Non-infectious uveitis referred for pediatric rheumatologic assessment and management: a Portuguese retrospective study.

BACKGROUND: Pediatric uveitis poses challenges in diagnosis and treatment due to asymptomatic or oligosymptomatic presentations and high rates of intraocular complications. OBJECTIVES: This study aimed to characterize clinical manifestations and treatment approaches of pediatric uveitis patients in a northern Portuguese tertiary hospital. METHODOLOGY: A retrospective study was conducted involving forty-one patients diagnosed with uveitis between 2006 and 2021. All individuals identified by the Opthalmology department were referred to Pediatric Rheumatology outpatient clinic. Demographic, clinical, treatment, and intraocular complications data were collected. RESULTS: Of the patients, 78% had anterior uveitis, 17% had panuveitis, and 5% had intermediate uveitis. Uveitis associated with juvenile idiopathic arthritis was the most common cause (43.9%), predominantly in the oligoarticular, anti-nuclear antibody-positive subgroup. Complications were identified in 80.5% of the patients. Uveitis associated with JIA was diagnosed earlier (5,0 years (3,0-10,5) vs. 9,0 years (5,5-14,0), p=0,036), more frequently in asymptomatic patients (71% vs. 23%, p=0,010), had a more insidious installation (71% vs. 17%, p=0,004), and required more TNF inhibitor treatment (70% vs. 39%, p=0,027). CONCLUSION: The high rates of intraocular complications and systemic pathology association highlight the need for a combined approach of ophthalmology and pediatric rheumatology in the diagnosis and treatment of pediatric uveitis.

Ambulatory chest physiotherapy in mild-to-moderate acute bronchiolitis in children under two years of age - A randomized control trial.

OBJECTIVE: The aim of this study was to compare the role of a chest physiotherapy (CP) intervention to no intervention on the respiratory status of children under two years of age, with mild-to-moderate bronchiolitis. METHODS: Out of 80 eligible children observed in the Emergency Room, 45 children completed the study with 28 randomized to the intervention group and 17 to the control group. The intervention protocol, applied in an ambulatory setting, consisted of combined techniques of passive prolonged slow expiration, rhinopharyngeal clearance and provoked cough. The control group was assessed with no chest physiotherapy intervention. The efficacy of chest physiotherapy was assessed using the Kristjansson Respiratory Score at the admission and discharge of the visit to the Emergency Room and during clinical visits at day 7 and day 15. RESULTS: There was a significant improvement in the Kristjansson Respiratory Score in the intervention group compared to the control group at day 15 [1.2 (1.5) versus 0.3 (0.5); p -value = 0 . 005 , in the control and intervention groups, respectively], with a mean difference (95% CI) of - 0 . 9 ( - 1 . 6 to - 0 . 3 ). CONCLUSION: Chest physiotherapy had a positive impact on the respiratory status of children with mild-to-moderate bronchiolitis. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04260919.

Socioeconomic disadvantage and health in early childhood: a population-based birth cohort study from Portugal.

BACKGROUND: Measuring early socioeconomic inequalities in health provides evidence to understand the patterns of disease. Thus, our aim was to determine which children's health outcomes are patterned by socioeconomics and to what extent the magnitude/direction of the differences vary by socioeconomic measure and outcome. METHODS: Data on early childhood (4 years) health was obtained from Generation XXI birth cohort (n = 8647). A total of 27 health outcomes and 13 socioeconomic indicators at the individual level and neighbourhood level were used to calculate the relative index of inequality (RII). RESULTS: Socioeconomic inequalities were evident across 21 of the 27 health outcomes. Education, occupation and income more often captured inequalities, compared with neighbourhood deprivation or employment status. Using highest maternal education as reference category, we observed that seizures (RII = 8.64), obesity (2.94), abdominal obesity (2.66), urinary tract infection (2.26), language/speech problems (2.24), hypertension (2.08) and insulin resistance (1.33) were heavily socially patterned, much more common in disadvantaged children. Contrastingly, eczema (0.26) and rhinitis (0.26) were more common among more advantaged children. CONCLUSIONS: Socioeconomic inequalities were evident for almost every health outcome assessed, although with varying magnitude/direction according to the socioeconomic indicator and outcome. Our results reinforce that the social gradient in health manifests early in childhood.

Prenatal alcohol exposure affects renal function in overweight schoolchildren: birth cohort analysis.

BACKGROUND: Prenatal ethanol exposure has been shown to reduce nephron endowment in animal models, but the effect of alcohol during human pregnancy on postnatal kidney function has not been explored. We aim to investigate the potential association of maternal alcohol consumption during pregnancy with the offspring renal function, considering potential confounding by intrauterine growth and children's current nutritional status. METHODS: Prospective longitudinal study in a random sample of 1093 children from a population-based birth cohort. Anthropometrics and estimated glomerular filtration rate (eGFR) were assessed at 7 years of age. Multiple linear regression models were fitted, adjusting for child's gender, age, birthweight, and maternal age, education, prepregnancy nutritional status, and smoking. RESULTS: Thirteen percent of mothers consumed alcohol during pregnancy. At 7 years of age, eGFR was significantly lower in children with prenatal alcohol exposure (134 ± 17 vs.138 ± 16 mL/min/1.73m2, p = 0.014). The effect was dose dependent and only present in overweight and obese children, among whom adjusted eGFR was -6.6(-12.0 to -1.1)mL/min/1.73m2 and -11.1(-21.3 to -1.2)mL/min/1.73m2 in those exposed to ≤ 40 g and to > 40 g of alcohol per week, respectively, compared to no consumption (ptrend = 0.002). CONCLUSIONS: Prenatal alcohol exposure has a dose-dependent adverse effect on renal function at school age in overweight and obese children.

Comparison of Kristjansson Respiratory Score and Wang Respiratory Score in infants with bronchiolitis in a hospital emergency department.

OBJECTIVE: Several respiratory scores have been created to evaluate bronchiolitis' severity level, but it is still not clear which is the best score. The aim of this study is to compare the Wang Respiratory Score (WRS) and the Kristjansson Respiratory Score (KRS) in the setting of an emergency room. METHODS: We performed a prospective observational study with 60 infants with bronchiolitis admitted to a paediatric emergency department. For both scores, we assessed inter-rater reliability between two different health professionals (physician and physiotherapist), internal consistency, and correlation with SpO2 testing the intraclass-correlation coefficient (ICC), weighted kappa, Cronbach α coefficient and Spearman tests, respectively. RESULTS: The inter-rater reliability was higher in KRS (ICC 0.79) and the Cronbach α and weighted kappa had similar values in KRS versus WRS. The correlation between the KRS/WRS and SpO2 was poor/moderate upon admission and discharge for the first observer and the second observer. CONCLUSIONS: While the internal consistency was similar in both scores, inter-rater reliability of KRS was higher than WRS, which allows us to conclude that it would have more consistent results when used to assess bronchiolitis' level of severity by health personnel in a busy hospital emergency room.

Maternal Smoking: A Life Course Blood Pressure Determinant?

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP. Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (ß = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (ß = 0.08, 95% CI 0.03 to 0.13 before conception; ß = 0.07, 95%CI 0.02 to 0.12; ß = 0.04, 95%CI -0.02 to 0.10; and ß = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and ß = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children.

BACKGROUND: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. METHODS: Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. RESULTS: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. CONCLUSIONS: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children.

INTRODUCTION: Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children. MATERIALS/METHODS: Cross-sectional evaluation of 309 children aged 8-9 years (161 normal weight, 148 overweight/obese), members of the birth cohort Generation I (Portugal). Anthropometrics (body mass index (BMI), waist-to-height ratio (WHtR) and % body fat mass (%BFM) by bioelectrical impedance analysis), 24-h ambulatory blood pressure monitoring and pulse wave velocity (PWV) were measured. Insulin resistance was estimated by the HOMA index (considering serum fasting glucose and insulin determinations). Serum MPO levels were assessed by immunoenzymatic assay. RESULTS: MPO levels were positively associated with obesity indices (BMI z-score, WHtR and %BFM). Higher MPO levels were associated with higher 24-h and night-time mean arterial pressure, with nondipping and with higher values of insulin resistance. In normal weight children, the endothelial function, as evaluated indirectly by PWV, was an independent predictor of MPO levels. In overweight/obese children, estimated glomerular filtration rate increased significantly across tertiles of MPO (Ptrend = 0·031) and this association held after adjustment for age, sex, neutrophil and monocyte counts and CV risk factors. CONCLUSIONS: Our results reinforce the role of MPO as a risk marker in obesity and related CV morbidities in young children. MPO levels associate with the dipping pattern and PWV and, among overweight/obese children, an association exists between MPO and renal function.

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

Normalization of glomerular filtration rate in obese children.

BACKGROUND: Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. METHODS: This was a cross-sectional study of 313 children aged 8-9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. RESULTS: Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. CONCLUSIONS: Indexing of GFR to BSA calculated from the ideal-rather than actual-body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.

Urinary fibrogenic cytokines ET-1 and TGF-ß1 are associated with urinary angiotensinogen levels in obese children.

BACKGROUND: Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor ß1 (U-TGF-ß1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS). METHODS: The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-ß1 and U-AGT levels were determined by immunoenzymatic methods. RESULTS: Obese children presented with the lowest levels of U-ET-1 and U-TGF-ß1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-ß1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-ß1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-ß1 was associated with U-AGT levels and 24 h-systolic BP. CONCLUSIONS: Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-ß1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury.

Gender and obesity modify the impact of salt intake on blood pressure in children.

BACKGROUND: Most modifiable risk factors for high blood pressure (BP), such as obesity and salt intake, are imprinted in childhood and persist into adulthood. The aim of our study was to evaluate the intake of salt in children and to assess its impact on BP taking into account gender and nutritional status. METHODS: A total of 298 children aged 8-9 years were evaluated in a cross-sectional study. Anthropometric measurements and 24-h ambulatory monitoring were performed, and salt intake was determined by 24-h urinary sodium excretion. RESULTS: The average estimated salt intake among the entire cohort of children enrolled in the study was 6.5 ± 2.2 g/day, and it was significantly higher in boys than in girls (6.8 ± 2.4 vs. 6.1 ± 1.9 g/day, respectively; p = 0.018) and in overweight/obese children than in normal weight children (6.8 ± 2.4 vs. 6.1 ± 2.0 g/day, respectively; p = 0.006). Salt intake exceeded the upper limit of the US Dietary Reference Intake in 72% of children. Daytime systolic BP increased by 1.00 mmHg (95% confidence interval 0.40-1.59) per gram of daily salt intake in overweight/obese boys, but not in normal weight boys or in girls. CONCLUSIONS: Our results demonstrate an extremely high salt intake among 8- to 9-year-old Portuguese children. Higher salt intake was associated with higher systolic BP in boys, specifically in those who were overweight/obese. Longitudinal studies are needed to further evaluate the causal relationship between obesity and high BP and the mechanism by which salt intake modulates this relationship. Nonetheless, based on our results, we urge that dietary salt reduction interventions, along with measures to fight the global epidemic of obesity, be implemented as early in life as possible.

Decreased renal function in overweight and obese prepubertal children.

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.

Obstructive sleep related breathing disorders and cardiometabolic risk factors - A Portuguese birth cohort.

BACKGROUND: Pediatric obstructive sleep related breathing disorders (SRBD) are an important under-diagnosed health problem with associated cardiometabolic comorbidities, demonstrated with polysomnographic studies in selected samples. Our main goal was to assess the prevalence of SRBD in a population-based cohort and to analyze its association with cardiometabolic risk factors, in general and by sex. METHODS: Pediatric Sleep Questionnaire (PSQ) was applied to parents of 7-years-old children evaluated in the birth cohort, Generation XXI. Sex, anthropometrics, blood pressure (BP), lipid profile, glucose, insulin, HOMA-IR, and high-sensitivity C-reactive protein were compared among children with/without SRBD, using Chi-square, Mann-Whitney tests and logistic regression models. RESULTS: A total of 1931 children (51.2 % boys) were included; 17.5 % were overweight and 15.7 % obese. The prevalence of SRBD was 13.4 %, more frequent among boys (15.7 % vs.10.9 %, p = 0.002) and in overweight/obese children (22.0 % vs.13.6 % vs.11.3 % in obese, overweight and normal weight group, respectively, p < 0.001). Children with SRBD had higher systolic BP (107 ± 8 vs.105±9 mmHg; p = 0.001) and lower HDL-cholesterol levels (54 ± 11 vs.56 ± 11 mg/dL; p = 0.04) than children without SRBD. After adjustment for sex, age, birthweight-for-gestational age and maternal age, children with SRBD had higher BMI-z-score, systolic BP, insulin and HOMA-IR levels, and lower HDL-cholesterol, when compared to those without SRBD, but these associations were lost when adjusting to BMI z-score. Analyzing obese children with the same regression model, those with SRBD presented lower HDL-cholesterol than those without SRBD. CONCLUSIONS: Our results identified a male predominance of SRBD in pre-pubertal children and highlighted the potential contribution of SRBD to cardiovascular risk in obese children.

Gender-related differences in cardiometabolic risk factors and oxidative stress among prepubertal children with obesity.

OBJECTIVES: Gender-related differences in oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors were examined in a cross-sectional study involving 313 prepubertal children (8-9 years old) from the generation XXI birth-cohort. METHODS: Anthropometric measurements, cardiometabolic variables, and redox markers were assessed, including plasma and urinary isoprostanes (P-Isop, U-Isop), plasma total antioxidant status (P-TAS), serum myeloperoxidase (MPO), plasma and urinary nitrates and nitrites (P-NOX, U-NOX), and urinary hydrogen peroxide (U-H2O2). RESULTS: Girls showed higher levels of total/non-HDL cholesterol, triglycerides, and insulin resistance (HOMA-IR) compared to boys. Notably, U-H2O2 values were lower in girls. When stratifying by body mass index (BMI) and gender, both girls and boys exhibited higher MPO concentration and U-Isop values. Uric acid concentration was higher in overweight and obese girls than in normal weight girls, while no significant differences were observed among boys across BMI categories. Furthermore, U-NOX values differed only in boys, with higher levels observed in overweight and obese individuals compared to those with normal weight. Multivariate analysis, adjusted for age and BMI z-score, demonstrated inverse associations between U-H2O2 and pulse wave velocity values, as well as between U-NOX and total or non-HDL cholesterol, exclusively in boys. In girls, a positive association between U-Isop and HOMA-IR values was observed. CONCLUSIONS: In conclusion, gender differentially impacts oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors in prepubertal children. Prepubertal girls appear more susceptible to oxidative stress-induced metabolic dysfunction, while in boys, elevated levels of redox and nitric oxide bioavailability markers seem to provide protection against arterial stiffness and lipid homeostasis.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

OBJECTIVES: Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. METHODS: Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1ß, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. RESULTS: There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. CONCLUSIONS: Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

AIMS: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). METHODS: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries. RESULTS: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values). CONCLUSIONS: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center.

INTRODUCTION: Rituximab (RTX) is a therapeutic option in pediatric difficult-to-treat idiopathic nephrotic syndrome (NS). We aimed to assess the efficacy and safety of RTX use in these patients. METHOD: A retrospective study of all patients with idiopathic NS treated with RTX was conducted in a pediatric nephrology division of a tertiary hospital. Demographic, anthropometric, clinical and analytical data were collected prior to treatment and at 6, 12, and 24 months. RESULTS: Sixteen patients were included (11 males), with a median (25th-75th percentile, P25-P75) age at diagnosis of 2 (2.0-2.8) years. Fifteen were steroid-sensitive and 1 was steroid-resistant and sensitive to cyclosporine. The median age at administration of RTX was 10 (6.3-14.0) years. Throughout a median follow-up time of 2.5 (1.0-3.0) years, 6 (37.5%) patients achieved partial remission and 7 (43.8%) had no relapses and were not taking any immunosuppressants at the 24-month follow-up visit. Regarding complications, 1 patient presented persistent hypogammaglobulinemia. Compared with the 12-month period before RTX, there was a decrease in the median number of relapses at 6 and 12 months [3 (3.0-4.0) vs 0 (0-0.8) and 0.50 (0-1.0), respectively; p = 0.001] and in the daily steroids dose (mg/kg/day) at 6, 12, and 24 months [0.29 (0.15-0.67)vs [0.10 (0.07-0.13); p = 0.001], [0.12 (0.05-0.22); p = 0.005] and [0.07(0.04-0.18); p = 0.021]], respectively. There was also a reduction in the median BMI z score at 24 months [2.11 (0.45-3.70) vs. 2.93 (2.01-3.98); p = 0.049]. CONCLUSION: Our results confirm the efficacy and safety of RTX use in pediatric idiopathic NS and highlight its' potential cardiometabolic benefits.

The Association between Childhood Obesity and Cardiovascular Changes in 10 Years Using Special Data Science Analysis.

The increasing prevalence of overweight and obesity is a worldwide problem, with several well-known consequences that might start to develop early in life during childhood. The present research based on data from children that have been followed since birth in a previously established cohort study (Generation XXI, Porto, Portugal), taking advantage of State-of-the-Art (SoA) data science techniques and methods, including Neural Architecture Search (NAS), explainable Artificial Intelligence (XAI), and Deep Learning (DL), aimed to explore the hidden value of data, namely on electrocardiogram (ECG) records performed during follow-up visits. The combination of these techniques allowed us to clarify subtle cardiovascular changes already present at 10 years of age, which are evident from ECG analysis and probably induced by the presence of obesity. The proposed novel combination of new methodologies and techniques is discussed, as well as their applicability in other health domains.