Comparison of Carotid Intima-Media Thickness in Children and Adults With and Without Obesity: A Hysteresis Model.

OBJECTIVE: To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups. METHODS: A quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling. RESULTS: The additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model. CONCLUSION: This practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.

Decrease of Postchemotherapy Complications With the Use of Probiotics in Children With Acute Lymphoblastic Leukemia.

INTRODUCTION: During the administration of antineoplastic drugs, acute complications because of toxicity occur, determining their hospital readmission, visits to the emergency department, use of antimicrobials, and possibilities of presenting systemic infections, impacting on their life quality. METHODS: Through a prospective cohort, 60 children with acute lymphoblastic leukemia were followed-up for 30 days after the hospital discharge because of chemotherapy administration, those patients were previously included in a single-blinded study in which 30 (group 1) received Lactobacillus rhamnosus GG probiotic during the administration of chemotherapy. The remaining 30 patients did not receive probiotics (group 2). There were evaluated gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distension, meteorism, constipation, nausea, and vomit, development of infections, antibiotic use, number of emergency department visits, number of hospitalizations, and sepsis diagnosis. STATISTICAL ANALYSIS: To assess the impact of the use of probiotics, the difference in proportions between both study groups was evaluated. RESULTS: Gastrointestinal manifestations (nausea, vomiting, diarrhea, constipation) occurred in 30% of patients in group 1 versus 63% of group 2 (P=0.009). Nine of 30 patients (30.0%) in group 1 went to the emergency room, versus 33.3% of group 2 (P=0.7). Antimicrobials were used in 8 subjects (26.6%) in group 1 versus 6 subjects (53.3%) in group 2 (P=0.03) suspected of an infectious disease. Four (13.3%) group 1 patients were hospitalized versus 30% of group 2 (P=0.1). Two subjects (6.6%) in group 1 had sepsis versus 7 (23.3%) in group 2 (P=0.07).Conclusions:The results indicate that the use of probiotics can be a great alternative in the improvement of gastrointestinal symptoms and the adverse effects associated with chemotherapy.

Effect of Eicosapentaenoic Acid on Body Composition and Inflammation Markers in Patients with Head and Neck Squamous Cell Cancer from a Public Hospital in Mexico.

INTRODUCTION: Head and neck cancer patients are at high risk of anorexia-cachexia syndrome and literature shows that Eicosapentaenoic acid (EPA) could regulate it. We aim to determine the EPA effect on body composition and pro-inflammatory markers in patients with head neck cancer. MATERIALS AND METHODS: A randomized single-blind placebo-controlled clinical trial was conducted in patients with head and neck squamous cell cancer who received a polymeric diet with 2 g of EPA or a standard polymeric diet for six weeks before antineoplastic treatment. We assessed body composition by bioelectrical impedance analysis and determined IL-1ß, IL-6, TNF-α and IFN-γ, CRP, serum proteins, and blood count at baseline and at the end of the study. RESULTS: 32 patients received EPA (2 g/day) and 32 became controls. A decrease in serum levels of IL-1ß, IL-6, TNF-α, and IFN-γ was observed in the experimental group, as well as regulation of body weight (-0.3 ± 5.9 vs. -2.1 ± 3.7), lean body mass (-0.2 ± 3.8 vs. -1.3 ± 3.6), body fat mass (0.2 ± 3.5 vs. -1.2 ± 3.8), and quality of life (10 ± 33 vs. 5 ± 34). CONCLUSION: Supplementing with 2 g/day of EPA to head and neck cancer patient during antineoplastic treatment regulates serum pro-inflammatory cytokines, body weight, lean body mass, and improve quality of life.

IFITM5-related (type V) osteogenesis imperfecta with evidence of perinatal involvement: A case report.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

The CCR2+ Monocyte Subsets Increase in Obese Boys but Not Girls with Abnormally High Carotid Intima-Media Thickness: A Pilot Study.

The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2+ cell percentage and CCR2 expression in the three monocyte subsets, compared to boys with IMT < p75. The CCR2+ cell percentage and CCR2 expression in the three monocyte subsets significantly correlated with increased IMT and insulin resistance in boys but not girls, where the CCR2+ nonclassical monocyte percentage had the strongest associations (r = 0.73 and r = 0.72, respectively). The role of CCR2+ monocyte subpopulations in identifying an abnormally high IMT shows a marked sexual dimorphism, where boys seem to be at higher subclinical atherosclerosis risk than girls.

Isomers of conjugated linoleic acid induce insulin resistance through a mechanism involving activation of protein kinase Cε in liver cells.

Conjugated linoleic acid (CLA) constitutes a group of isomers derived from linoleic acid. Diverse studies have suggested that these unsaturated fatty acids have beneficial effects on human health. However, it has also been reported that their consumption can generate alterations in hepatic tissue. Thus, in the present study, we evaluated the effect of two of the major isomers of CLA, cis-9, trans-11-CLA and trans-10, cis-12-CLA, in the regulation of insulin signaling in a hepatic cell model, clone 9 (C9). We found that the two isomers decrease insulin-stimulated phosphorylation of the main proteins involved in insulin signaling, such as Akt at Ser473 and Thr308, the insulin receptor at Tyr1158, IRS-1 at Tyr632, and GSK-3 at Ser9/21. Protein expression, however, was unaffected. Interestingly, both isomers of CLA promoted phosphorylation and activation of PKCε. Inhibition of PKCε activity by a dominant-negative form or knockdown of endogenous PKCε prevented the adverse effects of CLA isomers on insulin-induced Akt phosphorylation. Additionally, we also found that both isomers of CLA increase phosphorylation of IRS-1 at Ser612, a mechanism that probably underlies the inhibition of IRS-1 signaling by PKCε. Using confocal microscopy, we found that both isomers of CLA induced lipid accumulation in C9 cells with the presence of spherical cytosolic vesicles, suggesting their identity as neutral lipid droplets. These findings indicate that cis-9, trans-11-CLA and trans-10, cis-12-CLA isomers could have a significant role in the development of insulin resistance in hepatic C9 cells through IRS-1 serine phosphorylation, PKCε activation, and hepatic lipid accumulation.

Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial.

Context: Insulin resistance precedes metabolic syndrome abnormalities and may promote cardiovascular disease and type 2 diabetes in children with obesity. Results of lifestyle modification programs have been discouraging, and the use of adjuvant strategies has been necessary. Objective: This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity. Design: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Setting: Children with obesity were randomly assigned to receive metformin, CLA, or placebo. Results: Intervention had a positive effect in all groups. For insulin sensitivity Rd value (mg/kg/min), there was a statistically significant difference between the CLA vs placebo (6.53 ± 2.54 vs 5.05 ± 1.46, P = 0.035). Insulinemia and homeostatic model assessment of insulin resistance significantly improved in the CLA group (P = 0.045). After analysis of covariance was performed and the influence of body mass index, age, Tanner stage, prescribed diet, and fitness achievement was controlled, a clinically relevant effect size on insulin sensitivity remained evident in the CLA group (37%) and exceeded lifestyle program benefits. Moreover, upregulated expression of the insulin receptor substrate 2 was evident in muscle biopsies of the CLA group. Conclusions: Improvement of insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp and IRS2 upregulation, favored patients treated with CLA.

El índice de masa corporal como predictor de morbimortalidad y consumo de recursos en pacientes internados en la unidad de terapia intensiva / The body mass index as a predictor of morbimortality and resource use in the patients in the intensive care unit / O índice de massa corporal como prognóstico da morbidade e mortalidade e o consumo de recursos em pacientes hospitalizados na unidade de terapia intensiva

Resumen: Introducción: No hay acuerdo en los reportes de la literatura sobre si un índice de masa corporal por arriba de 25 kg/m(2) incrementa, no modifica o disminuye la mortalidad en pacientes en estado crítico. Objetivo: Comparar la mortalidad, morbilidad y consumo de recursos entre individuos con peso normal o bajo (índice de masa corporal IMC < 25 kg/m(2)) versus sujetos con sobrepeso u obesidad (IMC > 25 kg/m(2)). Diseño: Estudio de cohorte prolectiva en una unidad de terapia intensiva. Pacientes: Se incluyeron 159 personas en el estudio. Método: Se colectaron variables demográficas y clínicas, incluyendo peso y talla para calcular el índice de masa corporal. Se registraron datos de escalas de gravedad de la enfermedad SAPS-3, de falla orgánica Bruselas y de intervención terapéutica NEMS (como subrogado de consumo de recursos). El análisis estadístico fue multivariado; fue considerada significativa una p < 0.05. Resultados: Al comparar individuos con IMC < 25 kg/m(2) con aquellos con un IMC mayor no hubo diferencia estadísticamente significativa en mortalidad y consumo de recursos. Sin embargo, al replantear el estudio y comparar sujetos con IMC < a 30 kg/m(2) con aquellos con un IMC mayor, se encontró diferencia significativa en mortalidad entre ambos grupos y un tamaño del efecto considerable en cuanto a consumo de recursos en personas con un IMC > 30 kg/m(2). Conclusiones: En México debemos cambiar el punto de corte del índice de masa corporal a 30 kg/m(2) cuando comparemos mortalidad y consumo de recursos en los enfermos internados en la UTI. Este estudio abre la posibilidad de realizar un estudio multicéntrico para confirmar estos resultados.

Abstract: Introduction: There is disagreement over if a body mass index (BMI) above 25 kg/m(2) increases, decreases or does not alter the mortality in critically ill patients. Objective: To compare the mortality, morbidity and resource use among patients with normal or low body mass index (< 25 kg/m(2)) versus patients with overweight or obesity (> 25 kg/m(2)). Design: Study of a prolective cohort in an intensive care unit. Patients: One hundred fifty-nine patients were included in the study. Methods: Demographic and clinical data (including weight and height for the calculation of the body mass index) were collected, as well as scores of severity of illness SAPS-3, organic failure (Brussels) and therapeutic intervention NEMS (as a surrogate marker of resource use). The statistical analysis was multivariate, with a significance of p < 0.05. Results: When we compared patients with a BMI < 25 kg/m(2) versus those with BMI above 25 kg/m(2), we did not find statistical differences in mortality and resource use. However, when we changed the cutoff point of BMI to 30 kg/m(2), we found statistically significant differences in mortality and an important effect size in the resource use between both groups. Conclusions: In México we should change the cutoff point of the body mass index to 30 kg/m(2) when we compare mortality and resource use in those patients in the ICU. This study suggests the possibility of making a multicenter study to confirm these findings.

Resumo: Introdução: Não há nenhum acordo nos relatos da literatura se um índice de massa corporal acima de 25 kg/m(2) incrementa, não altera ou diminui a mortalidade em pacientes em estado crítico. Objetivo: Comparar a mortalidade, morbidade e consumo de recursos entre os pacientes com peso normal ou baixo (índice de massa corporal IMC < 25 kg/m(2)) versus pacientes com sobrepeso e obesidade (IMC > 25 kg /m(2)). Desenho: Estudo prospectivo de coorte. Pacientes: 159 pacientes foram incluídos no estudo. Método: Foram coletadas variáveis demográficas clínicas, incluindo peso e altura para calcular o índice de massa corporal. Foram coletados dados da escala de gravidade da doença SAPS-3, a falha orgânica Bruselas e a intervenção terapêutica NEMS (como o consumo de recursos sub-rogado). A análise estatística foi multivariada considerando significativa uma p < .05. Resultados: Ao comparar os pacientes com IMC < 25 kg/m(2) com aqueles com um IMC superior não houve diferença estatisticamente significativa na mortalidade e consumo de recursos. No entanto, ao reformular o estudo e comparar pacientes com IMC < 30 kg/m(2) com aqueles com um IMC superior, se encontrou uma diferença significativa na mortalidade entre os dois grupos e um impacto significativo em termos de consumo de recursos em pacientes com IMC > 30 kg/m(2). Conclusões: No México temos que mudar o ponto de corte do índice de massa corporal à 30 kg/m(2) quando comparamos a mortalidade e o consumo de recursos em pacientes internados na UTI. Este estudo abre a possibilidade de um estudo multicêntrico para confirmar estes resultados.