Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Influence of Cerebral Vasodilation on Blood Reelin Levels in Growth Restricted Fetuses.

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases.

Estrategia para el diagnóstico de las dislipidemias. Recomendación 2018 / Strategy for the diagnosis of dyslipidaemias

Las dislipidemias son alteraciones del metabolismo lipídico que cursan con concentraciones de lípidos alteradas, tanto por exceso como por defecto. Estas alteraciones están fuertemente asociadas con el proceso aterosclerótico, y se ha demostrado que el control de dichas alteraciones consigue disminuir la incidencia de episodios de origen isquémico. Diagnosticar las dislipidemias desde un punto de vista etiológico es muy importante, ya que el riesgo cardiovascular al que predispone cada una de ellas es diferente, dependiendo del tipo de lipoproteína que esté alterada y de su concentración. Por ello es de gran utilidad disponer de algoritmos diagnósticos sencillos que incluyan magnitudes del metabolismo lipídico disponibles en la mayoría de los laboratorios clínicos, con el fin de realizar el diagnóstico inicial del tipo de dislipidemia, en caso de poseer las herramientas diagnósticas adecuadas identificarla y, en caso contrario, disponer de la información apropiada para recomendar la ampliación del estudio en otro centro que disponga de los recursos necesarios para establecer el diagnóstico

Dyslipidaemias are alterations in lipid metabolism that involve an excess, as well as a deficit, in lipid concentrations. These alterations are strongly associated with atherosclerosis, and it has been shown that its control reduces the incidence of episodes of ischaemic origin. Diagnosing dyslipidaemias from an aetiological point of view is very important, since the cardiovascular risk to which each one predisposes is different, and depends on the type of lipoprotein that is altered and its concentration. For this reason, it is very useful to have simple diagnostic algorithms that include the measurements of lipid metabolism that are available in most clinical laboratories in order to make the initial diagnosis of the type of dyslipidaemia. In the case of having the right diagnostic tools, identify it; and if not, to have the appropriate information to recommend the extension of the study in another centre with resources to establish the diagnosis

Recomendaciones para la estandarización de la medida de lípidos y lipoproteínas. Recomendación (2018) / Recommendations for the standardisation of lipids and lipoproteins measurements. Recommendation (2018)

Este documento describe recomendaciones para la estandarización de la medida de las magnitudes lipídicas, puesto que resultan críticas para la toma de decisiones clínicas. Deben emplearse métodos recomendados validados frente a un método de referencia o definitivo, y materiales de control que cumplan con la Directiva Europea sobre Diagnóstico in vitro; deben cumplir también los objetivos recomendados por el National Cholesterol Education Program (NCEP) y la Sociedad Española de Medicina del Laboratorio (SEQCML). La determinación de colesterol de HDL por métodos homogéneos en equipos automatizados se considera aceptable para la práctica rutinaria, y la fórmula de Friedewald utilizable para estimar la concentración de colesterol de LDL siempre que las concentraciones de triglicéridos sean iguales o inferiores a 200mg/dL (2,3mmol/L); en otro caso, se recomienda utilizar la concentración de colesterol-no-HDL. La cuantificación rutinaria de apolipoproteínas A1 y B, y lipoproteína (a), puede efectuarse por métodos de inmunonefelometría e inmunoturbidimetría, con calibradores trazables a materiales de referencia

Some recommendations are presented for standardising the measurement of lipids and lipoproteins, as they are critical for clinical decisions making. Recommended methods validated against a reference or definitive method should be employed, as well as the use of control materials that comply with European Directives on in vitro diagnostics. Additionally, the chosen methods must comply with the objectives set forth by the National Cholesterol Education Program (NCEP) and by the Spanish Society of Laboratory Medicine (SEQCML). Determination of HDL cholesterol using automatic homogenous methods is considered acceptable for normal clinical practice, and the Friedewald Formula is considered to be usable to estimate LDL cholesterol concentration when triglyceride concentrations are below 200mg/dL (2.3mmol/L). If this should not be the case, the use of non-HDL cholesterol is recommended. Routine quantification of apolipoproteins A1 and B, and lipoprotein (a) can be measured using immunonephelometric or immunoturbidimetric methods, with calibrators that are traceable to reference materials

Removing Lipemia in Serum/Plasma Samples: A Multicenter Study.

BACKGROUND: Lipemia, a significant source of analytical errors in clinical laboratory settings, should be removed prior to measuring biochemical parameters. We investigated whether lipemia in serum/plasma samples can be removed using a method that is easier and more practicable than ultracentrifugation, the current reference method. METHODS: Seven hospital laboratories in Spain participated in this study. We first compared the effectiveness of ultracentrifugation (108,200×g) and high-speed centrifugation (10,000×g for 15 minutes) in removing lipemia. Second, we compared high-speed centrifugation with two liquid-liquid extraction methods-LipoClear (StatSpin, Norwood, USA), and 1,1,2-trichlorotrifluoroethane (Merck, Darmstadt, Germany). We assessed 14 biochemical parameters: serum/plasma concentrations of sodium ion, potassium ion, chloride ion, glucose, total protein, albumin, creatinine, urea, alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate-aminotransferase, calcium, and bilirubin. We analyzed whether the differences between lipemia removal methods exceeded the limit for clinically significant interference (LCSI). RESULTS: When ultracentrifugation and high-speed centrifugation were compared, no parameter had a difference that exceeded the LCSI. When high-speed centrifugation was compared with the two liquid-liquid extraction methods, we found differences exceeding the LCSI in protein, calcium, and aspartate aminotransferase in the comparison with 1,1,2-trichlorotrifluoroethane, and in protein, albumin, and calcium in the comparison with LipoClear. Differences in other parameters did not exceed the LCSI. CONCLUSIONS: High-speed centrifugation (10,000×g for 15 minutes) can be used instead of ultracentrifugation to remove lipemia in serum/plasma samples. LipoClear and 1,1,2-trichlorotrifluoroethane are unsuitable as they interfere with the measurement of certain parameters.

Hemoglobin Le Lamentin in the province of Albacete, Spain: Discovery of 32 cases.

OBJECTIVES: Hemoglobin Le Lamentin (α20(B1)His→Gln) is a ubiquitous variant that has been previously described in a small number of isolated patients. We report the incidental observation of Hb Le Lamentin in a large population from the province of Albacete, in southeastern Spain. Our study investigates possible reasons for the elevated number of carriers of this variant and its implications for the management of diabetes in our region. DESIGN & METHODS: The subjects are 32 diabetic patients whose hemoglobin displayed an unusual peak while they were being tested for glycated hemoglobin at the laboratory of the University General Hospital of Albacete over a 3-year period. Measurements were made by high performance liquid chromatography using a Variant™ II Turbo Kit-2.0, and subsequently the samples of the 32 patients with anomalous peaks were sent to the Hospital Clínico San Carlos (Madrid, Spain) for molecular characterization of any Hb variants. RESULTS: Molecular studies revealed 31 out of 32 patients heterozygous for Le Lamentin, and in one of them, Hb City of Hope was associated with Hb Le Lamentin. The remaining patient was homozygous for the Le Lamentin mutation. Additionally, most patients were native to the northeastern half of the province of Albacete and were unrelated. CONCLUSIONS: Our study describes the largest finding to date of hemoglobin Le Lamentin in a sample of patients. The fact that our region has been perpetually depopulated, with a population that has remained stable in small localities over the centuries, may have favored the survival of the mutation. Since the presence of this variant underestimates the true value of glycated hemoglobin measured by HPLC, it is necessary to systematically review chromatograms.

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

OBJECTIVES: Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). STUDY DESIGN: We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. RESULTS: Adiponectin concentration was negatively correlated with maternal smoking status (ß=-5.208; p<0.001) and positively correlated with levels of insulin (ß=0.621; p=0.002) and PAPP-A (ß=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. CONCLUSION: These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications.

Evaluación multicéntrica de distintos métodos para la determinación de colesterol HDL directo con respecto al colesterol HDL de precipitación / Multicentre evaluation of different methods for the determination of direct HDL-cholesterol compared to the precipitation method

Introducción. Los resultados de los programas de garantía de calidad indican que existen diferencias significativas entre los métodos homogéneos disponibles para la medición del colesterol HDL. Sin embargo, la posible influencia de efectos matriz en las muestras liofilizadas empleadas y la ausencia de un valor verdadero en estas muestras, hace difícil la valoración completa de estos métodos. En este estudio experimental multicéntrico hemos comparado los métodos homogéneos más utilizados en nuestro medio, con respecto al de precipitación de ácido fosfotúngstico-MgCl2. Material y métodos. Cada laboratorio procesó unas 100 muestras de suero de pacientes por uno o dos métodos homogéneos y envió alícuotas congeladas de las muestras analizadas al laboratorio central donde se procesaron por el método de precipitación. Resultados. Las imprecisiones de los métodos homogéneos fueron buenas e inferiores a las de precipitación, que cumplía las especificaciones de calidad para sesgo y error total (ET). Sin embargo, no todos los métodos homogéneos cumplían los objetivos de calidad mínimos, pues algunos procedimientos producían sesgos positivos muy altos (en relación al método de comparación) y uno un sesgo negativo muy bajo. El estudio de la concordancia, realizado estratificando a los pacientes según las concentraciones de colesterol HDL, mostró diferencias entre los métodos. Conclusiones. Estos resultados sugieren que existen discrepancias en la valoración de las magnitudes obtenidas con los métodos homogéneos, probablemente generada por una elevada inexactitud en algunos de ellos y que es conveniente que los laboratorios conozcan las caracteristicas de imprecisión y sesgo del metodo directo que utilizan con respecto al de referencia (AU)

Introduction. The results of quality assurance programs suggest that there are significant differences between the homogeneous methods available for the measurement of HDL cholesterol. However, the possible influence of matrix effects in the lyophilized samples used and the absence of a true value in these samples means that a full assessment of these methods cannot be made. In this multicentre pilot study we compared the most used homogeneous methods in our country with the phosphotungstic acid-MgCl2 method. Material and methods. Each laboratory processed about one hundred serum samples from patients with one or two homogeneous methods and sent frozen aliquots of the samples in special packaging with dry ice to the central laboratory where they were processed by the precipitation method. Results. The imprecision of homogeneous methods were good and lower than those of the precipitation method, and met the quality specifications for bias and total error (TE). However, not all homogeneous methods met the minimum quality objectives, as some procedures produced a very high positive bias (relative to the comparison method) and one, a low negative bias. In addition, the study of the agreement between methods, made by stratifying patients according to HDL cholesterol concentrations, showed differences. Conclusions. These results suggest that there are discrepancies in the assessment of the levels obtained with homogeneous methods, probably due to a high inaccuracy in some of them, and it is advised that the laboratories be aware of the characteristics of inaccuracy and bias of the direct method used compared to the reference method (AU)

[Measurement of NT-proBNP in elderly patients with acute dyspnea: diagnostic and pronostic value]. / Determinación del fragmento N-terminal del propéptido natriurético cerebral (NTproBNP) en pacientes de edad avanzada con disnea aguda: valor diagnóstico y pronóstico.

BACKGROUND AND OBJECTIVE: The aim of our study was to establish weather N-terminal fragment of brain-type natriuretic peptide (NT-proBNP) is useful in the differential diagnosis of dyspnea in elderly patients, and whether its determination has a prognostic value in heart failure (HF). PATIENTS AND METHOD: 79 patients admitted with acute dyspnea at the emergency department were included in our study. The mean age (standard deviation) was 77.56 (8.71) years. 67% had a diagnosis of HF based on clinical and echocardiagraphic criteria. A follow-up of 18 months was performed after discharge. RESULTS: Higher levels of NT-proBNP were found in patients with HF (6,833.54 pg/ml) than in patients with other causes of dyspnea (1,801.99 pg/ml) (p < 0.0001). A cut-off point of NT-proBNP > 730 pg/ml was related to higher rates of readmission due to HF over the next 18 months. CONCLUSIONS: NT-proBNP is a useful biomarker in the differential diagnosis of dyspnea in the elderly population. Its determination has a prognostic roll, stratifying the risk of readmission in HF patients.

Determinación del fragmento N-terminal del propéptido natriurético cerebral (NTproBNP) en pacientes de edad avanzada con disnea aguda: valor diagnóstico y pronóstico / Measurement of NT-proBNP in elderly patients with acute dyspnea: diagnostic and pronostic value

Fundamento y objetivo: El objetivo del presente trabajo ha sido conocer si la determinación del fragmento N-terminal del propéptido natriurético tipo B (NTproBNP) es útil para el diagnóstico diferencial de la disnea en pacientes ancianos, y si tiene algún papel pronóstico en el reingreso por insuficiencia cardíaca (IC) de los pacientes incluidos. Pacientes y método: En el estudio se incluyó a 79 pacientes con disnea aguda, con una edad media (desviación estándar) de 77,56 (8,71) años. Se estableció el diagnóstico de IC en el 67% de ellos a partir de criterios clínicos y ecocardiográficos. Se realizó un seguimiento prospectivo de los pacientes a los 18 meses. Resultados: Los valores de NTproBNP se encontraron más elevados en los pacien tes con IC (6.833,54 pg/ml) que en aquéllos con disnea atribuible a otra causa (1.801,99 pg/ml) (p < 0,0001). En los que presentaron valores de NTproBNP superiores a 730 pg/ml la frecuencia de reingreso a los 18 meses de seguimiento fue mayor. Conclusiones: El NTproBNP es un parámetro útil para diferenciar y clasificar desde el punto de vista pronóstico a pacientes ancianos con disnea asociada a IC

Background and objective: The aim of our study was to establish weather N-terminal fragment of brain-type natriuretic peptide (NT-proBNP) is useful in the differential diagnosis of dyspnea in elderly patients, and whether its determination has a prognostic value in heart failure (HF). Patients and method: 79 patients admitted with acute dyspnea at the emergency department were included in our study. The mean age (standard deviation) was 77.56 (8.71) years. 67% had a diagnosis of HF based on clinical and echocardiagraphic criteria. A follow-up of 18 months was performed after discharge. Results: Higher levels of NT-proBNP were found in patients with HF (6,833.54 pg/ml) than in patients with other causes of dyspnea (1,801.99 pg/ml) (p 730 pg/ml was related to higher rates of readmission due to HF over the next 18 months. Conclusions: NT-proBNP is a useful biomarker in the differential diagnosis of dyspnea in the elderly population. Its determination has a prognostic roll, stratifying the risk of readmission in HF patients

Determinación de cistatina C en pacientes de edad avanzada con insuficiencia cardíaca / Measurement of cystatin C in elderly patients with heart failure

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