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.

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.

Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

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.

Rituximab therapy for childhood onset idiopathic nephrotic syndrome: experience of a Portuguese tertiary center / Terapia com Rituximabe para síndrome nefrótica idiopática de início na infância: experiência de um centro terciário português

ABSTRACT 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.

Resumo Introdução: Rituximabe (RTX) é uma opção terapêutica na síndrome nefrótica (SN) idiopática pediátrica de difícil tratamento. Visamos avaliar eficácia e segurança do uso de RTX nestes pacientes. Método: Realizou-se estudo retrospectivo de todos os pacientes com SN idiopática tratados com RTX, em uma unidade de nefrologia pediátrica de um hospital terciário. Dados demográficos, antropométricos, clínicos e analíticos foram coletados antes do tratamento e aos 6, 12 e 24 meses. Resultados: Incluímos 16 pacientes (11 do sexo masculino), com idade mediana (percentil 25-75, P25-P75) de 2 (2,0-2,8) anos ao diagnóstico. Quinze eram sensíveis a esteroides, e 1 resistente a esteroides e sensível à ciclosporina.A idade mediana na administração do RTX foi 10 (6,3-14,0) anos. Durante um tempo mediano de acompanhamento de 2,5(1,0-3,0) anos, 6 (37,5%) pacientes alcançaram remissão parcial e 7 (43,8%) não tiveram recidivas e não estavam tomando imunossupressor no acompanhamento aos 24 meses. Quanto às complicações,1 paciente apresentou hipogamaglobulinemia persistente. Comparado ao período de12 meses anterior ao RTX, houve diminuição no número mediano de recidivas em 6 e 12 meses [3 (3,0-4,0) vs 0 (0-0,8) e 0,50 (0-1,0), respectivamente; p = 0,001] e na dose diária de esteroides (mg/kg/dia) aos 6, 12 e 24 meses [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] e [0,07 (0,04-0,18); p = 0,021], respectivamente. Houve também redução na mediana do escore z do IMC aos 24 meses [2,11 (0,45-3,70) vs 2,93 (2,01-3,98);p = 0,049]. Conclusões: Nossos resultados confirmam a eficácia e segurança do uso de RTX em SN idiopática pediátrica, destacando seus potenciais benefícios cardiometabólicos.

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.

Cardiovascular rhythmicity in overweight and obese children.

INTRODUCTION: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. METHODS: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. RESULTS: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. DISCUSSION: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Association between blood pressure and angiotensin-converting enzymes activity in prepubertal children ∗.

OBJECTIVES: Angiotensin-converting enzymes' (ACEs) relationship with blood pressure (BP) during childhood has not been clearly established. We aimed to compare ACE and ACE2 activities between BMI groups in a sample of prepubertal children, and to characterize the association between these enzymes' activities and BP. METHODS: Cross-sectional study of 313 children aged 8-9 years old, included in the birth cohort Generation XXI (Portugal). Anthropometric measurements and 24-h ambulatory BP monitoring were performed. ACE and ACE2 activities were quantified by fluorometric methods. RESULTS: Overweight/obese children demonstrated significantly higher ACE and ACE2 activities, when compared to their normal weight counterparts [median (P25-P75), ACE: 39.48 (30.52-48.97) vs. 42.90 (35.62-47.18) vs. 43.38 (33.49-49.89) mU/ml, P for trend = 0.009; ACE2: 10.41 (7.58-15.47) vs. 21.56 (13.34-29.09) vs. 29.00 (22.91-34.32) pM/min per ml, P for trend < 0.001, in normal weight, overweight and obese children, respectively]. In girls, night-time systolic BP (SBP) and diastolic BP (DBP) increased across tertiles of ACE activity ( P < 0.001 and P  = 0.002, respectively). ACE2 activity was associated with higher night-time SBP and DBP in overweight/obese girls ( P  = 0.037 and P  = 0.048, respectively) and night-time DBP in the BMI z-score girl adjusted model ( P  = 0.018). Median ACE2 levels were significantly higher among nondipper girls (16.7 vs. 11.6 pM/min per ml, P  = 0.009). CONCLUSIONS: Our work shows that obesity is associated with activation of the renin-angiotensin-aldosterone system, with significant increase of ACE and ACE2 activities already in childhood. Also, we report sex differences in the association of ACE and ACE2 activities with BP.

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.

Pediatric kidney transplant and cardiometabolic risk: a cohort study / Transplante renal pediátrico e risco cardiometabólico: um estudo de coorte

Abstract Introduction: Patients with chronic kidney disease (CKD) are known to have increased cardiovascular risk but there are few data on the risk of pediatric kidney transplant recipients. We aimed to assess the impact of pre- and post-transplant overweight on allograft function and to characterize the evolution of several cardiovascular risk variables over time and their impact. Methods: A retrospective analysis of the records of 23 children/adolescents followed at a tertiary center after kidney transplant was conducted. Data on anthropometry and cardiometabolic variables were analyzed before transplant, six and 12 months after the transplant, and at the last follow-up visit. The impact of the variables on allograft function (glomerular filtration rate (GFR)) was estimated by creatinine-based revised Schwartz formula (Cr-eGFR) and was evaluated using nonparametric tests. Results: The 23 patients included in the study had a median age of 6.3 (4.4-10.1) years. Both systolic and diastolic BP z-score values significantly decreased between BMI groups [1.2 (-0.2 - 2.3) vs. 0.3 (-0.4 - 0.6), p=0.027 and 0.8 (-0.4 - 1.3) vs. 0.1 (-0.6 - 0.7), p=0.028, pre-transplant and at the final evaluation, respectively]. During follow-up, GFR values decreased (Cr-GFR: 68.9 (57.7-76.8) vs. 58.6 (48.9-72.9), p=0.033 at 6-months and at the end, respectively). Significant negative correlations between triglycerides and cystatin C-based eGFR (ρ=-0.47, p=0.028) and Cr-Cys-eGFR (ρ=-0.45, p=0.043) at the end of the study were found. Conclusion: Our study showed a high number of overweight children undergoing kidney transplant. A negative correlation between triglycerides and GFR was found, which highlights the importance of managing nutritional status and regular blood lipids evaluation after kidney transplant.

Resumo Introdução: Sabe-se que pacientes com doença renal crônica (DRC) têm maior risco cardiovascular, mas há poucos dados sobre risco de receptores de transplante renal pediátrico. Visamos avaliar o impacto do sobrepeso pré/pós-transplante na função do aloenxerto e caracterizar a evolução de diversas variáveis de risco cardiovascular com o tempo e seus impactos. Métodos: Realizou-se análise retrospectiva dos registros de 23 crianças/adolescentes acompanhados em um centro terciário após transplante renal. Foram analisados dados sobre antropometria e variáveis cardiometabólicas antes do transplante, seis e 12 meses após transplante, e na última consulta de acompanhamento. O impacto das variáveis na função do aloenxerto (taxa de filtração glomerular (TFG)) foi estimado pela fórmula de Schwartz revisada e baseada na creatinina (TFGe-Cr), e avaliado usando testes não paramétricos. Resultados: Os 23 pacientes incluídos no estudo tinham idade média de 6,3 (4,4-10,1) anos. Valores do escore Z das pressões arteriaissistólica e diastólica diminuíram significativamente entre grupos de índice de massa corporal [1,2 (-0,2 - 2,3) vs. 0,3 (-0,4 - 0,6), p=0,027 e 0,8 (-0,4 - 1,3) vs. 0,1 (-0,6 - 0,7), p=0,028, pré-transplante e na avaliação final, respectivamente]. Durante acompanhamento, valores da TFG diminuíram [TFG-Cr: 68,9 (57,7-76,8) vs. 58,6 (48,9-72,9), p=0,033 aos 6 meses e ao final, respectivamente]. Encontramos correlações negativas significativas entre triglicerídeos, TFGe baseada na cistatina C (ρ=-0,47, p=0,028) e TFGe-Cr-Cis (ρ=-0,45, p=0,043) ao final do estudo. Conclusão: Nosso estudo mostrou alto número de crianças com sobrepeso submetidas a transplante renal. Verificou-se correlação negativa entre triglicerídeos e TFG, destacando a importância de controlar o estado nutricional e da avaliação regular dos lipídios sanguíneos após transplante renal.

Pediatric kidney transplant and cardiometabolic risk: a cohort study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are known to have increased cardiovascular risk but there are few data on the risk of pediatric kidney transplant recipients. We aimed to assess the impact of pre- and post-transplant overweight on allograft function and to characterize the evolution of several cardiovascular risk variables over time and their impact. METHODS: A retrospective analysis of the records of 23 children/adolescents followed at a tertiary center after kidney transplant was conducted. Data on anthropometry and cardiometabolic variables were analyzed before transplant, six and 12 months after the transplant, and at the last follow-up visit. The impact of the variables on allograft function (glomerular filtration rate (GFR)) was estimated by creatinine-based revised Schwartz formula (Cr-eGFR) and was evaluated using nonparametric tests. Results: The 23 patients included in the study had a median age of 6.3 (4.4-10.1) years. Both systolic and diastolic BP z-score values significantly decreased between BMI groups [1.2 (-0.2 - 2.3) vs. 0.3 (-0.4 - 0.6), p=0.027 and 0.8 (-0.4 - 1.3) vs. 0.1 (-0.6 - 0.7), p=0.028, pre-transplant and at the final evaluation, respectively]. During follow-up, GFR values decreased (Cr-GFR: 68.9 (57.7-76.8) vs. 58.6 (48.9-72.9), p=0.033 at 6-months and at the end, respectively). Significant negative correlations between triglycerides and cystatin C-based eGFR (ρ=-0.47, p=0.028) and Cr-Cys-eGFR (ρ=-0.45, p=0.043) at the end of the study were found. CONCLUSION: Our study showed a high number of overweight children undergoing kidney transplant. A negative correlation between triglycerides and GFR was found, which highlights the importance of managing nutritional status and regular blood lipids evaluation after kidney transplant.

Determinants of bedwetting trajectories between 4 and 7 years - A birth cohort analysis.

INTRODUCTION: Enuresis is frequent in school-aged children and results from a complex interaction between genetics, biological and psychosocial factors. This study aims to analyze bedwetting trajectories between 4 and 7 years of age and to evaluate the impact of biological and developmental characteristics of the child and sociodemographic factors in those bedwetting trajectories. METHODS: Data from 5433 children from the Generation XXI population-based birth cohort was analyzed. Four bedwetting trajectories were defined: normative (acquired nighttime bladder control at 4 years and no enuresis at 7 years); delayed (no nighttime bladder control at 4 years and no enuresis at 7 years); enuresis (no nighttime bladder control at 4 years and enuresis at 7 years); and secondary enuresis (acquired nighttime bladder control at 4 years and enuresis at 7 years). Multinomial logistic regression models were fitted to test the association between biological and developmental characteristics of the child and sociodemographic factors with bedwetting trajectories. RESULTS: At the age of 4 years, 36.5% of children had bedwetting (8.1% infrequently and 28.4% frequently) and at the age of 7 years, 11.0% had enuresis (5.8% infrequently and 5.2% frequently). Of the 4-year-old children who were infrequent bedwetters, 14.0% had enuresis at 7 years, while among frequent bedwetters, 30.2% had enuresis at 7 years. Regarding bedwetting trajectories, 26.8% of children were classified in the delayed trajectory, 9.7% in the enuresis trajectory and 1.3% were in the secondary enuresis trajectory. Children with developmental disorders presented an increased risk of being in enuresis trajectory (OR = 1.47, 95% CI 1.15-1.88) than children without developmental disorders. Living in overcrowded houses (OR = 1.60, 95% CI 1.12-2.30), growing up in families with low household income (OR = 1.27, 95% CI 1.03-1.57) and an orphan of one parent (OR = 3.19, 95% CI 1.18-8.64) presented higher odds of being in the enuresis trajectory than in the normative trajectory. Having a sibling both before the age of 4 years and between the ages of 4 and 7 years was associated with delayed trajectory (OR = 1.55, 95% CI 1.16-2.07) and with enuresis (OR = 1.53, 95% CI 1.01-2.33), when compared with children without siblings born at that time. CONCLUSION: Both developmental disorders and sociodemographic factors seem to be important determinants of bedwetting trajectories. Further studies are needed to better characterize the impact of biological and environmental determinants, on the nighttime bladder control acquisition, to enable timely medical interventions that improve the quality of life of enuretic children.

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center / Síndrome hemolítica urêmica atípica genética em crianças: uma experiência de 20 anos a partir de um centro terciário

Abstract Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years. Methods: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed. Results: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months). Conclusion: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.

Resumo Introdução: A síndrome hemolítica urêmica atípica (SHUa) é um distúrbio raro caracterizado pela tríade de anemia hemolítica microangiopática, trombocitopenia e lesão renal aguda, afetando principalmente crianças em idade pré-escolar. O objetivo deste estudo foi descrever perfil clínico, manejo e desfecho em longo prazo dos pacientes com SHUa genética admitidos em um centro terciário de nefrologia pediátrica durante 20 anos. Métodos: Realizamos análise retrospectiva dos registros clínicos de todos os pacientes com SHUa menores de 18 anos com mutações genéticas identificadas. Revisaram-se dados sobre características clínicas, estudo genético, intervenções terapêuticas e desfechos em longo prazo. Resultados: Incluíram-se cinco casos de SHUa com uma mutação genética identificada; sendo todos casos inaugurais, o mais jovem tendo 4 meses de idade. A mutação no gene do fator H do complemento foi identificada em quatro pacientes. Plasmaférese terapêutica foi realizada para tratamento agudo em 4 pacientes, um dos quais também necessitou terapia renal substitutiva aguda (diálise peritoneal). Todos os pacientes tiveram remissão completa, 2 mais de uma recidiva, mas apenas 1 evoluiu para doença renal crônica durante acompanhamento (mediana (percentil 25°-75°), 136 (43,5-200,5) meses). Conclusão: Em crianças, o prognóstico da função renal parece ser fortemente dependente do histórico genético, sendo crucial realizar estudo genético em todos os casos de SHUa. Em nossa coorte, 2 pacientes apresentaram mutações genéticas não descritas anteriormente. Inovações recentes no campo genético que levaram à identificação de novas mutações conduziram a um melhor entendimento da patogênese SHUa, mas são necessários mais estudos, focando na correlação genótipo-fenótipo, com períodos de acompanhamento mais longos.

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.

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years. METHODS: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed. RESULTS: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months). CONCLUSION: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.

Impact of physical activity on redox status and nitric oxide bioavailability in nonoverweight and overweight/obese prepubertal children.

Nutritional status might contribute to variations induced by physical activity (PA) in redox status biomarkers. We investigated the influence of PA on redox status and nitric oxide (NO) production/metabolism biomarkers in nonoverweight and overweight/obese prepubertal children. We performed a cross-sectional evaluation of 313 children aged 8-9 years (163 nonoverweight, 150 overweight/obese) followed since birth in a cohort study (Generation XXI, Porto, Portugal). Plasma total antioxidant status (P-TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), myeloperoxidase (MPO) and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were assessed, as well as their association with variables of reported PA quantification (categories of PA frequency (>1x/week and ≤1x/week)and continuous PA index (obtained by the sum of points)) in a questionnaire with increasing ranks from sedentary to vigorous activity levels. U-NOx was significantly higher in children who presented higher PA index scores and higher PA frequency. Separately by BMI classes, U-NOx was significantly higher only in nonoverweight children who practiced PA more frequently (p = 0.037). In overweight/obese children, but not in nonoverweight, P-TAS was higher among children with higher PA frequency (p = 0.007). Homeostasis model assessment index (HOMA-IR) was significantly lower in more active overweight/obese children, but no differences were observed in nonoverweight children. In the fully adjusted multivariate linear regression models for P-TAS, in the overweight/obese group, children with higher PA frequency presented higher P-TAS. In the U-NOx models, U-NOx significantly increased with PA index, only in nonoverweight children. Our results provide additional evidence in support of a protective effect of physical activity, in nonoverweight by increasing NO bioavailability and in overweight/obese children by enhancing systemic antioxidant capacity and insulin sensitivity. These results highlight the importance of engaging in regular physical exercise, particularly among overweight/obese children, in which a positive association between oxidant status and cardiometabolic risk markers has been described.

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.