform it. Usually only the recommendation of the reagent or instrument manufacturer is available. We would like to point out this gap to invite for a discussion and improvement of the current situation.
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Open Access
October 27, 2023
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Open Access
October 24, 2023
Abstract
Objectives Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor ( VDR ) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D). Methods 165 patients (53 T1D and 112 T2D) were enrolled. BMD was measured by dual-energy X-ray absorptiometry (DEXA). Plasma osteocalcin (OC), beta-CrossLaps (β-CTX) and N‐amino terminal propeptide of type I collagen (P1NP) and VDR gene polymorphisms were evaluated. Results Participants were 53 T1D (41 years [31–48]) and 112 T2D (60 years [51–66]). BMD were not statistically different between the groups. OC (p<0.001) and P1NP levels (p<0.001) were higher in patients with T1D. The areas under the curve for the prediction of bone pathology were 0.732 (p=0.038) for OC in T1D and 0.697 (p=0.007) in T2D. A significant association was found between lower lumbar BMD and the A allele of BsmI (p=0.03), the A allele of ApaI (p=0.04) and the allele C of the Taql (p=0.046). Also, a significant correlation was found with higher OC levels and the G allele of BsmI (p=0.044), C allele of ApaI (p=0.011), T allele of Taql (p=0.006) and with C allele of FokI (p=0.004). Conclusions The high negative predictive value of the cut-off point for OC suggests that could be useful in excluding the risk suffering bone loss, allowing offering a personalized clinical approach to prevent this pathology.
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Open Access
October 23, 2023
Abstract
Resumen Objetivos Los resultados de los programas de garantía externa de la calidad se evalúan frente a especificaciones generalmente basadas en los datos de variación biológica (VB). En este trabajo se pretende comprobar, por un lado, si el cumplimiento de especificaciones varía con la aplicación de nuevos valores de VB y, por otro lado, señalar qué patologías estarían comprometidas debido a una prestación analítica poco satisfactoria de sus mensurandos clave. Métodos El material utilizado son los resultados de los programas externos de la SEQC ML desde 2015 hasta 2022. El método es estimar la desviación del resultado individual respecto al valor diana considerado y calcular el porcentaje de resultados que cumplen la especificación pre-establecida. Resultados En 97 de los 133 mensurandos el cumplimiento se mantiene entre el 80 y el 100 % de los resultados obtenidos en los dos períodos estudiados. En 23 mensurandos el grado de cumplimiento oscila entre el 51 y el 79 % en los dos periodos. En ALT, AST y sodio el grado de cumplimiento es igual o menor al 50 % de los resultados en el primer período, quedando en este grupo únicamente el sodio en el segundo período. Conclusiones Para la mayoría de los mensurandos estudiados el cumplimiento se mantiene independiente de la especificación empleada (SEQC ML o EFLM). Los resultados de ion sodio están por debajo del valor diana, por lo que podrían darse casos de diagnóstico falso de hiponatremia. Los métodos de picrato alcalino no compensado sobreestiman la creatinina, pudiendo ocasionar falsa información de insuficiencia renal.
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Open Access
October 23, 2023
Abstract
Resumen Objectivos La lipoproteína(a) (Lp(a)) es cada vez más relevante en la evaluación de pacientes con riesgo vascular debido a su asociación con una mayor incidencia de eventos cardiovasculares. Este estudio tiene como objetivo identificar las características clínicas de los pacientes con niveles elevados de Lp(a) atendidos en consultas externas por riesgo vascular. Métodos Estudio observacional retrospectivo en donde se compararon las características clínicas de los pacientes con niveles elevados de Lp(a) (≥50 mg/dL) con la de los pacientes con valores normales (<50 mg/dL), en un total de 878 pacientes atendidos por riesgo o enfermedad vascular durante los años 2021 y 2022. Resultados Los valores más elevados de Lp(a) se asociaron de forma independiente con una mayor probabilidad de antecedentes de enfermedad arterial periférica (p=0,024), hipercolesterolemia familiar poligénica (HFP, p=0,030) e hipercolesterolemia familiar combinada (HFC, p=0,015), el tratamiento de inhibidores de PCSK9 (p=0,029) y la combinación de estatinas y ezetimiba (p=0,018). Sin embargo, no se obtuvieron diferencias significativas para las variables antecedentes familiares de enfermedad cardiovascular precoz (p=0,143) ni para antecedentes de enfermedad cardiovascular previa (p=0,063) a diferencia de lo identificado en otras series. Conclusiones Los niveles elevados de Lp(a) se asociaron con antecedentes de enfermedad arterial periférica, diagnóstico de HFP y HFC, así como con la necesidad de utilizar tratamientos hipolipemiantes más intensos.
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Open Access
October 20, 2023
Abstract
Objectives The purpose of this proof-of-concept study was to investigate whether a commercially available urine dipstick may provide potentially useful information for screening plasma glucose and bilirubin in human plasma samples. Methods Glucose and bilirubin were assayed in 60 anonymized lithium-heparin residual plasma samples using the Roche COBAS 8000 or after pipetting 10 µL of plasma onto the pads of a commercial urine dipstick. Semiquantitative urine test results obtained with the dipstick were directly compared to paired test results obtained with COBAS. Results Median plasma glucose values between COBAS and dipstick were slightly different (5.8 vs. 5.6 mmol/L; p=0.040), while no significant difference was found in bilirubin values between COBAS and dipstick (11.2 vs. 8.6 μmol/L; p=0.090). The Spearman’s correlation between COBAS and dipstick was 0.83 (95% CI, 0.73–0.90; p<0.001) for plasma glucose and 0.78 (95% CI, 0.66–0.87; p<0.001) for plasma bilirubin, respectively. Cumulative agreement between COBAS and dipstick was high for both glucose (88%; kappa statistic statistics, 0.75; 95% CI, 0.58–0.92; p<0.001) and bilirubin (88%; kappa statistics, 0.76; 95% CI, 0.60–0.92; p<0.001). Conclusions The results of this proof-of-concept study indicate that the commercial urine test strip used in our study provides acceptable performance for screening plasma glucose and bilirubin levels compared with reference laboratory assays.
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Open Access
October 20, 2023
Abstract
Objectives Recently, vitamin D status has been associated with prostate cancer risk. However, some studies argue that there is no association of vitamin D with prostate cancer risk and serum prostate-specific antigen (PSA) concentrations. No clear conclusions can be drawn from the studies found in the literature. Our aim was to assess the relationship between PSA and 25-hydroxyvitamin D [25(OH)D]. Methods We selected 415 individuals without prostate pathologies and subgroups were generated according to age and 25(OH)D. Statistical analyses were performed using Shapiro–Wilk test, Student’s t and ANOVA tests, and Pearson’s correlation. Besides, the minimum sample size needed to obtain statistically significant results between groups according to 25(OH)D concentration was calculated and a Student’s t-test for paired samples was performed to study individuals with two PSA measurements over time, where 25(OH)D concentration increased or decreased more than 25 %. Results We observed a slight correlation between age and PSA concentration (r=0.379, p<0.001). However, we found no significant differences when we compared PSA concentrations between groups according to 25(OH)D concentrations (p=0.891): 1.25 ± 1.32 μg/L (group with 25(OH)D<50 nmol/L) and 1.17 ± 0.90 (group with 25(OH)D≥50 nmol/L). Pearson’s correlation coefficient was close to 0. The minimum samples size to obtain statistically significant results was 815,346 men, and we observed no differences in PSA concentrations in individuals with two measurements. Conclusions Our findings show no association in men without prostate pathologies, based on 25(OH)D levels.
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Open Access
October 11, 2023
Abstract
Background Statins are one of the most prescribed medications in developed countries as the treatment of choice for reducing cholesterol and preventing cardiovascular diseases. However, a large proportion of patients experience adverse drug reactions, especially myotoxicity. Among the factors that influence the diversity of response, pharmacogenetics emerges as a relevant factor of influence in inter-individual differences in response to statins and can be useful in the prevention of adverse drug effects. Content A systematic review was performed of current knowledge of the influence of pharmacogenetics on the occurrence and prevention of statin-associated adverse reactions and clinical benefits of preemptive pharmacogenetics testing. Summary Genetic variants SLCO1B1 (rs4149056) for all statins; ABCG2 (rs2231142) for rosuvastatin; or CYP2C9 (rs1799853 and rs1057910) for fluvastatin are associated with an increase in muscle-related adverse effects and poor treatment adherence. Besides, various inhibitors of these transporters and biotransformation enzymes increase the systemic exposure of statins, thereby favoring the occurrence of adverse drug reactions. Outlook The clinical preemptive testing of this pharmacogenetic panel would largely prevent the incidence of adverse drug reactions. Standardized methods should be used for the identification of adverse effects and the performance and interpretation of genotyping test results. Standardization would allow to obtain more conclusive results about the association between SLCO1B1, ABCG and CYP2C9 variants and the occurrence of adverse drug reactions. As a result, more personalized recommendations could be established for each statin.
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Open Access
October 9, 2023
Abstract
Resumen Objetivos La cromatografía líquida acoplada a la espectrometría de masas ha ganado en popularidad en los laboratorios en los últimos años debido a una mayor especificidad de la técnica, la posibilidad de determinar múltiples analitos en una sola inyección de la muestra, la medición de analitos en una variedad de matrices diferentes y a una drástica reducción de las interferencias analíticas en comparación con el inmunoensayo. El tratamiento y preparación de las muestras biológicas es un proceso esencial cuando éstas han de ser analizadas mediante sistemas cromatográficos. Los principales interferentes en el análisis de las muestras de sangre son los fosfolípidos y las proteínas. El objetivo principal de este estudio es mejorar la sistemática analítica toxicológica en el cribado general de fármacos mediante la técnica LC-MS/MS a través de un nuevo método de preparación de muestras en sangre basado en la precipitación de proteínas y eliminación de fosfolípidos. Métodos Se ha evaluado el nuevo método de preparación de muestras en sangre basado en la precipitación de proteínas y eliminación de fosfolípidos mediante la tecnología LC-Q-q-LIT. Resultados Se ha determinado el límite de detección, el límite de cuantificación y rango de medición para las 56 moléculas seleccionadas y se han comparado los resultados de once casos con las extracciones e instrumentación tradicionales. Conclusiones La metodología propuesta de preparación de muestras en sangre y análisis mediante técnicas más sensibles como LC-Q-q-LIT ha resultado comparable a la metodología tradicional en cuanto a resultados y, ofreciendo, además, una reducción de tiempo y coste.
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Open Access
October 5, 2023
Abstract
Resumen Introducción Las estatinas son unos de los medicamentos más prescritos en los países desarrollados por ser el tratamiento de elección para reducir los niveles de colesterol ayudando así a prevenir la enfermedad cardiovascular. Sin embargo, un gran número de pacientes sufre reacciones adversas, en especial miotoxicidad. Entre los factores que influyen en la diversidad de respuesta, la farmacogenética puede jugar un papel relevante especialmente en la prevención de los efectos adversos asociados a estos medicamentos. Contenido Revisión de los conocimientos actuales sobre la influencia de la farmacogenética en la aparición y prevención de las reacciones adversas asociadas a estatinas, así como del beneficio clínico del test farmacogenético anticipado. Resumen Variaciones genéticas en SLCO1B1 (rs4149056) para todas las estatinas; en ABCG2 (rs2231142) para rosuvastatina; o en CYP2C9 (rs1799853 y rs1057910) para fluvastatina están asociadas a un incremento de las reacciones adversas de tipo muscular y a una baja adherencia al tratamiento. Además, diversos fármacos inhibidores de estos transportadores y enzimas de biotransformación incrementan la exposición sistémica de las estatinas favoreciendo la aparición de las reacciones adversas. Perspectiva La implementación clínica del análisis anticipado de este panel de farmacogenética evitaría en gran parte la aparición de reacciones adversas. Además, la estandarización en la identificación de los efectos adversos, en la metodología e interpretación del genotipo, permitirá obtener resultados más concluyentes sobre la asociación entre las variantes genéticas del SLCO1B1, ABCG y CYP2C9 y la aparición de reacciones adversas y establecer recomendaciones para alcanzar tratamientos más personalizados para cada estatina.
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Open Access
September 22, 2023
Abstract
Resumen El hueso es mucho más que un reservorio de calcio y fósforo. Su disposición lacuno-canalicular ofrece una importante vía de intercambio con la circulación y actualmente, el esqueleto se considera un gran órgano endocrino, con acciones que van más allá del control del balance fosfocálcico mediado por el factor fibroblástico 23 (FGF23). Paralelamente al efecto modulador de las adipoquinas sobre el remodelado óseo, diversas proteínas óseas, como la osteocalcina y la esclerostina, ejercen cierta acción contra-reguladora sobre el metabolismo energético, posiblemente en un intento de asegurar los enormes requerimientos energéticos del remodelado. En esta interacción del hueso con otros tejidos, especialmente el adiposo, participa la señalización canónica Wnt/β-catenina y por ello la esclerostina, una proteína osteocítica que inhibe esta señalización, emerge como un potencial biomarcador. Es más, su participación en diversas patologías le posiciona como diana terapéutica, existiendo un anticuerpo anti-esclerostina, recientemente aprobado en nuestro país para el tratamiento de la osteoporosis. Esta revisión aborda el carácter endocrino del hueso, el papel de la osteocalcina y, especialmente, el papel regulador y modulador de la esclerostina sobre remodelado óseo y la homeóstasis energética a través de su interacción con la señalización canónica Wnt/β-catenina, así como su potencial utilidad como biomarcador.
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Open Access
August 28, 2023
Abstract
Bone markers are a group of substances released into circulation during bone formation and/or resorption. These substances can be measured in blood and urine to obtain information about metabolic bone disorders. This review provides an insight into factors influencing bone marker variability and describes different approaches to minimize variability and interpret results appropriately. Variability in bone marker concentrations results from biological and analytical variability across assays. Other influencing factors include gender, age, physical exercise, circadian rhythm, and diet. The multiplicity of influencing factors hinders the establishment of accurate reference values. Gaining a deep understanding of bone marker variability is the first step to ascertain their clinical usefulness. Bone marker variability can be minimized by controlling as many variables as it is possible and through the standardization of patient preparation and sample collection and handling.
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Open Access
July 24, 2023
Abstract
Resumen Los biomarcadores óseos son un conjunto de sustancias que son liberadas a la circulación sanguínea durante el proceso de formación y/o resorción ósea y que podemos medir en sangre y orina para obtener información sobre los trastornos metabólicos del hueso. La revisión traza una perspectiva sobre los factores que influyen en la variabilidad de los biomarcadores óseos y describe los aspectos a considerar para reducirla al máximo e interpretar los resultados de manera adecuada. La variabilidad que podemos observar en la concentración de los biomarcadores óseos engloba diversos aspectos que abarcan desde su variabilidad biológica y la variabilidad de los ensayos empleados en su medida hasta la variabilidad derivada de la influencia de numerosos factores, entre los cuales el sexo, la edad, el ejercicio, su ritmo circadiano o la dieta. Todo ello se refleja en la dificultad de establecer valores de referencia precisos. El conocimiento de esta variabilidad es el primer desafío que debe afrontar su empleo en la práctica clínica. Es necesario minimizar la variabilidad de los biomarcadores óseos controlando el máximo de variables que sea posible, así como estandarizando la preparación del paciente antes de la toma de las muestras, así como su obtención y manejo.
