Adipokines, insulin resistance, and adiposity as a predictors of metabolic syndrome in child survivors of lymphoma and acute lymphoblastic leukemia of a developing country.

BACKGROUND: There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. METHODS: Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. RESULTS: The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. CONCLUSIONS: Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship between MS with risk of developing type 2 diabetes and cardiovascular disease, it is imperative to implement prevention measures in this population and especially in developing countries where these pathologies have become the leading cause of death.

The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial.

BACKGROUND: N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE: To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS: This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES: Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS: LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION: At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).

Effect of long-chain omega-3 polyunsaturated fatty acids on cardiometabolic factors in children with acute lymphoblastic leukemia undergoing treatment: a secondary analysis of a randomized controlled trial.

Introduction: Increased triglycerides (TGs) are a major risk factor for cardiovascular disease. Furthermore, hypertriglyceridemia is commonly associated with a reduction of high-density lipoprotein cholesterol (HDL-C) and an increase in atherogenic small-dense low-density lipoprotein (LDL-C) levels. Studies provide support that polyunsaturated omega-3 fatty acids (ω3-LCPUFAs) are cardioprotective and have antithrombotic and anti-inflammatory effects. The potential effects of ω3-LCPUFAs on cardiometabolic factors and anti-inflammatory actions in children with acute lymphoblastic leukemia (ALL) are limited. This is a secondary analysis of a previous clinical trial registered at clinical trials.gov (# NCT01051154) that was conducted to analyze the effect of ω3-LCPUFAs in pediatric patients with ALL who were receiving treatment.Objective: To examine the effect of supplementation with ω3-LCPUFAs on cardiometabolic factors in children with ALL undergoing treatment. Methods: Thirty-four children (placebo group: 20 patients; ω3-LCPUFAs group: 14 patients) aged 6.7 ± 2.7 years who were newly diagnosed with ALL were evaluated. Children were randomized to receive either ω3-LCPUFAs or placebo capsules (sunflower oil). ω3-LCPUFAs were administered in the form of 500-mg soft capsules. The ω3-LCPUFA capsules contained 225 mg of DHA, 45 mg of EPA, and 20 mg of another ω3-LCPUFAs. The omega-3 dose was administered at a rate of 0.100 g/kg of body weight/day for three months. Main outcomes: Fasting cholesterol, HDL-C, very-low-density lipoprotein (VLDL-C), TGs, atherogenic index of plasma (AIP), android/gynoid ratio (A/GR), IL-6, TNF-α, and percentage of fat mass (DXA) were measured in all patients. Fatty acid analyses in red blood cells were performed with gas chromatography. Results: We found significantly lower levels of TGs (p=0.043), VLDL-C (p=0.039), IL-6 (p=0.025), and AIP (p=0.042) in the ω3-LCPUFAs group than in the placebo group at three months. In contrast, the total cholesterol concentration was higher at 3 months in the ω3-LCPUFAs group than in the placebo group (155 mg/dl vs. 129 mg/dl, p=0.009). The number of children with hypertriglyceridemia (85% vs. 50%; p=0.054) tended to be lower between the time of diagnosis and after 3 months of supplementation with ω3-LCPUFAs. Conclusion: These findings support the use of ω3-LCPUFAs to reduce some adverse cardiometabolic and inflammatory risk factors in children with ALL. Clinical trial registration: ClinicalTrials.gov, identifier NCT01051154.

Duchenne muscular dystrophy: RANK/RANKL/OPG (receptor activator of nuclear factor-kB/RANK ligand/osteoprotegerin) system and glucocorticoids.

Duchenne muscular dystrophy (DMD) is an X-linked inherited disorder. Patients present with decreased bone mineral density (BMD) due to glucocorticoid therapy and progressive muscle weakness. Bone remodeling allows bone volume and structure to be maintained and controlled by local and systemic factors. These include the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, a determining pathway in the balance between bone formation and resorption. Disruptions in this complex, caused by factors such as glucocorticoids, can affect bone metabolism. The extensive action of the RANK/RANKL/OPG pathway suggests an influence on dystrophic muscle pathophysiology. This review aimed to highlight some aspects of the RANK/RANKL/OPG system, the effect of glucocorticoids on this pathway, and the pathophysiology of the patient with DMD.

La distrofia muscular de Duchenne (DMD) es un trastorno hereditario ligado al cromosoma X. Los pacientes presentan una disminución de la densidad mineral ósea (DMO) debido a los efectos adversos del tratamiento con glucocorticoides y a la debilidad muscular progresiva. El remodelado óseo permite mantener el volumen y la estructura ósea, proceso controlado por factores locales y sistémicos. Entre ellos destaca el sistema del receptor activador del factor nuclear-kB (RANK), su ligando natural RANKL (RANKL) y la osteoprotegerina (OPG), una vía determinante en el equilibrio entre la resorción y formación ósea. Las alteraciones en este complejo, originadas por factores como los glucocorticoides, pueden afectar el metabolismo óseo. La amplia acción de RANKL y OPG ha sugerido una influencia en la fisiopatología de la DMD. El objetivo de esta revisión fue destacar algunos aspectos del sistema RANK/RANKL/OPG, el efecto de los glucocorticoides en esta vía y la fisiopatología del paciente con DMD.

[Usefulness of a nutritional strategy on dyslipidemia in pediatric patients with terminal chronic kidney disease]. / Utilidad de una estrategia nutricional sobre la dislipidemia en pacientes pediátricos con enfermedad renal crónica terminal.

Introduction: Background and objective: in chronic kidney disease (CKD) there are several factors that increase the presence of dyslipidemia. The aim of this study was to identify the usefulness of a nutritional intervention, in children with terminal CKD, on dyslipidemia 6 months after intervention start. Materials and methods: a quasi-experiment study (before and after) was performed. End-stage CKD patients on peritoneal dialysis and hemodialysis were included. Each child underwent a determination somatometry, and lipid profile at the beginning and at 6 months of follow-up. A nutritional guide was made with food traffic lights, turning the food that should be consumed in the least amount possible in red. In addition to including life-size food using educational models. To compare the quantitative variables before and after the intervention, the variables were transformed to their logarithm and a paired Student's t-test was applied. Results: a total of 41 patients were analyzed. After the intervention, the parameters in the lipid profile were modified; meanwhile HDL concentrations increased (41.0 mg/dL vs 44.4 mg/dL, p = 0.048), triglyceride concentrations decreased (227.1 mg/dL vs 185.9 mg/dL, p = 0.007), and these changes persist even after excluding patients who were under lipid-lowering treatment (195 mg/dL vs 171.6, p = 0.049). Regarding the state of dyslipidemia, hypertriglyceridemia decreased, without reaching significance (80.5 % vs 62.5 %, p = 0.073). Conclusions: the nutritional intervention improved HDL and triglyceride concentrations 6 months afterwards in children with terminal CKD.

Introducción: Antecedentes y objetivo: en la enfermedad renal crónica (ERC) existen múltiples factores que incrementan la presencia de la dislipidemia. El objetivo fue identificar la utilidad de una intervención nutricional sobre la dislipidemia, en niños con ERC terminal, a los 6 meses del inicio de la intervención. Materiales y métodos: estudio cuasiexperimental (antes y después). Se incluyeron pacientes con ERC terminal en diálisis peritoneal y hemodiálisis. A cada niño se le realizaron una somatometría y un perfil de lípidos al inicio y a los 6 meses de seguimiento. Se realizó un manual de alimentación con semaforización de los alimentos, poniendo de color rojo los alimentos que se deben consumir en la menor cantidad posible, además de incluir alimentos a tamaño real utilizando modelos educativos. Para comparar las variables cuantitativas antes y después de la intervención se transformaron las variables a su logaritmo y se aplicó la "t" de Student pareada. Resultados: se analizaron 41 pacientes. Posteriormente a la intervención se modificaron los parámetros del perfil lipídico; las concentraciones de HDL se incrementaron (41,0 mg/dL vs. 44,4 mg/dL, p = 0,048), mientras que las concentraciones de triglicéridos disminuyeron (227,1 mg/dL vs. 185.9 mg/dL, p = 0,007), lo cual persiste incluso una vez excluidos aquellos pacientes que se encontraban bajo tratamiento hipolipemiante (195 mg/dL vs. 171,6, p = 0,049). En cuanto al estado de dislipidemia, la hipertrigliceridemia disminuyó sin alcanzar la significancia (80,5 % vs. 62,5 %, p = 0,073). Conclusiones: la intervención nutricional mejoró las concentraciones de HDL y triglicéridos pasados 6 meses de la intervención en niños con ERC terminal.

The leptin/adiponectin ratio as prognostic marker for dyslipidemia during 1 year of follow-up in pediatric patients receiving kidney replacement therapy.

Introduction: Background: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.

Introducción: Antecedentes: la leptina y la adiponectina se asocian con enfermedad cardiovascular en los pacientes con enfermedad renal crónica (ERC) y podrían ser factores pronósticos útiles. Objetivos: explorar la utilidad del cociente leptina/adiponectina (LAR) para predecir la presencia o empeoramiento de la dislipidemia durante 1 año de seguimiento en niños que reciben terapia de reemplazo renal (TRR). Material y métodos: se realizó un estudio de cohortes prospectivo. Se incluyeron pacientes pediátricos con TRR de entre 8 y 17 años que estaban en hemodiálisis o diálisis peritoneal. Al inicio del estudio se determinaron el perfil lipídico, los niveles de adiponectina y leptina, y las mediciones somatométricas, incluido el porcentaje de grasa corporal. En el seguimiento de un año, se reevaluó el perfil de lípidos. Resultados: de los 70 pacientes incluidos, la mediana de edad fue de 13 años y no hubo predominio de sexo (52,8 % de varones). Al final del seguimiento, los pacientes se dividieron en tres grupos: aquellos sin dislipidemia (SD), aquellos que desarrollaron o experimentaron un empeoramiento de su dislipidemia (ED) y aquellos con dislipidemia persistente (PD). Un LAR > 0,85 (OR: 16,7) y el porcentaje de grasa corporal (OR: 1,46) se asociaron con un mayor riesgo de ED y PD a los 12 meses, independientemente del nivel de urea, la puntuación Z del IMC, el tratamiento con benzafibrato, el tiempo de progresión de la ERC y el tratamiento de reemplazo. Conclusiones: un LAR > 0,85 y el porcentaje de grasa corporal al inicio del seguimiento se asociaron fuertemente con la presencia, persistencia o empeoramiento de la dislipidemia a los 12 meses de seguimiento en niños con TRR.

Cardiometabolic Factors in Pediatric Patients with Chronic Diseases.

BACKGROUND: The prevalence of chronic diseases (CDs) in the pediatric population has increased due to technological advances that decrease mortality and increase survival. AIM OF THE STUDY: To compare the frequency of cardiometabolic factors (CFs) among pediatric patients with CDs with those among children with obesity and overweight without CDs. METHODS: This study was a cross-sectional study. Pediatric patients from 6-17 years of age were included. A total of 333 patients with CD were studied, and of these patients, 77 had difficult-to-control epilepsy, 183 had chronic kidney disease (CKD), and 73 underwent kidney transplants; in addition, a comparison group was included, consisting of 286 overweight and obese children without any other pathologies. We performed anthropometry, blood pressure, glucose, insulin, and lipid profiling on all of the patients. Statistical analysis was conducted as follows: Chi2 tests were used to compare the CFs between the groups. RESULTS: We included 619 patients from 6-17 years old. Patients with CDs had a low frequency of obesity (12.4%) but a high frequency of the remaining CFs. Hypertriglyceridemia (65%), hypoalphalipoproteinemia (49%) and systemic arterial hypertension (46.5%) were the most common CFs, particularly among subjects with CKD and kidney transplantation. When comparing the frequencies of these CFs with those in the obesity/overweight group, hypertriglyceridemia (p <0.05) was more common in patients with CDs. CONCLUSIONS: In patients with CDs, dyslipidemia, hypertension, and hyperglycemia occur at frequencies that are the same as or higher than those in overweight/obese children, but when the CD patients are overweight/obese, it increases their frequency.

[From research to practice: clinical phases for drug development]. / De la investigación a la práctica: fases clínicas para el desarrollo de fármacos.

Clinical trials become very relevant in the development of new drugs when their pharmacokinetics, pharmacodynamics, efficiency, safety and possible adverse effects are being assessed. So new drugs are available for their daily use in patients, a model has been proposed for more than four decades; This model consists in the realization of sequential research studies, which were called clinical phases I, II, III and IV, which begin once the drugs' effects have been verified in cellular and animal models (preclinical phase). In this article, the general characteristics of each of the clinical phases are synthesized but, apart from that, the modifications that have been done over the years are described with the purpose of making new drugs available in a quicker way.

Los ensayos clínicos toman gran relevancia en el desarrollo de nuevos fármacos al evaluar la farmacocinética, farmacodinamia, eficacia, seguridad y sus posibles efectos adversos. Para que un nuevo fármaco esté disponible para su uso cotidiano en pacientes, desde hace más de cuatro décadas se propuso un modelo que consiste en la realización de estudios de investigación secuenciales que se denominaron fases clínicas I, II, III y IV, las cuales se inician una vez que se han comprobado los efectos del fármaco en modelos celulares y animales (fase preclínica). En este artículo se sintetizan las características generales de cada una de las fases clínicas, pero además se describen las modificaciones que se han realizado en el trascurso de los años, a fin de disponer rápidamente de nuevos fármacos.

Nutritional status and cytokine concentration during chemotherapy in Mexican children: A longitudinal analysis.

OBJECTIVE: The aim of this study was to assess whether the nutritional status of children with cancer is influenced by variations in cytokine concentrations observed during chemotherapy. We also evaluated whether this relationship could be modified by nutritional status at diagnosis and type of cancer. METHODS: Mexican children with lymphoma or solid tumors were evaluated at diagnosis and at 2- and 6-mo follow-up visits. Blood samples were obtained to determine serum prealbumin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, leptin concentrations, and hemoglobin. Children were classified as undernourished (UN) or well nourished (WN), according to prealbumin concentration. The influence of each cytokine on prealbumin concentration was analyzed by time-series regression model. RESULTS: Fifty patients (ages 2-17 y) were enrolled. There were 17 children with lymphomas and 33 with solid tumors. At baseline, 56% were UN and 26% presented anemia; the frequencies of UN children were higher for those with lymphoma than for those with a solid tumor (P = 0.003). By nutritional status, UN children presented lower leptin (P = 0.002) but higher IL-6 concentrations (P = 0.009) than the WN group. Children with lymphoma presented lower prealbumin (P = 0.003), but higher TNF-α (P = 0.001) and IL-6 (P = 0.011) concentrations than those with solid tumors. At follow-up, the concentration of prealbumin increased and IL-6 decreased in children with lymphoma. Multivariate analysis demonstrated that decreases in prealbumin concentration at the end of follow-up were associated with increases in IL-6 and TNF-α concentration during chemotherapy. CONCLUSIONS: These results suggest that the cytokine responses during chemotherapy are related to nutritional status at the end of 6 mo of treatment regardless of the initial nutritional status and the type of cancer.

Evidence of muscle loss delay and improvement of hyperinsulinemia and insulin resistance in Duchenne muscular dystrophy supplemented with omega-3 fatty acids: A randomized study.

BACKGROUND & AIMS: Duchenne Muscular Dystrophy (DMD) is the most prevalent dystrophy of childhood and is characterized by generalized motor delays due to progressive muscular weakness, leading to loss of muscle mass. Additionally, patients with DMD develop obesity, hyperinsulinemia, and Insulin Resistance (IR). Omega-3 Long-Chain PolyUnsaturated Fatty Acids (Ω-3LCPUFA) increase fat mass, decrease lean mass, and decrease hyperinsulinemia and IR. The aim of this study was to analyze the impact of Ω-3LCPUFA consumption on lean mass, fat mass, hyperinsulinemia, and IR in children with DMD. METHODS: This placebo-controlled, double-blind, randomized study was carried out in 28 patients with DMD supplemented with 2.9 g/d of Ω-3LCPUFA (n = 14) or sunflower oil (placebo, n = 14) during 6 months. Serum glucose and insulin were measured at baseline and thereafter at months 3 and 6 of the intervention to estimate IR by HOmeostasis Model Assessment. Body composition was assessed by Dual Energy X-ray Absorptiometry. RESULTS: The percentage of change in EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes was significantly (p < 0.05) higher in boys who consumed Ω-3LCPUFA than in the placebo group. Lean mass and fat mass (both in g/kg of Body Weight [BW]) had a trend toward being higher (p = 0.07 at month 3 and p = 0.085 at month 6) and lower (p = 0.05 at month 3 and p = 0.085 at month 6) respectively, in boys with DMD supplemented with Ω-3LCPUFA compared with the placebo group. The loss of lean mass was delayed in the Ω-3LCPUFA group; it started at month 6 but, in placebo, it started at month 3 of supplementation in comparison with the baseline of each group. Fasting insulin, percentage of boys with hyperinsulinemia, and IR were similar between the placebo and Ω-3LCPUFA groups during the 6 months of supplementation. The percentage of boys with IR was significantly (p = 0.045) lower at month 6 of supplementation in the Ω-3LCPUFA group than in the placebo group. CONCLUSION: This study suggests that Ω-3LCPUFA (2.9 g/day) intake during 6 months likely slows the progression of muscle loss, decreases the fat mass, and reduces IR in boys with DMD. The findings of this study provide scientific background for conducting a randomized trial focused of confirming the possible beneficial role of Ω-3LCPUFA on the previously mentioned alterations mentioned in boys with early muscle damage (without fibrosis) DMD. This research was registered at clinicaltrials.gov (NCT018264229).

[Android/gynecoid ratio as a prognostic factor for dyslipidemia in pediatric patients with chronic kidney disease]. / Cociente androide/ginecoide como factor pronóstico para dislipidemia en pacientes pediátricos con enfermedad renal crónica.

INTRODUCTION: Background: there are multiple factors that increase the presence of dyslipidemia in chronic kidney disease (CKD). Objective: to determine if the android/gynecoid ratio (A/GR) has utility as a cardiometabolic factor for dyslipidemia in pediatric patients with chronic renal failure. Materials and methods: cohort study. Patients with terminal CKD in peritoneal dialysis and hemodialysis were included. Determinations of body composition, body mass index (BMI), and lipid profile were assessed for each patient. Subsequently, somatometry and lipid profile were performed at 6 and 12 months of follow-up. Statistical analysis: to identify the difference between the initial somatic and biochemical variables, and at 6 and 12 months, the Friedman test was applied. The Spearman coefficient determined the correlation of bodily and biochemical variables. Results: twenty-one patients were analyzed. Tryglycerides (TGL) serum at 12 months of follow-up increased significantly (6 vs 12 months, p = 0.05), without evidence of an increase in the Z score of the BMI (p = 0.98) or total cholesterol (p = 0.49). Body fat, fat percentage and Z score BMI did not correlate with changes in cholesterol and triglyceride levels at 6 and 12 months; however, the A/GI presented a statistically significant association with the change in serum concentrations of TGL at 6 (r = 0.65, p = 0.003) and 12 months of follow-up (r = 0.54, p = 0.02). Conclusions: the A/GI showed an association with the increase in the serum concentration of TGL at 12 months of follow-up.

INTRODUCCIÓN: Introducción: los pacientes con enfermedad renal crónica (ERC) deben ser considerados como un grupo de alto riesgo cardiovascular, ya que existen múltiples factores que incrementan la presencia de dislipidemia. Objetivo: determinar si el cociente androide/ginecoide (CA/G) tiene utilidad como factor cardiometabólico para dislipidemia en pacientes pediátricos con insuficiencia renal crónica Materiales y métodos: estudio de una cohorte. Se incluyeron pacientes con ERC terminal en diálisis peritoneal y hemodiálisis. A cada paciente se le realizó determinación de la composición corporal, índice de masa corporal (IMC) y perfil de lípidos. Posteriormente, se realizó somatometría y perfil de lípidos a los 6 y 12 meses de seguimiento. Análisis estadístico: para identificar la diferencia entre las variables somatométricas y bioquímicas iniciales, a los 6 y 12 meses se aplicó la prueba de Friedman. El coeficiente de Spearman determinó la correlación de variables corporales y bioquímicas. Resultados: se analizaron 21 pacientes. Las concentraciones séricas de los triglicéridos a 12 meses de seguimiento aumentaron significativamente (6 vs. 12 meses; p = 0,05), sin evidencia de un incremento en el score Z del IMC (p = 0,98) o colesterol total (p = 0,49). La grasa corporal, su porcentaje y score Z del IMC no se correlacionaron con los cambios en los niveles del colesterol y triglicéridos a los 6 y 12 meses; sin embargo, el CA/G presentó una asociación estadísticamente significativa con la modificación en las concentraciones séricas de los triglicéridos a los 6 (r = 0,65, p = 0,003) y 12 meses de seguimiento (r = 0,54, p = 0,02). Conclusiones: el CA/G mostró asociación al incremento en la concentración sérica de triglicéridos a 12 meses de seguimiento.

Two parenteral amino acid solutions and plasma levels of amino acids in the neonate: A randomized trial.

OBJECTIVE: In neonates on total parenteral nutrition (TPN), amino acids may be a risk factor for developing total parenteral nutrition-associated cholestasis (TPNAC). We aimed, first, to compare methionine, cysteine, and taurine plasma levels between neonates on TPN who were receiving an intravenous amino acid solution based on a breast milk aminogram and those on an intravenous solution of pediatric amino acids based on an umbilical cord aminogram, and second, to determine the frequency of TPNAC. METHODS: A double-blind randomized controlled trial was conducted. Ninety-four neonates with a birthweight of 1000g or more and a gestational age of 30 wk or older were admitted and enrolled. Blood samples were obtained at 0, 7, and 14 d of TPN, and plasma amino acid concentrations were determined by ultra-high-resolution liquid chromatography. Continuous variables were compared using the Wilcoxon rank-sum test or Student's t test; categorical variables were compared using the Fisher exact test. RESULTS: Thirty-five neonates completed the study (Primene, n = 14; TrophAmine, n = 21). On day 14, methionine plasma concentrations were significantly lower in the Primene group than in the TrophAmine group (27 µmol/L versus 32.9 µmol/L, P = 0.044); the taurine concentration was significantly higher in the same group (72.4 µmol/L versus 45.3 µmol/L, P < 0.0001). There were no differences in TPNAC incidence. CONCLUSIONS: Administering an intravenous solution of pediatric amino acids based on the umbilical cord aminogram yielded a higher taurine and lower methionine plasma concentration than did administering a similar solution based on the breast milk aminogram.

[The influence of different factors on energy intake and Basal metabolic rate in children with cancer]. / Factores que influyen en la tasa metabólica basal e ingesta de energía del paciente pediátrico con cáncer.

OBJECTIVE: to identify the Influence of different factors on energy intake and basal metabolic rate in children with cancer at diagnosis. METHODS: the basal metabolic rate and energy intake were measured during hospitalization and before treatment. The basal metabolic rate and energy from foods were measured by indirect calorimetry. Data were compared by Student t test and a multiple linear regression. RESULTS: energy intake ranged from 636 to 3063 kcal/d, mean 1956 +/- 530 kcal/d. Measured basal metabolic rate was within 10 % of predict for Schofield equation in ten of fourteen patients. Four patients were classified as hypometabolic. Energy intake was related to kind of tumor (solid tumor), sex (males) and loss weight, while basal metabolic rate was related to the age and sex, but only the age reached statistical significance (p < 0.01). CONCLUSIONS: the most influent variables on basal metabolic rate and energy intake were the variables related with age, sex and nutritional status at diagnosis. Physician should be consider the energy requirements of children in order to establish an appropriate nutritional and oncology therapy, and consequently, modify the risk of nutritional deterioration in order to improve the prognostic of patients.

Potential therapeutic impact of omega-3 long chain-polyunsaturated fatty acids on inflammation markers in Duchenne muscular dystrophy: A double-blind, controlled randomized trial.

BACKGROUND & AIMS: Duchenne Muscular Dystrophy (DMD) is the most frequent dystrophy in childhood generated by a deficiency in dystrophin. DMD is a neuromuscular disease and its clinical course comprises chronic inflammation and gradual muscle weakness. Supplementation of omega-3 long chain-Polyunsaturated Fatty Acids (ω-3 long chain-PUFA) reduces inflammatory markers in various disorders. The goal of this research was to analyze the influence of ω-3 long chain-PUFA intake on gene expression and blood inflammatory markers in boys with DMD. METHODS: In a placebo-controlled, double. Blind, randomized trial, boys with DMD (n = 36) consumed 2.9 g/day of ω-3 long chain-PUFA or sunflower oil as control, in capsules, for a period of 6 months. Blood was analyzed at baseline and at months 1, 2, 3, and 6 of supplementation for expression of inflammatory markers in leukocytes and serum. RESULTS: There was high adherence to capsule intake (control: 95.3% ± 7.2%, and ω-3 long chain-PUFA: 97.4% ± 3.7% at month 6). Enrichment of EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes increased significantly in patients supplemented with ω-3 long chain-PUFA compared with the placebo group during the 6 months of supplementation. Messenger RNA (mRNA) of the Nuclear Factor kappa beta (NF-κB) and its target genes InterLeukin 1 beta (IL-1ß) and IL-6 was downregulated significantly (p < 0.05) in leukocytes from DMD boys supplemented with ω-3 long chain-PUFA for 6 months, compared to the placebo group. Omega-3 long chain-PUFA intake decreased the serum IL-1ß (-59.5%; p = 0.011) and IL-6 (-54.8%; p = 0.041), and increased the serum IL-10 (99.9%, p < 0.005), in relation to those with placebo treatment. CONCLUSION: Supplementation with ω-3 long chain-PUFA 2.9 g/day is well-tolerated, has a beneficial reductive effect on proinflammatory markers, and increases an anti-inflammatory marker, indicating that ω-3 long chain-PUFA could have a potential therapeutic impact on chronic inflammation in DMD. This research is registered at clinicaltrials.gov (NCT018264229).

Body composition by dilution of deuterium oxide in Mexican children with lymphoma and solid tumors.

OBJECTIVE: Scant information exists about the changes in body composition of children during the first months of chemotherapy. These changes can be determined by using a better method than the body mass index. This study compared the changes of body composition by dilution of deuterium oxide in Mexican children with lymphoma and with solid tumors. METHODS: Seventeen patients were enrolled and classified as having lymphoma or solid tumor. Body composition was measured by a deuterium dilution technique after the first course of chemotherapy and again after 2 and 6 mo of therapy. Data were compared by means of paired t and Student's t tests. Simple linear regression was applied to examine the relation between age and changes in fat mass (FM) and fat-free mass (FFM). RESULTS: The groups were similar at baseline. Six months after initiation of chemotherapy, weight and height had increased (P < 0.05) in the lymphoma group, whereas only height had increased in the solid-tumor group; total body water, FM, and FFM increased in the lymphoma group (P < 0.01) but not in the solid-tumor group. Age did not influence FM or FFM in either group. CONCLUSION: In children with lymphoma whose treatment included corticosteroid use, increase in FM content was demonstrated during the first 6 mo of treatment. In patients with solid tumors, FM content did not change during treatment. With an increase in FM content, one should bear in mind that overweight and obesity may result in cardiovascular disease and development of breast cancer in adult life.

Duchenne muscular dystrophy: RANK/RANKL/OPG (receptor activator of nuclear factor-kB/RANK ligand/osteoprotegerin) system and glucocorticoids / Distrofia muscular de Duchenne: el sistema RANK/RANKL/OPG (receptor activador del factor nuclear-kB/ligando de RANK/osteoprotegerina) y glucocorticoides

Abstract Duchenne muscular dystrophy (DMD) is an X-linked inherited disorder. Patients present with decreased bone mineral density (BMD) due to glucocorticoid therapy and progressive muscle weakness. Bone remodeling allows bone volume and structure to be maintained and controlled by local and systemic factors. These include the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, a determining pathway in the balance between bone formation and resorption. Disruptions in this complex, caused by factors such as glucocorticoids, can affect bone metabolism. The extensive action of the RANK/RANKL/OPG pathway suggests an influence on dystrophic muscle pathophysiology. This review aimed to highlight some aspects of the RANK/RANKL/OPG system, the effect of glucocorticoids on this pathway, and the pathophysiology of the patient with DMD.

Resumen La distrofia muscular de Duchenne (DMD) es un trastorno hereditario ligado al cromosoma X. Los pacientes presentan una disminución de la densidad mineral ósea (DMO) debido a los efectos adversos del tratamiento con glucocorticoides y a la debilidad muscular progresiva. El remodelado óseo permite mantener el volumen y la estructura ósea, proceso controlado por factores locales y sistémicos. Entre ellos destaca el sistema del receptor activador del factor nuclear-kB (RANK), su ligando natural RANKL (RANKL) y la osteoprotegerina (OPG), una vía determinante en el equilibrio entre la resorción y formación ósea. Las alteraciones en este complejo, originadas por factores como los glucocorticoides, pueden afectar el metabolismo óseo. La amplia acción de RANKL y OPG ha sugerido una influencia en la fisiopatología de la DMD. El objetivo de esta revisión fue destacar algunos aspectos del sistema RANK/RANKL/OPG, el efecto de los glucocorticoides en esta vía y la fisiopatología del paciente con DMD.

Adiposity and Insulin Resistance in Children from a Rural Community in Mexico.

BACKGROUND AND AIMS: The study of the incidence of overweight and obesity as well as body composition and insulin resistance in children from rural communities is scarce. The aims of the study were a) to characterize the adiposity and homeostasis model assessment of insulin resistance (HOMA-IR) in school-age children from a rural community and b) to determine factors associated with fat mass and HOMA-IR in this population. METHODS: A total of 41 school-aged children (15 males and 26 females; 9.9 ± 2.5 years old) from a Mexican rural community was studied. Trained observers had previously assessed the children's nutritional status during the first 6 months of life. Anthropometry, energy intake, physical activity, body composition and biochemical parameters were measured. RESULTS: The overall prevalence of overweight/obesity was 7.3%. The mean energy intake of children was below international recommendations (1,235 ± 400 kcal/day). A higher percentage of fat mass was observed in females (20.3 ± 8.5) than in males (14.1 ± 5.1) (p = 0.006). There were seven children with IR, but we did not observe a correlation between HOMA and BMI percentiles (Pearson's r = 0.09, p = 0.57). In a regression model, gender (females) was the primary factor associated with the percentage of fat mass. The growth velocity during the first 6 months of life was associated with HOMA-IR. CONCLUSIONS: There is a low frequency of overweight and obesity in children from rural communities in Mexico. However, these children appear to have increased risk of adiposity and insulin resistance.

Correlación entre el gasto y el aporte de energía en neonatos hospitalizados en una unidad de cuidados intensivos / Correlation between energy consumption and intake in infants hospitalized in an intensive care unit

Introducción. Una alimentación adecuada es esencial en el manejo del niño en estado crítico. Este estudio analiza la correlación entre el aporte total de energía (ATE) y el gasto energético total (GET) de pacientes hospitalizados en una Unidad de Cuidados Intensivos Neonatales (UCIN), considerando si nació pretérmino (PT), recibió alimentación parenteral (AP), o tratamiento quirúrgico (TQ). Métodos. Estudio transversal con 29 pacientes evaluados después de alcanzar estabilidad hemodinámica y ventilatoria. El GET se estimó mediante calorimetría indirecta, y el ATE sumando la energía administrada por vía enteral y parenteral. El análisis estadístico incluyó correlación de Spearman, U Mann-Whitney, prueba exacta de Fisher y regresión múltiple. Resultados. Catorce pacientes nacieron PT, y 21 recibieron TQ. Al momento del estudio, 14 recibían AP y 63% estaban desnutridos. El ATE fue mayor para los PT (P =0.022), los de AP (P =0.038) y los de TQ (P =0.046); el GET fue mayor en los PT (P =0.003). La correlación entre GET y ATE fue significativa sólo para alimentación enteral (r =0.518, P =0.046). El ATE fue inadecuado en 85.1% de los pacientes. Conclusiones. El ATE para niños atendidos en la UCIN parece ser inadecuado cuando se calcula por ecuaciones; se sugiere utilizar la determinación del gasto energético por calorimetría indirecta por lo menos en pacientes bajo el régimen de AP total.

Introduction. An adequate feeding is essential in the management of critically ill infants. This study analyzes the association between total energy intake (TEI) and total energy consumption (TEC) of patients hospitalized in a neonatal intensive care unit (NICU) taking into account whether were born preterm (PT), received parenteral nutrition (PN), or underwent surgical treatment (ST). Methods. A cross-sectional design including 29 patients hospitalized in a NICU after hemodynamic and ventilatory stability was conducted. TEC was determined by indirect calorimetry and TEI by the summation of the energy administered by enteral and parenteral pathways. The statistical analysis included, Spearman correlation, U Mann-Whitney test, exact Fisher test, and multiple regression. Results. Fourteen patients were born PT, 21 underwent ST; 14 were under PN regime at the moment of the study and 63% were undernourished. TEI was higher in PT (P =0.022), PN (P =0.038), and ST (P =0.046) patients; TEC was greater only in PT infants (P =0.003). TEC correlated with TEI only in patients receiving enteral nutrition (r=0.518, P =046). TEI was inadequate in 85.1% of the patients. Conclusion. The amount of energy administered to patients hospitalized in the NICU is inadequate when it is estimated by standardized equations. We suggest determining TEC by indirect calorimetry at least in patients under total PN.