Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case–control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696–0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine (p < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injuryInstitute of Health Carlos III grants (PI17/01989) and Servicio Andaluz de Salud (F2-0071-2015

Effect of Preoperative Infusion of Levosimendan on Biomarkers of Myocardial Injury and Haemodynamics After Paediatric Cardiac Surgery: A Randomised Controlled Trial

Trial registry number: EudraCT 2012-005310-19.Key Points A randomised controlled trial was conducted to test the hypothesis that preoperative infusion of levosimendan would decrease myocardial injury biomarkers (troponin I and B-type natriuretic peptide) after paediatric cardiac surgery more efficiently than placebo. Troponin I and B-type natriuretic peptide levels were higher with placebo at 12 and 24 h after cardiopulmonary bypass, but the differences were not statistically significant. Lactic acid level was significantly lower and oxygen delivery (DO2) was significantly higher at 12 and 24 h after surgery in Levosimendan group. The results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan.Objective The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients’ cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass. Methods In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery. Results Troponin I levels were higher in the placebo group at 0, 12, and 24 h after cardiopulmonary bypass, although the mean differences between the study groups and the 95% confidence intervals (CIs) for troponin I levels did not present statistically significant differences at any of the three time points considered (mean differences [95% CIs] − 3.32 pg/ml [− 19.34 to 12.70], − 2.42 pg/ml [− 19.78 to 13.95], and − 79.94 pg/ml [− 266.99 to 16.39] at 0, 12, and 24 h, respectively). A similar lack of statistically significant difference was observed for B-type natriuretic peptide (mean differences [95% CIs] 36.86 pg/dl [− 134.16 to 225.64], − 350.79 pg/dl [− 1459.67 to 557.45], and − 310.35 pg/dl [− 1505.76 to 509.82]). Lactic acid levels were significantly lower with levosimendan; the mean differences between the study groups and the 95% CIs for lactate levels present statistically significant differences at 0 h (− 1.52 mmol/l [− 3.19 to − 0.25]) and 12 h (− 1.20 mmol/l [− 2.53 to − 0.10]) after cardiopulmonary bypass. Oxygen delivery (DO2) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m2 [122.34–1162.67] and 832.35 ml/min/m2 [58.15 to 1651.38], respectively). Conclusions Levosimendan does not significantly improve patients’ postoperative troponin I and B-type natriuretic peptide profiles during the immediate postoperative stage in comparison with placebo, although both were numerically higher with placebo. Levosimendan, however, significantly reduced lactic acid levels and improved patients’ DO2 profiles. These results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan

Killer immunoglobulin-like receptor and cancer

Introducción: Las células natural killer (NK) juegan un papel importante en la defensa contra las células tumorales. El desarrollo y la función de las células NK se rige por un equilibrio dinámico entre la inhibición y la activación de los receptores de la superficie celular, incluidos los receptores KIR. Pacientes y método: se realiza un estudio de casos y controles que compara a un grupo de 46 ni˜nos diagnosticados de enfermedades malignas, el grupo control está constituido por 82 ni˜nos sanos. Se determinaron y compararon entre grupos los genes, haplotipos y ligandos KIRs. Resultados: no existen diferencias en genes KIRs, haplotipos KIRs ni en ligandos de genes KIRs entre grupos. Sin embargo, al estudiar conjuntamente KIRs y ligandos, k2DS1 C2 fue significativamente superior en el grupo de ni˜nos oncológicos (p◦=◦0,016). Conclusiones: Nuestros resultados no proporcionan evidencia de una asociación entre enfermedades oncológicas pediátricas con genotipos y grupos de genes KIRs. El genotipo k2DS1 C2 podría predisponer a la susceptibilidad a procesos malignos en la población infantil.Introduction: Natural killer (NK) cells play an important role in defense against tumor cells. The development and function of NK cells is governed by a dynamic balance between inhibition and activation of cell surface receptors, including KIR receptors. Patients and method: A case-control study is carried out that compares a group of 46 childrendiagnosed with malignant diseases, the control group is made up of 82 healthy children. KIRsgenes, haplotypes and ligands were determined and compared between groups.Results: There are no differences in KIRs genes, KIRs haplotypes or in KIRs gene ligands betweengroups. However, when KIRS and ligands were jointly studied, k2DS1 C2 was significantly higherin the group of cancer children (p◦=◦0.016).Conclusions: Our results do not provide evidence of an association between pediatric cancerdisease with genotypes and groups of genes KIRs. The k2DS1 C2 genotype could predispose tosusceptibility to malignant processes in children.Instituto de Salud Carlos III - FEDER (números decontrato:PI12 / 00378, SAS-PI-0239/2012, AC-0073-2013

Ceruloplasmin and its clinical relevance as an indactor of cardiovascular risk factor in a school population of Granada

La ceruloplasmina también conocida como ferroxidasa, pertenece a la familia de las proteínas sensibles a la inflamación, siendo su función principal la de transportar el cobre en la sangre. Si bien, además de esta función transportadora, en la actualidad, son numerosos los estudios que han intentado hacer uso de la determinación de sus concentraciones séricas, como un indicador predictivo del riesgo de padecer trastornos cardiovasculares en pacientes que presentan sobrepeso u obesidad. Los resultados obtenidos en este estudio confirman la existencia de una correlación significativa entre los niveles séricos de ceruloplasmina y el estado nutricional de los sujetos, lo que significa que para la población de escolares valorada, las concentraciones séricas de esta proteína suponen un importante factor para predecir el riesgo de padecer trastornos cardiovasculares.Also known as ferroxidase ceruloplasmin, belongs to the family of inflammation-sensitive proteins, and its main function to transport copper in the blood. Although, in addition to this transport function, at present, there are numerous studies that have attempted to use the determination of serum concentrations as a predictive indicator of cardiovascular risk in patients who are overweight or obese. The results of this study confirm the existence of a significant correlation between serum ceruloplasmin and nutritional status of the subjects, which means that for the population of students assessed, serum levels of this protein are an important predictor the risk of cardiovascular disease

Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children.

La transmisión vertical del virus de la hepatitis C (HCV-VT) es una ruta principal de infección por HCV en niños, pero los factores de riesgo no se comprenden completamente. Este estudio analizó el papel de la interleucina 28B (IL28B) en HCV-VT y en la eliminación espontánea de HCV entre los infantes infectados. Entre 1991 y 2009, se reclutaron 145 madres para este estudio: 100 eran HCV-RNA+ve / VIH negativo (HIV-ve), con 128 niños, y 33 eran HCV-RNA-ve / HCV anticuerpo+ve, con 43 niños. Los infantes fueron evaluados para HCV-RNA al nacer y a intervalos regulares hasta la edad de 6 años. Se determinó IL28B (polimorfismo de nucleótido simple rs12979860) en las madres y los niños. Se asumió HCV-VT cuando los niños presentaron HCV-RNA+ve en dos muestras de sangre consecutivas. Los infantes infectados por HCV-VT se categorizaron como: (1) viremia transitoria con posterior HCV-RNA-ve y sin seroconversión; (2) infección persistente con seroconversión. De las 31 madres con polimorfismo CC, 19 (61%) eran HCV-RNA+ve, mientras que entre las 68 madres con polimorfismo no-CC, 56 (82%) eran HCV-RNA+ve. En total, 26 de 128 (20%) infantes nacidos de madres HCV-RNA+ve adquirieron la infección por HCV, pero solo 9 (7%) estaban crónicamente infectados. La tasa de HCV-VT fue mayor entre las madres con mayor viremia de HCV. No se detectó HCV-VT en las mujeres HCV-RNA-ve. Ni el estado de IL-28 de las madres ni el de los niños se asoció con un mayor riesgo de HCV-VT. Los factores que influyen en la eliminación viral entre los niños infectados fueron el genotipo no-1 y el genotipo CC de IL28B. En la regresión logística, el polimorfismo CC del niño fue el único predictor de la eliminación de HCV en el genotipo-1 de HCV. Conclusión: La alta carga viral materna es el único factor predictivo de HCV-VT. IL28B no juega ningún papel en HCV-VT, pero el polimorfismo CC de IL28B en niños se asocia independientemente con la eliminación espontánea del genotipo-1 de HCV entre los niños infectados. (HEPATOLOGÍA 2011;53:1830-1838

Influence of family environment of the development of obesity and overweight in a population of school children in Granada (Spain)

La literatura científica existente plantea la necesidad de entender la conducta alimentaria como un proceso cíclico e interactivo, según el cual los hábitos y la conducta alimentaria de los padres llevan a sus hijos a desarrollar estrategias especificas de alimentación, esto es, a la definición de conductas alimentarias propias, lo que tendrá su reflejo en los indicadores nutricionales del niño. Los objetivos de este estudio han sido verificar la existencia de una asociación significativa entre el nivel educativo de los padres y el estado nutricional de sus hijos, comprobar si existe una relación directa entre el estado nutricional de los hijos y quién es la persona que elabora el menú familiar y determinar el posible vínculo entre el estado nutricional de los hijos y el tiempo que éstos dedican a la práctica del ocio sedentario. La población de estudio estuvo constituida por 718 niños y adolescentes escolares de entre 9 y 17 años de edad, pertenecientes todos ellos a trece centros educativos públicos y privados de la ciudad de Granada y de su provincia. Se trata de un estudio descriptivo, transversal y multicéntrico en el que se llevó a cabo una valoración del estado nutricional de toda la población de alumnos correspondientes a trece centros educativos. Mediante el uso de técnicas de antropometría se valoraron las variables peso, talla y, con ello, el índice de masa corporal.According to recent research, eating behaviour should be understand as a cyclical and interactive process in which parental eating habits cause children to develop specific eating strategies as well as their own eating habits. Needless to say, this interactive process is reflected and has a direct impact on the nutritional indicators of the children in a family. The objectives of this study were the following: (i) to verify the existence of a significant association between the educational level of parents and the nutritional state of children in the same family; (ii) to discover if there is a direct relation between the nutritional state of children and the person that decides the menu and/or prepares family meals; (iii) to determine if there is a link between the nutritional state of children and the time that they spend on sedentary leisure activities. The sample population was composed of 718 school children and adolescents, 9-17 years of age, who A descriptive, transversal, and multicentric study was performed that evaluated the nutritional state of the entire sample by using anthropometric techniques to assess weight, height, and body mass index

Obesidad de una población de escolares de Granada: evaluación de la eficacia de una intervención educativa

Objetivos: El objeto del presente trabajo es estudiar la prevalencia de la obesidad y el sobrepeso en una población de escolares y verificar la efectividad de la intervención educativa desarrollada sobre esos alumnos en términos de mejora de los valores percentilados del índice de masa corporal. Material: La población valorada está compuesta por 977 escolares de entre 9 y 17 años de edad, pertenecientes a 13 centros educativos públicos de la ciudad de Granada y de su provincia (España). Metodología: Se trata de un estudio longitudinal, analítico, multicéntrico y observacional de cohortes, desarrollado en tres fases. En primer lugar, valoración del estado nutricional, mediante técnicas antropométricas (peso, talla e índice de masa corporal, seis pliegues cutáneos y cuatro perímetros corporales) así como la presión arterial. Una segunda fase en la que se desarrolló la intervención educativa sobre la alimentación y el ejercicio físico. En la fase final se evaluó la efectividad de la intervención. Resultados: Se encontró una mayor prevalencia de obesidad en las chicas de entre 12 y 13 años (15,1%). En los chicos, la prevalencia de obesidad fue inferior hasta los 13 años, aunque después mostraron un creciente incremento de dicha prevalencia (12,6%). Se produjo una reducción significativa de los valores de IMC en los dos sexos, aunque más significativa entre las chicas. Conclusiones: Existe un incremento alarmante en la prevalencia de sobrepeso y obesidad entre la población valorada. La reducción significativa de las puntuaciones en el IMC confirma la efectividad de la intervención educativa desarrollada.Objectives: The objective of this research was to study the prevalence of obesity and excess weight in a population of school children and adolescents, and to verify the effectiveness of an educational intervention, as reflected in the variation of their body mass index values. Materials: The population sample was composed of 977 school children and adolescents from 9 to 17 years of age, belonging to 13 public elementary schools and high schools in the city and province of Granada (Spain). Methodology: This longitudinal cohort study was analytical, muticentric, and observational. It was carried out in three phases. The first phase involved the evaluation of the nutritional state of the sample population by means of anthropometric measurements (weight, height, body mass index, six skin folds and four body perimeters) as well as arterial blood pressure. The second phase entailed an educational intervention focusing on good nutritional habits and physical exercise. The third and final phase evaluated the effectiveness of the intervention. Results: A higher obesity prevalence (15.1%) was found in school girls between 12 and 13. In the case of boys, obesity prevalence was lower up to age 13 though afterwards, it progressively increased (12.6%). The educational intervention produced an important reduction in body mass index values in both sexes though this reduction was more significant in young females. Conclusions: There is a currently an alarming increase in obesity and overweight prevalence among the population evaluated in this study. The significant reduction in body mass index values resulting from this research confirmed the effectiveness of the educational intervention to reduce excess weight

Bone mineralization status measured by dual energy radiographic densitometry in preterm infants fed commercial formulas

We have studied the effect of two preterm commercial infant formulas with different calcium and phosphorus contents on the mineral balance and bone mineralization of 30 preterm infants at 1 month of age. Bone mineralization was measured by dual energy X-ray densitometry. The formula supplying a higher content of calcium and phosphorus promoted higher mineral retention (P , 0.01) as well as higher bone mineral content (1.556 vs. 1.073 g, P , 0.01) and 2 bone mineral density (0.458 vs. 0.424 g / cm , P , 0.05), approaching values of the control group, which comprised a cohort of 15 preterm newborns whose gestational age was 4 weeks older than the subjects selected to be fed with the formulas. The intake of calcium correlated with retention (r 5 0.69); the phosphorus intake also correlated with phosphorus retention (r 5 0.95). Intakes of calcium and phosphorus correlated with the bone mineral content (r 5 0.65) and with bone mineral density (r 5 0.49). We conclude that formulas for preterm infants should not have a calcium content lower than 120 mg / 100 kcal and should have a calcium / phosphorus ratio of about 2 to promote adequate bone mineralization