Childhood obesity-related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements.

Childhood obesity jeopardizes a healthy future for our society's children as it is associated with increased cardiovascular morbidity and mortality later on in life. Endothelial dysfunction, the first step in the development of atherosclerosis, is already present in obese children and may well represent a targetable risk factor. Technological advancements in recent years have facilitated noninvasive measurements of endothelial homeostasis in children. Thereby this topic ultimately starts to get the attention it deserves. In this paper, we aim to summarize the latest insights on endothelial dysfunction in childhood obesity. We discuss methodological advancements in peripheral endothelial function measurement and newly identified diagnostic markers of vascular homeostasis. Finally, future challenges and perspectives are set forth on how to efficiently tackle the catastrophic rise in cardiovascular morbidity and mortality that will be inflicted on obese children if they are not treated optimally.

The role of Th17 and Treg responses in the pathogenesis of RSV infection.

The respiratory syncytial virus (RSV) represents the leading cause of viral bronchiolitis and pneumonia in children worldwide and is associated with high morbidity, hospitalization rate, and significant mortality rates. The immune response elicited by RSV is one of the main factors contributing to the pathogenesis of the disease. Two subsets of the cellular immune response, the T helper 17 cell (Th17) and the regulatory T-cell (Treg), and more particularly the balance between these two subsets, might play a significant role in the pathogenesis of the RSV infection. The developmental pathways of Th17 and Treg cells are closely and reciprocally interconnected and plasticity has been demonstrated from Treg toward Th17. During an RSV infection, the functions of both subsets are opposed to one another regarding viral clearance and clinical severity. Th17 and Treg cells offer a promising new view on the pathogenesis of an RSV infection and deserve further exploration.

Ferritin and body mass index predict cardiac dysfunction in female adolescents with anorexia of the restrictive type.

BACKGROUND AND AIM: Decreased left ventricular mass index in anorexia nervosa is amply reported. The aim of this study is to identify non-burdensome predictors of reduced left yentricular mass/height (cLVM) in a cohort of adolescent restrictive anorexic girls. METHODS: This is a retrospective study of all anorexic girls of the restrictive type referred to our tertiary eating disorder unit between September 2002 and December 2012, for somatic assessment of weig ht loss. All subjects fulfilled DMS-IV criteria, without a family history of cardiac or cardiovascular diseases. RESULTS: In all, 283 restrictive anorexic girls (age: 14.63 +/- 1.65 y; body mass index: 15.72 +/- 1.81 kg/m2) were included. Ferritin and body mass index were independent, statistically significant predictors of the corrected left ventricular mass (P <0.05). CONCLUSION: Decreased cLVM is very common in anorexia nervosa of the restrictive type. Two factors predicted decreased cLVM in our population: ferritin and BMI.

Endothelial progenitor cells and endothelial microparticles are independent predictors of endothelial function.

OBJECTIVE: To examine the degree of microvascular endothelial dysfunction in relation to classical cardiovascular risk factors, arterial stiffness, and numbers of circulating endothelial progenitor cells (EPCs) and endothelial microparticles (EMPs), in obese and normal-weight children. STUDY DESIGN: Cross-sectional study with 57 obese (15.2±1.4 years) and 30 normal-weight children (15.4±1.5 years). The principal outcome was microvascular endothelial function measured with peripheral arterial tonometry. Fasting blood samples were taken for biochemical analysis and EMPs (CD31+/CD42b- particles) and EPCs (CD34+/KDR+/CD45dim/- cells) flow cytometry. Characteristics between groups were compared by use of the appropriate independent samples test; a stepwise multiple regression analysis was used to determine independent predictors of microvascular endothelial function. RESULTS: Microvascular endothelial function was significantly impaired in obese children and inversely correlated with body mass index Z scores (r=-0.249; P=.021) and systolic blood pressure (r=-0.307; P=.004). The number of EPCs was significantly lower in obese children and correlated with endothelial function (r=0.250; P=.022), and the number of EMPs was significantly greater in obese children and correlated inversely with endothelial function (r=-0.255; P=.021). Multivariate analysis revealed that systolic blood pressure and numbers of circulating EPCs and EMPs are important determinants of endothelial function. CONCLUSION: Obese children demonstrate impaired endothelial microvascular function, increased arterial stiffness, fewer EPCs, and more EMPs. Besides systolic blood pressure, EPC and EMP counts independently predict the presence of microvascular endothelial dysfunction.

Sleep-disordered breathing and C-reactive protein in obese children and adolescents.

PURPOSE: Sleep-disordered breathing (SDB) is common among overweight and obese children. It is a risk factor for several health complications, including cardiovascular disease. Inflammatory processes leading to endothelial dysfunction are a possible mechanism linking SDB and cardiovascular disease. Elevated C-reactive protein (CRP) is a risk factor for cardiovascular disease and is independently correlated with obstructive sleep apnea syndrome (OSAS) in adults. Our goal is to evaluate the relationship between CRP and OSAS in overweight and obese children and adolescents. METHODS: One hundred and twenty children were prospectively studied (85 without OSAS, 20 mild OSAS, 15 moderate-to-severe OSAS). All subjects underwent polysomnography, and a blood sample was taken to determine CRP levels. RESULTS: No significant differences were found in CRP between subjects with or without OSAS, and no correlations were found between CRP and OSAS severity, despite the relationship between CRP and BMI (r = 0.21, p = 0.015) and between CRP and fat mass (r = 0.31, p < 0.001). CONCLUSION: These results suggest that CRP levels are correlated with the level of obesity but are not influenced by SDB in obese children and adolescents; hence, this in contrast to that in adult population.

Erythema ab igne in an adolescent with anorexia nervosa.

OBJECTIVE: A rare skin lesion, erythema ab igne (EAI) is presented, in an adolescent female with anorexia nervosa. METHOD: Clinical records of this patient were compared with a pubmed search about EAI in patients with an eating disorder. RESULTS: The patient presented with localized, spider-like, erythematous and hyperpigmented skin lesions on the lower abdomen and on both thighs. Repetitive exposure to heating pads can induce reticular and macular hyperpigmentation with telangiectases without squamation. Strict avoidance of heat is advised, because there is no effective treatment. DISCUSSION: EAI is described in patients with an eating disorder. Facing an increased pain threshold, prolonged heat exposure to treat a general feeling of cold, can induce this dermatosis.

Position paper--HPV and the primary prevention of cancer; improving vaccine uptake by paediatricians.

A large proportion of sexually active adults are infected with the human papillomaviruses (HPVs). Although largely asymptomatic, some types of HPVs (HPV-16, HPV-18) which infect the genitalia are known to cause cancers, including cervical cancer. Cervical cancer is an important public health concern and is the second most clinically important cancer to breast cancer in women aged 15-44 years. Until recently, cervical cancer strategies focussed on screening. However, as adolescents become sexually active at a much younger age, the focus is on the use of vaccination as an effective measure to prevent progression of HPV infection to cancer. HPV is also involved in the aetiology of cancers of the anus, vagina, vulva and penis as well as genital warts and laryngeal papillomatosis in young children. Primary prevention through vaccination is now possible in Europe using either the quadrivalent HPV vaccine, Gardasil® (Sanofi Pasteur MSD), or the bivalent HPV vaccine, Cervarix® (GSK), which are both highly immunogenic, with their effects persisting for at least 5 years. HPV vaccines are well tolerated, with serious vaccine-related events occurring in less than 0.1% of patients for both vaccines. Here, we review the possibilities for utilising vaccination programmes alongside current cervical cancer screening in comprehensive cervical cancer prevention programmes. The European Academy of Paediatrics Scientific Working Group on Vaccination concluded that the use of HPV vaccines will have a significant impact in primary prevention of cancers and other HPV-related disease.

Visceral leishmaniasis in a child infected with the human immunodeficiency virus in a non-endemic region.

We reported the case of a boy who fled from Chechnya to Belgium. He was diagnosed with a human immune deficiency virus (HIV)/Visceral leishmaniasis (VL) coinfection. In both countries, the prevalence of HIV-infected children is low and VL is not endemic. Migration of people results in confrontation with diseases that are not frequent in the countries of destination and becomes a challenge for pediatricians.

Two unusual pediatric cases of dilutional hyponatremia.

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na(+)] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Pericardial effusions in adolescent girls with anorexia nervosa: clinical course and risk factors.

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8-17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between >or= 0.35-2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI or= 25% and IGF-1-level

Medical end-of-life decisions: experiences and attitudes of Belgian pediatric intensive care nurses.

OBJECTIVE: To investigate Belgian pediatric intensive care nurses' involvement in and attitudes toward medical end-of-life decisions with a possible or certain life-shortening effect. METHODS: Questionnaires were distributed to 141 nurses working in 5 of the 7 pediatric intensive care units in Belgium. Nurses were asked to recall the last child in their care whose treatment involved an end-of-life decision and to describe anonymously their involvement in the decision. Attitudes were ascertained by means of statements and a Likert scale. RESULTS: Questionnaires were completed by 89 nurses (63%). During the preceding 2 years, 76 (85%) had cared for at least 1 child for whom a medical end-of-life decision had been made. Nurses were involved in initiating the decision in 17% of cases, participated in decision making in 50%, and played a role in carrying out the decision in 90%. Only 6% of nurses found it always ethically wrong to hasten the death of a child by administering lethal drugs; most nurses (78%) reported they were prepared to cooperate in administering life-ending drugs in some cases. Most (89%) favored adapting the law, making life termination of children legally possible in certain cases. CONCLUSIONS: Belgian pediatric intensive care nurses are often involved in carrying out medical end-of-life decisions, including administration of life-ending drugs, whereas their participation in decision making is more limited. Most think that the current euthanasia law should be extended to minors so that administering life-ending drugs would be possible for terminally ill children in specific circumstances.

Acute retroperitoneal hemorrhage and shock as presenting signs of neuroblastoma in an infant.

Adrenal hemorrhage after the neonatal period is rare. It most often occurs with coagulation disorders or child abuse. Spontaneous bleeding within an adrenal neuroblastoma has been described, but acute massive hemorrhage is exceptional. We describe a case of neuroblastoma of the adrenal gland presenting with acute life-threatening abdominal hemorrhage.

A new challenge for Europe: introducing a pediatric quadrivalent vaccine for measles, mumps, rubella, and varicella.

BACKGROUND: Varicella is often considered to be a benign disease of childhood. In fact, varicella is associated with serious complications and mortality even among healthy individuals. DISCUSSION: Although the course of varicella can be uncomplicated, it can also be associated with serious complications such as pneumonia, fluid and electrolyte disturbances, skin and soft tissue infections and central nervous system disturbances. Worldwide studies have confirmed the high frequency of disease as well as the resultant morbidity, mortality and medical resource use. A quadrivalent vaccine is now available in certain countries to protect against measles, mumps, rubella and varicella (MMRV). Countries that have initiated routine vaccination pro- grams have reported substantial reductions in morbidity and mortality as well as improved health outcomes. The MMRV vaccine facilitates coverage against all four diseases, and would be expected to improve compliance as well as coverage of varicella. CONCLUSIONS: Universal vaccination programs with MMRV should be considered as a way to reduce the medical and economic impact of varicella. The MMRV vaccine provides a means to achieve universal coverage.

Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections.

Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). POLR3A and POLR3C encode subunits of RNA polymerase III. Leukocytes from all 4 patients tested exhibited poor IFN induction in response to synthetic or VZV-derived DNA. Moreover, leukocytes from 3 of the patients displayed defective IFN production upon VZV infection and reduced control of VZV replication. These phenotypes were rescued by transduction with relevant WT alleles. This work demonstrates that monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity.

Medical end-of-life decisions in neonates and infants in Flanders.

BACKGROUND: Paediatricians are increasingly confronted with end-of-life decisions in critically ill neonates and infants. Little is known about the frequency and characteristics of end-of-life decisions in this population, nor about the relation with clinical and patients' characteristics. METHODS: A death-certificate study was done for all deaths of neonates and infants in the whole of Flanders over a 12 month period (August, 1999, to July, 2000). We sent an anonymous questionnaire by mail to the attending physician for each of the 292 children who died under the age of 1 year. Information on patients was obtained from national registers. An attitude study was done for all physicians who attended at least one death during the study period. FINDINGS: 253 (87%) of the 292 questionnaires were returned, and 121 (69%) of the 175 physicians involved completed the attitude questions. An end-of-life decision was possible in 194 (77%; 95% CI 70.4-82.4) of the 253 deaths studied, and such a decision was made in 143 cases (57%; 48.9-64.0). Lethal drugs were administered in 15 cases among 117 early neonatal deaths and in two cases among 77 later deaths (13%vs 3%; p=0.018). The attitude study showed that 95 (79%; 70.1-85.5) of the 121 physicians thought that their professional duty sometimes includes the prevention of unnecessary suffering by hastening death and 69 (58%; 48.1-66.5) of 120 supported legalisation of life termination in some cases. INTERPRETATION: Death of neonates and infants is commonly preceded by an end-of-life decision. The type of decision varied substantially according to the age of the child. Most physicians favour legalisation of the use of lethal drugs in some cases.

The use of drugs with a life-shortening effect in end-of-life care in neonates and infants.

OBJECTIVE: The purpose was to describe the use of drugs with a possible or certain life-shortening effect in end-of-life care in infants and to evaluate the possibly lethal effect. DESIGN: For 292/298 deaths of live born infants (<1 year), in a 1-year period (between 1 August 1999 and 31 July 2000) in Flanders, Belgium, the attending physician could be identified and was sent an anonymous questionnaire. The questionnaires relating to deaths directly preceded by the administration of drugs were reviewed by a multi-disciplinary panel. RESULTS: The response rate was 86.6% (253/292). In 57 cases (22.5%), drugs were administered directly before death. In 17/57 cases, the physician explicitly intended to hasten death. In 16/17 cases information about the drug(s) was available: opioids were administered in 14, a muscle relaxant in 5 and potassium chloride in 3 cases. In 13 cases where the lethal effect could be evaluated, the panel judged that the drugs were effective in hastening death in 10 cases. In most cases the estimated life-shortening was <24 h. In 40/57 cases the physician administered drugs to alleviate pain and/or symptoms, taking into account a possible life-shortening effect without explicitly intending it. Opioids were administered in all 30 cases where information about the drug(s) was supplied. In 13 cases the lethal effect could be evaluated, and in 6 cases the panel judged that the drugs had hastened death. CONCLUSIONS: When life-shortening was explicitly intended, (dosages of) drugs were likely to be lethal. Drugs administered also clearly hastened death in some cases where life-shortening was not explicitly intended.

Diet, exercise, and endothelial function in obese adolescents.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is the first, although reversible, sign of atherosclerosis and is present in obese adolescents. The primary end point of this study was to investigate the influence of a multicomponent treatment on microvascular function. Additional objectives and end points were a reduced BMI SD score, improvements in body composition, exercise capacity, and cardiovascular risk factors, an increase in endothelial progenitor cells (EPCs), and a decrease in endothelial microparticles (EMPs). METHODS: We used a quasi-randomized study with 2 cohorts of obese adolescents: an intervention group (n = 33; 15.4 ± 1.5 years, 24 girls and 9 boys) treated residentially with supervised diet and exercise and a usual care group (n = 28; 15.1 ± 1.2 years, 22 girls and 6 boys), treated ambulantly. Changes in body mass, body composition, cardiorespiratory fitness, microvascular endothelial function, and circulating EPCs and EMPs were evaluated after 5 months and at the end of the 10-month program. RESULTS: Residential intervention decreased BMI and body fat percentage, whereas it increased exercise capacity (P < .001 after 5 and 10 months). Microvascular endothelial function also improved in the intervention group (P = .04 at 10 months; + 0.59 ± 0.20 compared with + 0.01 ± 0.12 arbitrary units). Furthermore, intervention produced a significant reduction in traditional cardiovascular risk factors, including high-sensitivity C-reactive protein (P = .012 at 10 months). EPCs were increased after 5 months (P = .01), and EMPs decreased after 10 months (P = .004). CONCLUSIONS: A treatment regimen consisting of supervised diet and exercise training was effective in improving multiple adolescent obesity-related end points.