Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study.

BACKGROUND: To determine the clinical presentation, current treatment and outcome of children with nonbacterial inflammatory bone disease. METHODS: Retrospective multicenter study of patients entered into the Swiss Pediatric Rheumatology Working Group registry with a diagnosis of chronic nonbacterial osteomyelitis (CNO) and synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome. The charts were reviewed for informations about disease presentation, treatment, course and outcome. RESULTS: Forty-one children (31 girls and 10 boys) from 6 pediatric hospitals in Switzerland diagnosed between 1995 and 2010 were included in the study. The diagnosis was multifocal CNO (n = 33), unifocal CNO (n = 4) and SAPHO syndrome (n = 4). Mean age at onset of CNO was 9.5 years (range 1.4-15.6) and mean follow-up time was 52 months (range 6-156 months). Most patients (n = 27) had a chronic persistent disease course (>6 months), 8 patients had a course with one or more relapses and 6 patients had only one episode of CNO. Forty nine percent had received at least one course of antibiotics. In 57% treatment with nonsteroidal anti-inflammatory drugs (NSAID) was sufficient to control the disease. Twelve out of 16 children with NSAID failure subsequently received corticosteroids, methotrexate, TNF α inhibitors, bisphosphonates or a combination of these drugs. CONCLUSIONS: In a multicenter cohort of 41 children 22% started with unifocal lesion with a significant diagnostic delay. A higher proportion presented with chronic persistent disease than with a recurrent form. An osteomyelitis in the pelvic region is significantly associated with other features of juvenile spondylarthritis.

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.

Peer imitation in children : imitators show communicative attitude only when they copy "effect-less" actions

This field study assesses children's relational attitude when they imitate other children. We observe that 3.7- to 5.4-years-old children show communicative attitude toward the model when they reproduce "effect-less" actions, but not when they copy target actions.

Renal function can be impaired in children with primary hyperoxaluria type 3.

BACKGROUND: Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are believed to present with a less severe phenotype than those with PH1 and PH2, but the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aim of this study was to report our experience with PH3. METHODS: Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after the presence of mutations in the alanine-glyoxylate aminotransferase gene had been ruled out. Clinical, biochemical and genetic data of the seven patients identified with HOGA1 mutations were subsequently retrospectively reviewed. RESULTS: Among the seven patients identified with HOGA1 mutations the median onset of clinical symptoms was 1.8 (range 0.4-9.8) years. Five patients initially presented with urolithiasis, and two other patients presented with urinary tract infection. All patients experienced persistent hyperoxaluria. Seven mutations were found in HOGA1, including two previously unreported ones, c.834 + 1G > T and c.3G > A. At last follow-up, two patients had impaired renal function based on estimated glomerular filtration rates (GFRs) of 77 and 83 mL/min per 1.73 m(2), respectively. CONCLUSIONS: We found that the GFR was significantly impaired in two of our seven patients with PH3 diagnosed during childhood. This finding is in contrast to the early-impaired renal function in PH1 and PH2 and appears to refute to preliminary reassuring data on renal function in PH3.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

The predictive value of preoperative B-type natriuretic peptide in children undergoing cardiac surgery

Introduction: B-type natriuretic peptide (BNP) is a biomarker of myocardial stress. In children, the value of preoperative BNP on postoperative outcome is unclear. The aim of this study was to determine the predictive value of preoperative NT-proBNP on postoperative outcome in children after congenital heart surgery. Results: Ninety-seven patients were included in the study with a median age of 3.3 years [0.7-5.2]. Preoperative median NT-proBNP was 412 pg/ml [164-1309]. NT-proBNP was above the P95 reference value for age in 56 patients (58%). Preoperative NT-proBNP was significantly higher in patients who had mechanical ventilation duration of more than 2 days (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) and who stayed more than 6 days in the pediatric intensive care unit (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). However, preoperative NT-proBNP was not significantly higher in patients with an increased inotropic score, a prolonged cardiopulmonary bypass time or an increased surgical risk category. Conclusions: An elevated preoperative NT-proBNP reflects hemodynamic status and cardiac dysfunction, and therefore is a valuable adjunct in predicting a complicated postoperative course. ___________________________________ Introduction: Le peptide natriurétique type B (BNP) est un marqueur reflétant le stress myocardique. Dans la population pédiatrique, la signification des valeurs préopératoire de BNP, en particulier sur l'évolution postopératoire, n'est pas clairement établie. Le but de l'étude est de déterminer la valeur prédictive de la partie NT sérique du BNP (NT-proBNP) sur l'évolution post opératoire d'enfants porteur d'une cardiopathie congénitale et ayant eu une chirurgie cardiaque. Résultats: Nonante-sept enfants ont été inclus dans l'étude, avec un âge médian de 3.3 ans [0.7-5.2]. La valeur médiane du NT-proBNP préopératoire était de 412 pg/ml [164-1309]. Le NT-proBNP préopératoire était supérieur au P95 des valeurs de référence pour l'âge chez 56 patients (58%). Le NT-proBNP préopératoire était significativement plus élevé chez les patients ayant eu plus de deux jours de ventilation mécanique dans la période postopératoire (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) et ayant été hospitalisés plus de 6 jours dans l'unité de soins intensifs pédiatrique (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). Par contre, le NT-proBNP préopératoire n'était pas significativement plus élevé chez les patients ayant eu un score d'inotrope élevé pendant leur hospitalisation aux soins intensifs, un temps de circulation extracorporelle prolongé ou ayant subi une chirurgie avec un risque chirurgical élevé. Conclusions: Un NT-proBNP sérique élevé en préopératoire reflète l'importance du stress myocardique induit par l'hémodynamique et la dysfonction myocardique, il est un marqueur qui permet d'améliorer l'identification des patients à risque d'avoir une évolution post opératoire compliquée.

Cardiovascular dysfunction in children conceived by assisted reproductive technologies.

Epidemiological studies demonstrate a relationship between pathological events during foetal development and future cardiovascular risk and the term 'foetal programming of cardiovascular disease' has been coined to describe this phenomenon. The use of assisted reproductive technologies (ARTs) is growing exponentially and 2-5% of children are now born by this procedure. Emerging evidence indicates that ART represents a novel important example of foetal programming. Assisted reproductive technology may modify the cardiovascular phenotype in two ways: (i) ART involves manipulation of the early embryo which is exquisitely sensitive to environmental insults. In line with this concern, ART alters vascular and cardiac function in children and studies in mice show that ART alters the cardiovascular phenotype by epigenetic alterations related to suboptimal culture conditions. (ii) Assisted reproductive technology markedly increases the risk of foetal insults that augment cardiovascular risk in naturally conceived individuals and are expected to have similar consequences in the ART population. Given the young age of the ART population, it will take another 20-30 years before data on cardiovascular endpoints will be available. What is clear already, however, is that ART emerges as an important cardiovascular risk factor. This insight requires us to revise notions on ART's long-term safety and to engage on a debate on its future. There is an urgent need to better understand the mechanisms underpinning ART-induced alteration of the cardiovascular phenotype, improve the procedure and its long-term safety, and, while awaiting this aim, not to abandon medicine's fundamental principle of doing no harm (to future children) and use ART parsimoniously.

Commotion cérébrale chez l'enfant et l'adolescent sportif [Concussion in children and adolescents during sports].

Concussion, a frequent injury in sports, is rarely evoked and often trivialized in children and teenagers. Knowledge of the diverse symptoms and signs to seek for is essential to an appropriate and secure management. The initial treatment relies on cognitive and physical rest followed by a progressive return to school and subsequently sport activities. The aim of this article is to review an injury whose prognosis is generally favourable, but whose rare complications can prove dramatic.

Improvement of allocentric spatial memory resolution in children from 2 to 4 years of age

Allocentric spatial memory, the memory for locations coded in relation to objects comprising our environment, is a fundamental component of episodic memory and is dependent on the integrity of the hippocampal formation in adulthood. Previous research from different laboratories reported that basic allocentric spatial memory abilities are reliably observed in children after 2 years of age. Based on work performed in monkeys and rats, we had proposed that the functional maturation of direct entorhinal cortex projections to the CA1 field of the hippocampus might underlie the emergence of basic allocentric spatial memory. We also proposed that the protracted development of the dentate gyrus and its projections to the CA3 field of the hippocampus might underlie the development of high-resolution allocentric spatial memory capacities, based on the essential contribution of these structures to the process known as pattern separation. Here, we present an experiment designed to assess the development of spatial pattern separation capacities and its impact on allocentric spatial memory performance in children from 18 to 48 months of age. We found that: (1) allocentric spatial memory performance improved with age, (2) as compared to younger children, a greater number of children older than 36 months advanced to the final stage requiring the highest degree of spatial resolution, and (3) children that failed at different stages exhibited difficulties in discriminating locations that required higher spatial resolution abilities. These results are consistent with the hypothesis that improvements in human spatial memory performance might be linked to improvements in pattern separation capacities.

Laparoscopic technique to perform a true Stamm gastrostomy in children.

PURPOSE: A surgical gastrostomy is mandatory in cases where a PEG is not feasible. Various minimally invasive techniques have been described, but many involve unusable materials in small children and/or have risk of disunion. We describe a technique for true Stamm gastrostomy performed by laparoscopy (LSG) with a purse string suture and four points of attachment onto the wall. METHOD: We reviewed 20 children who underwent an LSG from 2010 to 2013. After incision of the skin at the location planned for the gastrostomy, using three 3-5mm ports the stomach is fixed to the wall by three suspension stitches, which are entered and then emerged subcutaneously. A fourth stitch of attachment is used to make an award on the stomach and tie around the gastrostomy tube. RESULTS: Mean age was 4.2years, with 70% aged <2years. All children were malnourished, most often severely. All but two underwent a concomitant fundoplication. Feeding through the gastrostomy started on D0 or D1. Total feeding by gastrostomy was achieved in a mean duration of 2.9day. Mean hospital stay was 4.5days. There was no perioperative complication. Mean follow-up was 14months. Once, the balloon was accidently deflated and reinflated in the wall leading to its necrosis. Five peristomial granulomas were noticed. It was always possible to replace the tube by a gastrostomy device at least 6weeks after surgery. CONCLUSION: This new technique for true Stamm gastrostomy by laparoscopy reproduces exactly the one done by laparotomy, without special equipment. It can be made since the neonatal period, in all the circumstances when a laparoscopy is possible.

Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency.

Adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) is characterized by impaired T-, B- and NK-cell function. Affected children, in addition to early onset of infections, manifest non-immunologic symptoms including pulmonary dysfunction likely attributable to elevated systemic adenosine levels. Lung disease assessment has primarily employed repetitive radiography and effort-dependent functional studies. Through impulse oscillometry (IOS), which is effort-independent, we prospectively obtained objective measures of lung dysfunction in 10 children with ADA-SCID. These results support the use of IOS in the identification and monitoring of lung function abnormalities in children with primary immunodeficiencies.

Efficacy of an eradication schema in case of Pseudomonas aeruginosa primo-infection in children with cystic fibrosis

Introduction: Patients with Cystic fibrosis (CF) are more susceptible to pathogens like P. aeruginosa (PA). PA primo-infection requires particular attention as failure in eradication is associated with accelerated lung deterioration. The main aim of this study is to assess the rate of PA eradication according to our particular protocol with inhaled tobramycin and oral ciprofloxacin, as there is no consensus in the literature on what eradication protocol is optimal. Methods: Retrospective single centre study with data analysis from June 1st 2007 to June 1st 2011 of patients with PA primo-infection exclusively treated by 3 x 28 days of inhaled tobramycin and oral ciprofloxacin for the first and last 21 days. Success in eradication is defined by ≥ 3 negative bacteriologies for 6 months after the beginning of the protocol. If ≥ 1 bacteriology is positive, we consider the eradication as a failure. Results: Out of 41 patients, 18 followed the eradication protocol and were included in our analysis (7 girls (38.9%) and 11 boys (61.1%)). Boys had 12 primo-infections and girls had 8. Among these 20 primo-infections, 16 (80%) had an overall success in eradication and 4 (20%) a failure. There was no significant statistical differences in age between these groups (t-test = 0.07, p = 0.94), nor for FEV1% (t-test = 0.96, p = 0.41) or BMI (t-test = 1.35, p = 0.27). Rate of success was 100% for girls and 66.6% for boys. Conclusion: Our protocol succeeded in an overall eradication rate of 80%, without statistical significant impact on FEV1 % and BMI values. However, there was a sex difference with eradication rates in girls (100%) and boys (66.6%). A sex difference has not yet been reported in the literature. This should be evaluated in further studies.

Potential blindness in children of patients with hereditary bone disease.

Mono- and bi-allelic mutations in the low-density lipoprotein receptor related protein 5 (LRP5) may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or persistent hyperplastic primary vitreous (PHPV). We report on a child affected with PHPV and carrying compound mutations. The father carried the splice mutation and suffered from severe bone fragility since childhood. The mother carried the missense mutation without any clinical manifestations. The genetic diagnosis of their child allowed for appropriate treatment in the father and for the detection of osteopenia in the mother. Mono- and bi-allelic mutations in LRP5 may cause osteopetrosis, autosomal dominant and recessive exudative vitreoretinopathy, juvenile osteoporosis, or PHPV. PHPV is a component of persistent fetal vasculature of the eye, characterized by highly variable expressivity and resulting in a wide spectrum of anterior and/or posterior congenital developmental defects, which may lead to blindness. We evaluated a family diagnosed with PHPV in their only child. The child presented photophobia during the first 3 weeks of life, followed by leukocoria at 2 months of age. Molecular resequencing of NDP, FZD4, and LRP5 was performed in the child and segregation of the observed mutations in the parents. At presentation, fundus examination of the child showed a retrolental mass in the right eye. Ultrasonography revealed retinal detachment in both eyes. Thorough familial analysis revealed that the father suffered from many fractures since childhood without specific fragility bone diagnosis, treatment, or management. The mother was asymptomatic. Molecular analysis in the proband identified two mutations: a c.[2091+2T>C] splice mutation and c.[1682C>T] missense mutation. We report the case of a child affected with PHPV and carrying compound heterozygous LRP5 mutations. This genetic diagnosis allowed the clinical diagnosis of the bone problem to be made in the father, resulting in better management of the family. It also enabled preventive treatment to be prescribed for the mother and accurate genetic counseling to be provided.