Spontaneous resolution of an intrapericardial thrombus as a complication of pericardiocentesis in a neonate.

We present the case of a premature neonate with pericardial effusion secondary to extravasation of total parenteral nutrition from a mispositioned/migrated umbilical venous catheter. Emergency pericardiocentesis was complicated by an intrapericardial thrombus, which was managed conservatively with spontaneous resolution within 24 hours. This case illustrates that the rare complication of an intrapericardial thrombus after pericardiocentesis can be successfully managed conservatively with close monitoring in haemodynamically stable paediatric patients.

Arterial tortuosity in pediatric Loeys-Dietz syndrome patients.

Loeys-Dietz syndrome (LDS) is an autosomal connective tissue disorder commonly presenting with hypertelorism, bifid uvula, aortic aneurysms, and arterial tortuosity. The aim of the present study was to investigate differences in tortuosity index (TI) between genotypes of LDS, possible progression over time and its use as an adjunctive prognostic tool alongside aortic dimensions to aid timely surgical planning in pediatric patients. A retrospective observational study of pediatric LDS patients referred to our center (November 2012-February 2021) was conducted. Using magnetic resonance angiography (MRA) with 3D maximum intensity projection volume-rendered angiogram, arterial TI was measured. Twenty three patients had genetically confirmed LDS with at least one head and neck MRA and 19 had no less than one follow-up MRA available. All patients presented arterial tortuosity. Patients with TGFBR2 variants had greater values of TI compared to patients with TGFB2 variants (p = 0.041). For patients who did not undergo surgery (n = 18), z-scores at the level of the sinus of Valsalva showed a significant correlation with vertebral TI (rs = 0.547). There was one death during follow-up. This study demonstrates that patients with LDS and TGFBR2 variants have greater values of TI than patients with TGFB2 variants and that greatest values of TI are associated with increased aortic root z-scores. Furthermore, as TI decreases over time, less frequent neuroimaging follow-up can be considered. Nevertheless, additional studies are needed to better define more accurate risk stratification and long-term surveillance in these patients.

Self-control training supplementing inpatient multidisciplinary obesity treatment in children and adolescents.

Research points to self-control as a possible mechanism for facilitating health behaviour and weight loss. The dual pathway model underpins the role of strong bottom-up reactivity towards food and weak top-down executive functions in obesity. Despite flourishing lab studies on attention bias modification or inhibition trainings, relatively few focused on training both processes to improve self-control in children and adolescents in inpatient multidisciplinary obesity treatment (MOT). Being part of the WELCOME project, this study investigated the effectiveness of Brain Fitness training (using the Dot Probe and Go/No-Go) as an adjunct to inpatient MOT in 131 Belgian children and adolescents. Changes in self-control (performance-based inhibitory control and attention bias as well as self-reported eating behaviour) in the experimental group were compared to sham training. Multiple Imputation was used to handle missing data. Inhibitory control and external eating improved over time (pre/post/follow-up), but we found no evidence for a significant interaction between time and condition. Future research should pay more attention to the role of individual variability in baseline self-control, sham training, and ecological validity of self-control training to improve real-life health behaviour and treatment perspectives for children and adolescents with weight problems.

Severe dilated cardiomyopathy as an unusual clinical presentation in an infant with sialidosis type II.

We report a unique case of an infant with a severe dilated cardiomyopathy as the clinical presentation of sialidosis type II (OMIM 256550), a rare autosomal recessive inherited lysosomal storage disease that is characterized by partial or complete deficiency of α-neuraminidase, following mutations in the gene neuraminidase 1 (NEU1), located on the short arm of chromosome 6 (6p21.3). Accumulation of metabolic intermediates leads to severe morbidity, especially myoclonus, gait disturbances, cherry-red macules with secondary loss of visual acuity, impaired color vision and night blindness, and sometimes additional neurological findings such as seizures. Dilated cardiomyopathies are characterized by dilation and impaired contraction of the left or both ventricles, whereas most of the metabolic cardiomyopathies are hypertrophic forms appearing with diastolic dysfunction and, in case of lysosomal storage diseases, often associated with valvular thickening and prolapse. Cardiac manifestations in systemic storage disorders are common although rarely described in mucolipidoses. In mucolipidosis type 2 or I-cell disease only three cases were presented with severe dilated cardiomyopathy and endocardial fibroelastosis in infancy, as opposed to sialidosis type II, by which to the best of our knowledge no presentation of dilated cardiomyopathy was previously reported in literature.

The SIDECAR project: S-IcD registry in European paediatriC and young Adult patients with congenital heaRt defects.

AIMS: Subcutaneous-implantable cardiac defibrillators (S-ICDs) are used increasingly to prevent sudden cardiac death in young patients. This study was set up to gain insight in the indications for S-ICD, possible complications, and their predictors and follow-up results. METHODS AND RESULTS: A multicentre, observational, retrospective, non-randomized, standard-of-care registry on S-ICD outcome in young patients with congenital heart diseases (CHDs), inherited arrhythmias (IAs), idiopathic ventricular fibrillation (IVF), and cardiomyopathies (CMPs). Anthropometry was registered as well as implantation technique, mid-term device-related complications, and incidence of appropriate/inappropriate shocks (IASs). Data are reported as median (interquartile range) or mean ± standard deviation. Eighty-one patients (47% CMPs, 20% CHD, 21% IVF, and 12% IA), aged 15 (14-17) years, with body mass index (BMI) 21.8 ± 3.8 kg/m2, underwent S-ICD implantation (primary prevention in 59%). This was performed with two-incision technique in 81% and with a subcutaneous pocket in 59%. Shock and conditional zones were programmed at 250 (200-250) and 210 (180-240) b.p.m., respectively. No intraoperative complications occurred. Follow up was 19 (6-35) months: no defibrillation failure occurred, 17% of patients received appropriate shocks, 13% of patients received IAS (supraventricular tachycardias 40%, T-wave oversensing 40%, and non-cardiac oversensing 20%). Reprogramming, proper drug therapy, and surgical revision avoided further IAS. Complications requiring surgical revision occurred in 9% of patients, with higher risks in patients with three-incision procedures [hazard ratio (HR) 4.3, 95% confidence interval (95% CI) 0.5-34, P = 0.038] and BMI < 20 (HR 5.1, 95% CI 1-24, P = 0.031). CONCLUSION: This multicentre European paediatric registry showed good S-ICD efficacy and safety in young patients. Newer implantation techniques and BMI > 20 showed better outcome.

The Predictive Value of Adipokines and Metabolic Risk Factors for Dropouts and Treatment Outcomes in Children With Obesity Treated in a Pediatric Rehabilitation Center.

Background: Inpatient pediatric obesity treatments are highly effective, although dropouts and weight regain threaten long-term results. Preliminary data indicate that leptin, adiponectin, and cardiometabolic comorbidities might predict treatment outcomes. Previous studies have mainly focused on the individual role of adipokines and comorbidities, which is counterintuitive, as these risk factors tend to cluster. This study aimed to predict the dropouts and treatment outcomes by pre-treatment patient characteristics extended with cardiometabolic comorbidities (individually and in total), leptin, and adiponectin. Methods: Children aged 8-18 years were assessed before, immediately after and 6 months after a 12-month inpatient obesity treatment. Anthropometric data were collected at each visit. Pre-treatment lipid profiles; glucose, insulin, leptin, and adiponectin levels; and blood pressure were measured. The treatment outcome was evaluated by the change in body mass index (BMI) standard deviation score (SDS) corrected for age and sex. Results: We recruited 144 children with a mean age of 14.3 ± 2.2 years and a mean BMI of 36.7 ± 6.2 kg/m2 corresponding to 2.7 ± 0.4 BMI SDS. The 57 patients who dropped out during treatment and the 44 patients who dropped out during aftercare had a higher pre-treatment BMI compared to the patients who completed the treatment (mean BMI, 38.3 ± 6.8 kg/m2 vs 35.7 ± 5.5 kg/m2) and those who completed aftercare (mean BMI, 34.6 ± 5.3 kg/m2 vs 37.7 ± 6.3 kg/m2) (all p<0.05). Additionally, aftercare attenders were younger than non-attenders (mean age, 13.4 ± 2.3 years vs 14.9 ± 2.0, p<0.05).Patients lost on average 1.0 ± 0.4 SDS during treatment and regained 0.4 ± 0.3 SDS post-treatment corresponding to regain of 43 ± 27% (calculated as the increase in BMI SDS post-treatment over the BMI SDS lost during treatment). A higher BMI and more comorbidities inversely predicted BMI SDS reduction in linear regression (all p<0.05).The absolute BMI SDS increase after returning home was predicted by pre-treatment leptin and systolic blood pressure, whereas the post-treatment BMI SDS regain was predicted by pre-treatment age, leptin, and adiponectin levels (all p<0.05) in multivariate linear regressions. Conclusion: Patients who need treatment the most are at increased risk for dropouts and weight regain, emphasizing the urgent need for interventions to reduce dropout and support inpatients after discharge. Furthermore, this study is the first to report that pre-treatment leptin and adiponectin levels predict post-treatment BMI SDS regain, requiring further research.

The impact of obstructive sleep apnea on endothelial function during weight loss in an obese pediatric population.

BACKGROUND: Childhood obesity is an increasing problem with substantial comorbidities such as obstructive sleep apnea (OSA) and increased cardiovascular morbidity. Endothelial dysfunction is an underlying mechanism related to both obesity and OSA. RESEARCH QUESTION: To investigate the effect of weight loss on endothelial function and OSA in obese children and to determine whether a change in endothelial function can be linked to an improvement in OSA. METHODS: Obese children between 8 and 18 years of age were recruited while entering a 12-month inpatient weight loss program. Patients were followed at 3 study visits: baseline, after 10 months of weight loss, and 6 months after ending the program (18 months). Anthropometry and endothelial function (EndoPAT) were determined at all study visits. At baseline, sleep screening with a portable device (ApneaLink) was performed. This was repeated after 10 months if OSA was diagnosed at baseline. RESULTS: At baseline, 130 children were included, of which 87 had OSA (67%). Seventy-two patients attended the follow-up visit at 10 months, and 28 patients attended the follow-up visit at 18 months. The BMI z-score decreased after 10 months (from 2.7 (1.4-3.4) to 1.7 (0.5-2.7); p < 0.001) and remained stable at 18 months. Endothelial function improved significantly after weight loss, evidenced by a shorter time to peak response (TPR) and higher reactive hyperemia index (p = 0.02 and p < 0.001), and remained improved after 18 months (p < 0.001 and p = 0.007). After 10 months of weight loss, 10 patients had residual OSA. These patients had a higher TPR at 10 months (225 (75-285)s) than those without OSA (135 (45-225)s) and patients with a normalized sleep study (105 (45-285)s; p = 0.02). Linear mixed models showed that more severe OSA was associated with a worse TPR at baseline and less improvement after weight loss. CONCLUSION: Weight loss improves endothelial function in an obese pediatric population. However, even after weight loss, endothelial function improved less in the presence of OSA.

The effect of weight regain on cardiometabolic health in children with obesity: A systematic review of clinical studies.

AIMS: Children with obesity are treated by a lifestyle intervention to obtain weight loss. Nevertheless, weight regain often occurs. This systematic review examines the effect of weight regain on cardiometabolic health and summarizes these results in the metabolic syndrome prevalence as integrated endpoint. DATA SYNTHESIS: A literature search was performed in PubMed and Web of Science. Studies were selected if they included participants aged <18 years with obesity and presented data before and after weight loss and after weight regain hereby reporting minimally 1 cardiovascular risk factor at every assessment. After screening, nine articles remained. Generally, the diastolic BP re-increased after weight regain, whereas for systolic BP a sustained result for 6 months was reported with an increase during longer follow-up. No significant changes in fasting glucose were reported after weight regain compared to baseline. Regarding triglycerides, a complete weight regain re-increased the lowered values to baseline, whereas a partial regain resulted in a sustained decrease in triglycerides in 2 studies and an increase to intermediate levels in 1 paper. HDL-cholesterol only rose several months after initiating treatment. Hs-CRP remained lowered for a longer period than the moment where the weight loss nadir was achieved. CONCLUSION: Research on weight regain and cardiometabolic health in children with obesity is scarce. No convincing evidence was found for a worsening of the cardiometabolic profile after weight regain. Some benefits even persisted despite weight recovery. Subsequently, the metabolic syndrome prevalence seems temporarily lowered after weight loss, despite weight regain.

Childhood onset nexilin dilated cardiomyopathy: A heterozygous and a homozygous case.

Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy (DCM) usually presenting around 50 years of age. We describe an asymptomatic boy who had transient DCM at 3 months of age, that resolved by 4 months. Presently, at 11 years of age, he has normal cardiac function with signs of mild DCM on cardiac MRI. Genetic diagnostics revealed a paternally derived, heterozygous 1949_1951del class 4 variant in NEXN. His father had mild DCM with mildly reduced systolic function. The second patient presented with fetal hydrops at 33 weeks gestation requiring emergency caesarian delivery. Postnatally she required ventilation and continuous inotropic support for left ventricle systolic dysfunction. She died after 2 weeks when therapy was withdrawn. Homozygous c.1174C > T,p.(R392*) class 4 variants in the NEXN gene were found via WES. Microscopic investigation showed endomyocardial fibroelastosis. Her parents, both heterozygous carriers, had normal cardiac function and the family history was normal. These patients show a new clinical spectrum of pediatric cardiac disease seen in heterozygous and homozygous NEXN variants, ranging from mild, transient DCM to a severe, fatal neonatal DCM. These patients support the inclusion of the NEXN gene in the investigation of pediatric patients with DCM, even in cases with transient DCM.

Improving Treatment Outcome in Children With Obesity by an Online Self-Control Training: A Randomized Controlled Trial.

Background: Currently available treatment programs for children with obesity only have modest long-term results, which is (at least partially) due to the poorer self-control observed within this population. The present trial aimed to determine whether an online self-control training, training inhibition, and redirecting attentional bias, can improve the short- and long-term treatment outcome of (in- or outpatient) child obesity treatment programs. Methods: In this double-blind multi-center randomized controlled trial (RCT), participants aged 8-18 years with obesity were allocated in a 1:1 ratio to receive an online self-control or sham training added to their in- or outpatient multidisciplinary obesity treatment (MOT) program. The primary endpoint was BMI SDS. Data were analyzed by linear mixed models and the main interactions of interest were randomization by time and randomization by number of sessions, as the latter was cumulatively expressed and therefore represents the effect of increasing dose over time. Results: One hundred forty-four inpatient (mean age 14.3 ± 2.2 years, BMI 2.7 ± 0.4 SDS, 42% male) and 115 outpatient children (mean age 11.9 ± 2.1 years, BMI 2.4 ± 0.4 SDS, 45% male) were included. Children's BMI lowered significantly during treatment in both the in- and outpatient treatment centers, p < 0.001. In a mixed model with BMI as dependent variable, randomization by time was non-significant, but the number of self-control trainings (randomization * number of sessions) interacted significantly with setting and with age (p = 0.002 and p = 0.047), indicating a potential effect in younger inpatient residents. Indeed, a subgroup analysis on 22 inpatient children of 8-12 years found a benefit of the number of self-control trainings on BMI (p = 0.026). Conclusions: The present trial found no benefit of the self-control training in the entire study population, however a subgroup of young, inpatient participants potentially benefited.

The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity.

BACKGROUND: Childhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels. METHODS: Children and adolescents with obesity aged 8-18 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA. RESULTS: A total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng/ml, p = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (p = 0.03, p = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng/ml, p = 0.7) in our population. CONCLUSION: BDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.

Comparison of bioimpedance spectroscopy and dual energy X-ray absorptiometry for assessing body composition changes in obese children during weight loss.

BACKGROUND: Obesity and age influence the reliability of dual energy X-ray absorptiometry scanning (DEXA) and bioimpedance spectroscopy (BIS). Both are used in clinical settings, but have not been compared for measurements in obese children. We compared DEXA and BIS for evaluating body composition and inherent changes in obese children before and after a 10-month weight loss programme. METHODS: DEXA and BIS were used to evaluate 130 patients at baseline and 75 at follow-up. We tested agreement between the two techniques using Bland-Altman plots and proportional bias using Passing-Bablok regressions. RESULTS: The Bland-Altman plots showed wide agreement limits before and after weight loss and when monitoring longitudinal changes. At baseline, the Passing-Bablok regressions revealed a proportional bias for all body compartments. After significant weight loss no proportional bias was found for fat mass and percentage, although BIS systematically underestimated fat mass by 2.9 kg. Longitudinally, no proportional bias was found in the measured changes of absolute fat, fat-free mass and fat-free percentage between both methods, although BIS systematically underestimated fat and fat-free mass by 2.6 and 0.7 kg, respectively. CONCLUSION: While BIS and DEXA are not interchangeable at baseline, the agreement between the two improved after significant weight loss. Proportional changes in fat mass, fat-free mass and fat-free percentage were similar for both techniques. BIS is a viable alternative to DEXA for future paediatric obesity studies measuring treatment effect at group levels, but is not superior to DEXA and cannot be used for monitoring individual changes due to wide limits of agreement.

Epidermal growth factor and its influencing variables in healthy children and adults.

BACKGROUND & OBJECTIVE: Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations. METHODS: Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology. RESULTS: Serum EGF was inversely correlated with age (r = -0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF. CONCLUSIONS: This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.

WELCOME: improving WEight controL and CO-Morbidities in children with obesity via Executive function training: study protocol for a randomized controlled trial.

BACKGROUND: Obesity is a widespread problem that not only leads to medical and psychological diseases in adults, but also in children and adolescents at an early stage in life. Because of its global burden on both the individual and society, it is necessary to develop effective evidence-based treatments. Current "Multidisciplinary Obesity Treatments" (MOT) already provide significant weight loss, but still leave room for more long-lasting improvements. In this protocol paper, we outline the research goals of the WELCOME trial, based on a substantial proof of concept. METHODS: In this Randomized Controlled Trial (RCT) - conducted in both an inpatient and two outpatient treatment settings - existing MOT will be supplemented with an Executive Function (EF) training and compare effects on various parameters in an experimental versus an active control group of obese youngsters (8-18 years old). WELCOME aims to (a) train youngsters' executive functions to facilitate effects on weight loss, psychological and medical comorbidities, (b) to enhance the long-term effects by continuing the training in the daily home context with booster sessions, and (c) to investigate its effects until a 6-month follow-up. In comparison to the active control group, better progress is expected in the experimental group on following variables: weight, psychological comorbidities (unhealthy eating behavior, internalizing symptoms, impaired self-esteem) and medical comorbidities (metabolic syndromes, endothelia dysfunction, tonsillar hypertrophy and sleep obstruction). DISCUSSION: It is stated that this EF-training for enhancing self-control abilities is necessary for a long-lasting effect of childhood obesity treatment interventions. TRIAL REGISTRATION: The Study Procotol was registered on 10/05/2017 (n° ISRCTN14722584 ).

Impact of Lifestyle Intervention on HDL-Induced eNOS Activation and Cholesterol Efflux Capacity in Obese Adolescent.

Background. Endothelial dysfunction occurs in obese children and adolescent and is regarded as a key step in the development of atherosclerosis. Important components for the development of endothelial dysfunction are reduced activity of endothelial nitric oxide synthase (eNOS) and an increase in cholesterol deposition in the vessel wall, due to reduced reverse cholesterol transport (RCT) activity. High density lipoprotein (HDL) exhibits antiatherosclerotic properties including modulation of eNOS activity and cholesterol efflux capacity. Lifestyle intervention programs can modify endothelial dysfunction in obese adolescents, but their impact on HDL-mediated eNOS activation and RCT is unknown so far. Methods. Obese adolescents (15 ± 1 years, BMI > 35 kg/m2) where randomized either to an intervention group (IG, n = 8; restricted diet and exercise) or to a usual care group (UC, n = 8). At the beginning and after 10 months of treatment HDL-mediated eNOS phosphorylation and cholesterol efflux capacity were evaluated. Results. Ten months of treatment resulted in a substantial weight loss (-31%), an improvement of endothelial function, and an increase in HDL-mediated eNOS-Ser1177 phosphorylation and RCT. A correlation between change in eNOS-Ser1177 phosphorylation or RCT and change in endothelial function was noted. Conclusion. A structured lifestyle intervention program improves antiatherosclerotic HDL functions, thereby positively influencing endothelial function.