Search

Different pain types may be encoded in different brain circuits. Here, we examine similarities and differences in brain processing of visceral and somatic pain. We analyze data from seven fMRI studies (N = 165) and five types of pain and discomfort (esophageal, gastric, and rectal distension, cutaneous thermal stimulation, and vulvar pressure) to establish and validate generalizable pain representations. We first evaluate an established multivariate brain measure, the Neurologic Pain Signature (NPS), as a common nociceptive pain system across pain types. Then, we develop a multivariate classifier to distinguish visceral from somatic pain. The NPS responds robustly in 98% of participants across pain types, correlates with perceived intensity of visceral pain and discomfort, and shows specificity to pain when compared with cognitive and affective conditions from twelve additional studies (N = 180). Pre-defined signatures for non-pain negative affect do not respond to visceral pain. The visceral versus the somatic classifier reliably distinguishes somatic (thermal) from visceral (rectal) stimulation in both cross-validation and independent cohorts. Other pain types reflect mixtures of somatic and visceral patterns. These results validate the NPS as measuring a common core nociceptive pain system across pain types, and provide a new classifier for visceral versus somatic pain., Whether the brain processes different types of pain similarly or differently remains unknown. The authors show that an established neurologic pain signature responds to five different types of visceral and somatic pain; they also develop a new classifier that reliably discriminates between both pain modalities.

Beta thalassemia major (βTM) is the most common inherited hemoglobinopathy. Management essentially focuses on preventing and treating complications. Conventional treatment is based on a regular blood transfusion program, and chelation therapy. Management essentially focuses on preventing and treating complications. Severe complications of βTM are very rarely seen in children in Europe. In the context of the migrant crisis, pediatricians will be confronted with the challenge of managing severe complicated βTM. We report the case of 2 Syrian 10-year-old twin girls who arrived to France with numerous and severe complications of βTM: hemochromatosis, alloimmunization, hypopituitarism, osteopenia… Their clinical management, which led to successful vital and functional improvement, is reported in this article.

Enteral nutrition (EN) allows adequate nutritional intake in children for whom oral intake is impossible, insufficient or unsafe. With maturation and health improvements, most children ameliorate oral skills and become able to eat orally, therefore weaning from EN becomes a therapeutic goal. No recommendations currently exist on tube weaning, and practices vary widely between centres. With this report, the French Network of Rare Digestive Diseases (FIMATHO) and the French-Speaking Group of Paediatric Hepatology, Gastroenterology and Nutrition (GFHGNP) aim to develop uniform clinical practice recommendations for weaning children from EN. A multidisciplinary working group (WG) encompassing paediatricians, paediatric gastroenterologists, speech-language therapists, psychologists, dietitians and occupational therapists, was formed in June 2018. A systematic literature search was performed on those published from January 1, 1998, to April 30, 2020, using MEDLINE. After several rounds of e-discussions, relevant items for paediatric tube weaning were identified, and recommendations were developed, discussed and finalized. The WG members voted on each recommendation using a nominal voting technique. Expert opinion was applied to support the recommendations where no high-quality studies were available.

International audience; Objectives: Supplementing diet with citrulline has proved an efficient means of preserving nitrogen balance and improving nutritional status after massive intestinal resection. The aim of this study was to model the action of citrulline in gut-resected rats using a dose-ranging study focused on skeletal muscle nitrogen homeostasis.Methods: Forty-six rats were randomly assigned to one of the following groups: citrulline 0.5 g.kg.d(-1) (n = 9), citrulline 1 g.kg.d(-1) (n = 7), citrulline 2.5 g.kg.d(-1) (n = 8), citrulline 5 g.kg.d(-1) (n = 8), control (n = 6), and sham (n = 8). The sham group underwent transection and the other groups underwent resection of 80% of the small intestine. All rats were then fed enteral nutrition (EN; all diets were isocaloric and isonitrogenous). After 10 d, the rats were sacrificed to measure and analyze animal weight; duodenum, jejunum, and ileum weight; and muscle trophicity. Protein fractional synthesis rate (FSR) and mammalian target of rapamycin complex (mTORC)1 activation were measured in the tibialis muscle.Results: There was a significant dose-dependent association between rat weight and citrulline dose up to 2.5 g.kg.d(-1) (P = 0.004). There was a significant improvement in tibialis weight correlated to plasma citrulline. Net protein FSR in the tibialis tended to be greater after resection and tended to return to baseline after citrulline supplementation. Citrulline supplementation significantly decreased the activated phosphorylated forms of S6 K1 (P = 0.003) and S6 RP (P = 0.003), with a significant positive association between myofibrillar FSR and activation of S6 K1 (r = 0.614; P = 0.02) and S6 RP (r = 0.601; P = 0.023). Jejunum weight was significantly positively correlated with plasma citrulline (r = 0.319; P = 0.0345).Conclusion: Citrulline promotes body weight gain, preserves muscle trophicity, and enhances intestinal adaptation in a dose-dependent manner in a model of resected rats.

Objectives: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. Methods: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = –1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. Results: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P

Primary immunodeficiencies are inherited disorders, which may be revealed in the context of autoimmune hemolytic anemia (AIHA). We report the case of a girl presenting with an enterovirus-related AIHA. Despite being in complete remission for her anemia after treatment, the initial CD4/CD8 lymphopenia dramatically worsened with time. Its sole clinical presentation was generalized verrucosis. Cellular quantitative and functional immunodeficiency was evidenced but no known molecular defect was identified despite extensive workup. This unlabeled profound naive T-lymphopenia was cured by bone marrow transplantation. No similar case was ever described in the scientific literature. Patients with AIHA and/or generalized verrucosis should be screened for primary immunodeficiency, before initiating any immunomodulatory treatment.

Background The use and optimal duration of treatment with nebulized hypertonic saline (HS) in infants hospitalized for acute bronchiolitis is unclear. The objective was to compare the efficacy of 1 versus 3 days of nebulized 3% HS at 72 h of treatment. We conducted a blinded non-inferiority randomized controlled trial including infants aged less than 12 months old, hospitalized for a moderate bronchiolitis. Methods Nebulisations of 3% HS for 1 day were followed by either the continuation of 3% HS (HS3d group) or switched to 0.9% normal isotonic saline (HS1d group) for 2 days Randomization was performed according to a predefined list with a 1:1 ratio, obtained with a random generator number with blocks.. Main outcome was mean Wang clinical severity score (CSS) after 72 h of treatment. Results One hundred sixteen infants (HS1d n = 59 and HS3d n = 57), were included over two epidemic seasons from 2014 to 2016, but recruitement did not reach the planned sample size. The difference for the Wang CSS score in the HS3d vs HS1d group was 0.71 [IC 90% 0.1; 1.3], above the precluded value of 0.4 set in the protocol defining the non-inferiority of shorter treatment duration. Clinical remission was more rapidly obtained in the HS3d than in HS1d (2.3 ± 1.6 vs 2.9 ± 1.4 days, p = 0.04), with a non-significant tendency for less need of nutritional support and supplemental oxygen in HS3d group. Clinical worsening and treatment intolerance were similar in the 2 groups. Conclusions Despite being underpowered, results seem not to be in favour of reducing the duration of nebulised HS treatment from 3 to 1 day in acute moderate bronchiolitis. Trial registration Clinical trials NCT 02538458, October 2014.

International audience; Aim: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants.Methods: We report secondary outcomes from a controlled, double‐blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha‐1 antitrypsin and calprotectin, and maturity, namely elastase‐1.Results: Faecal alpha‐1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 ± 1.32 vs 1.82 ± 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1‐Q3] of 296 [136‐565] μg/g stools in both groups combined at study day 21). Faecal elastase‐1 was lower in the new fortifier than control fortifier group (202.5 ± 1.6 vs 257.7 ± 1.5 μg/g stools, P = .016).Conclusion: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised.

International audience; OBJECTIVES: The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product. METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events. RESULTS: We recruited 136 patients ages 9.8 +/- 4.4 years at baseline. Mean body mass index z score was -1.0 +/- 1.8; mean height z score was -1.1 +/- 1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children. CONCLUSIONS: This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.

International audience; BACKGROUND AND AIMS: Abetalipoproteinemia (ABL) is a rare recessive monogenic disease due to MTTP (microsomal triglyceride transfer protein) mutations leading to the absence of plasma apoB-containing lipoproteins. Here we characterize a new ABL case with usual clinical phenotype, hypocholesterolemia, hypotriglyceridemia but normal serum apolipoprotein B48 (apoB48) and red blood cell vitamin E concentrations. METHODS: Histology and MTP activity measurements were performed on intestinal biopsies. Mutations in MTTP were identified by Sanger sequencing, quantitative digital droplet and long-range PCR. Functional consequences of the variants were studied in vitro using a minigene splicing assay, measurement of MTP activity and apoB48 secretion. RESULTS: Intestinal steatosis and the absence of measurable lipid transfer activity in intestinal protein extract supported the diagnosis of ABL. A novel MTTP c.1868G\textgreaterT variant inherited from the patient's father was identified. This variant gives rise to three mRNA transcripts: one normally spliced, found at a low frequency in intestinal biopsy, carrying the p.(Arg623Leu) missense variant, producing in vitro 65% of normal MTP activity and apoB48 secretion, and two abnormally spliced transcripts resulting in a non-functional MTP protein. Digital droplet PCR and long-range sequencing revealed a previously described c.1067+1217\₁141del allele inherited from the mother, removing exon 10. Thus, the patient is compound heterozygous for two dysfunctional MTTP alleles. The p.(Arg623Leu) variant may maintain residual secretion of apoB48. CONCLUSIONS: Complex cases of primary dyslipidemia require the use of a cascade of different methodologies to establish the diagnosis in patients with non-classical biological phenotypes and provide better knowledge on the regulation of lipid metabolism.

International audience; A central aim of cognitive neuroscience is to identify how different mental processes are represented in brain activity. The medial frontal cortex (MFC), which includes multiple functionally distinct cortical areas in the superior frontal and cingulate gyri 1 , is one brain region that has been linked to diverse psychological domains, i.e., sets of related psychological states with different adaptive functions 2. Clearly, different areas within MFC encode different functions, but there is a striking convergence of overlapping functions across domains in several 'hub' areas, particularly the anterior midcingulate cortex (aMCC 3). Research across species has linked activity in aMCC with multiple functions, including cognitive control 4,5 , reward-based learning and decision making 6-9 , somatic pain 10,11 , and processing of emotional 12,13 and social information 14,15. In fact, this area responds to such a variety of tasks, and so many underlying functions have been proposed to explain its responses, that it has been described as a "Rorschach test" and understanding it a "holy grail for many cognitive neuroscientists. " 16 Theories of aMCC function often explain the numerous signals in this area as components of an underlying process that operates across domains. Candidate processes have included conflict monitoring 4 , adaptive control (i.e., control processes broadly engaged by negative affect and nociception 17), cognitive effort 18 , valuation of actions 19 and control 20 , and detecting threats to survival 21 , among others. These models have value because they offer integrative explanations for aMCC engagement across multiple domains. However, measuring brain activity across domains with functional MRI (fMRI) glosses over a potential multiplicity of different local neural circuits with distinct functions 22,23. Electrophysiological and optogenetic studies of likely homologs of human aMCC provide evidence for distinct subpopulations of neurons with different functional properties 6,8,24. Recent evidence suggests that multivariate patterns of fMRI activity can, in some cases, identify representations distributed across subpopulations of cells, including identifying functionally dissociable patterns within aMCC associated with different tasks 25,26. Thus, unified accounts of aMCC function make predictions about the similarity of multivariate brain representations across domains that have not been adequately tested. If a set of domains activate representations of a single underlying process, then engaging these representations by tasks from these domain sets should produce similar patterns of brain activity in aMCC and other MFC areas. Conversely, if different domains engage an underlying pattern that is specific to each domain and not shared by other domains, this would provide evidence against a common underlying process. Here we test these predictions using a construct-validation approach grounded in psychometric theory. We investigated three constructs that engage MFC: pain, cognitive control, and negative emotion (see Methods). We sampled human fMRI data from 18 The medial frontal cortex, including anterior midcingulate cortex, has been linked to multiple psychological domains, including cognitive control, pain, and emotion. However, it is unclear whether this region encodes representations of these domains that are generalizable across studies and subdomains. Additionally, if there are generalizable representations, do they reflect a single underlying process shared across domains or multiple domain-specific processes? We decomposed multivariate patterns of functional MRI activity from 270 participants across 18 studies into study-specific, subdomain-specific, and domain-specific components and identified latent multivariate representations that generalized across subdomains but were specific to each domain. Pain representations were localized to anterior midcingulate cortex, negative emotion representations to ventromedial prefrontal cortex, and cognitive control representations to portions of the dorsal midcingulate. These findings provide evidence for medial frontal cortex representations that generalize across studies and subdomains but are specific to distinct psychological domains rather than reducible to a single underlying process.

Spinal cord compression in Wilms’ tumor (WT) is an extremely rare event that can have a very poor prognosis if not taken care of rapidly. Most cases reported in the literature involve widely metastatic patient with bone or paraspinal metastases or occasionally intradural metastasis. Here, we present the case of a 3-year-old girl of WT confirmed by biopsy, with spinal cord compression due to the direct contiguous spread of a tumor through 2 vertebral foramina. Abdominal ultrasonography and magnetic resonance imaging performed for an abdominal mass revealed a large heterogeneous tumor near the upper pole of the left kidney. A nodular infiltration extended through the T11-L1 and L1-L2 neural foramina, forming an intraspinal mass that compressed the spinal cord. Major paresthesia subsequently occurred, requiring urgent treatment with corticosteroids and chemotherapy. The evolution was rapidly satisfying. After six courses of chemotherapy, a left nephrectomy was performed. Macroscopic examination identified a large tumor attached to the kidney without renal infiltration. Microscopical examination concluded to a nephroblastoma with regressive changes, of intermediate risk. Evolution at 6 months is satisfactory, with no neurological deficit. The histological aspect of the tumor and the clinical outcome suggest that she had an extrarenal WT that spread through the vertebral foramina and was secondarily attached to the kidney.

International audience; The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases.

International audience; Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12 ± 3 in patients vs 4 ± 1 in controls on the Center for Epidemiologic Studies-Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 ± 84 ms(2) vs 1607 ± 1032 ms(2) , p = 0.043; LF 455 ± 153 ms(2) vs 1629 ± 585 ms(2) , p = 0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43 ± 3 mmHg vs 30 ± 2 mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS.

Background: Transcutaneous bilirubin (TcB) is a validated test for systematic screening of neonatal hyperbilirubinemia and monitoring term and near-term infants under phototherapy. Objectives: To evaluate TcB diagnostic accuracy for very preterm neonates. Methods: Total serum bilirubin (TSB) and TcB measurements were performed prospectively in a multicenter sample of newborns Results: Altogether, 481 measurements were analyzed in 167 preterm patients. Mean GA was 27.6 ± 1.6 weeks. The rates of newborns requiring phototherapy were 52% in the first 3 days, 16% from the 4th to the 7th day, and 2% during the second week. Diagnostic performance was similar among babies with or without phototherapy. TcB sensitivity decreased over time from 100% (93.9-100.0) to 50% (1.3-98.7). Specificity showed an inverse evolution from 14.8% (7.0-26.2) to 80.7% (72.2-89.2). The best performance was that of negative predictive values which varied from 95.5 to 100.0. False negatives were rare throughout the study (0.8% of measurements). In a multivariate analysis, the only factor significantly influencing discordance between TcB and TSB was postnatal age. We did not find any impact of GA and skin color. Conclusion: Among very preterm babies, TcB measurements might be useful for screening for neonatal jaundice in the first 2 weeks of life. In case of a TcB value below the phototherapy threshold, invasive TSB quantification could be unnecessary, with potential avoidance of blood drawing.

The historical view of the renin-angiotensin system (RAS) is that of an endocrine hypertensive system that is controlled by renin and mediated via the action of angiotensin II on its type 1 receptor. Numerous new angiotensins (Ang) and receptors have been described, the majority being hypotensive and natriuretic, namely Ang-(1-7) and its receptor rMas. Renin and its precursor (pro-renin) can bind their common receptor. In addition to the production of Ang II, this receptor triggers intracellular effects. Given the control of renin production by intracellular calcium, calcium homeostasis is of particular importance. Ang-(1-12), which is not controlled by renin, is converted to several different angiotensin peptides and is a new pathway of the RAS. Local RAS enzymes produce or transform the different hyper- or hypotensive angiotensin within vessels and organs, but also in blood through circulating forms of the enzymes. In the kidney, a powerful local vascular RAS allows for the independence of renal vascularization from systemic control. Moreover, the kidney also contains an independent urinary RAS, which counterbalances the systemic RAS and coordinates proximal and distal sodium reabsorption. The systemic and local effects of renal RAS cannot be analyzed without taking into account the antagonistic effect of renalase. Our concept of RAS needs to evolve to take into account its dual potentiality (hyper- or hypotensive).

Summary Background Nutritional therapy has an established role as induction therapy in paediatric Crohn’s disease. However, compliance is the main difficulty and may be greatly influenced by the administration route. Aim To analyse the efficiency of exclusive nutrition to induce remission in children with Crohn’s disease comparing fractionated oral vs. continuous enteral feeding. Methods The medical records of 106 patients treated by exclusive nutritional therapy [Modulen IBD (R)] by either oral or continuous enteral route were reviewed retrospectively. Comparative analyses of remission rates, changes in anthropometry, Paediatric Crohn’s disease Activity Index (PCDAI), laboratory indices and compliance rates were performed. Results On exclusive enteral nutrition, at 8 weeks, 34/45 patients achieved remission in the oral group (75% on intention-to-treat analysis) and 52/61 (85%) in the enteral nutrition group (P = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (P

Background: Oral challenges are required to establish the persistence or resolution of IgE-mediated cow’s milk allergy (CMA). Determining the appropriate timing for challenging is the main difficulty. The benefit of the basophil activation test (BAT) in predicting a child’s reaction to the oral challenge was evaluated and compared to the specific IgE and skin prick tests’ (SPT) results. Methods: One hundred and twelve consecutive children with CMA admitted for an oral challenge to reassess their allergy were included. Allergen-induced basophil activation was detected as a CD63-upregulation by flow cytometry. Results: Thirty-six children (32%) had a positive oral challenge. The percentage of activated basophils in patients with a positive challenge (mean = 20.9; SD = 18.8) was significantly higher than that of patients with a negative challenge (mean = 3.9; SD = 9.8, P < 0.0001), and was well correlated with the eliciting dose of cow’s milk (P < 0.0001). The BAT had an efficiency of 90%, a sensitivity of 91%, a specificity of 90%, and positive and negative predictive values of 81% and 96% in detecting persistently allergic patients. The area under the ROC curve was 0.866. These scores were higher than those obtained with SPT and IgE values, whichever positivity cut-point was chosen. Referring to a decisional algorithm combining BAT, specific IgE and SPT allowed the correct identification of 94% of patients as tolerant or persistently allergic to cow’s milk proteins (CMP) in our cohort. Conclusion: The BAT could be a valuable tool in the management of paediatric CMA in addition to specific IgE quantification and SPT, by contributing in determining whether an oral challenge can safely be undertaken.

Objectives: Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy. Materials and Methods: A cross-sectional study conducted in 26 HIV-1 vertically infected children ages 8 to 18 years old. Liver function was assessed with standard serum biochemical markers, FibroTest, ActiTest, SteatoTest, Forns index, aspartate aminotransferase to platelet ratio index, ultrasound, and Fibroscan. Results: Nineteen (>60%) children had signs of liver affection on at least 1 of the test results: 13 (50%) had elevated liver enzymes, 15 (63%), 8 (33%), 5 (21%), and 5 (21%) had abnormal FibroTest, ActiTest, Forns index, and aspartate aminotransferase to platelet ratio index results, respectively. Four children (17%) had mild liver steatosis on ultrasound. Fibroscan measures were significantly higher in patients than in age-matched healthy children. Patients with elevated Fibroscan measures also had significantly higher FibroTest results. Age, HIV stage N in the Centers for Disease Control and Prevention classification and exposure duration to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs were the main risk factors for hepatotoxicity. Conclusions: More than half of our population of HIV-infected children had biological and/or radiological signs of liver affection. Regular follow-up of liver function is necessary in these patients, which is now possible with noninvasive procedures.

Background Femoral shaft fractures occur very frequently in children, and their prognosis usually is good. Nonoperative treatment is the gold standard for children under 6 years because of the excellent bony union and the remodelling qualities. Purpose The aim of this study was to compare two orthopaedic therapeutic methods: skin traction versus immediate reduction. Materials and methods The study involved 35 children, divided into two groups: in group 1, treatment consisted of skin traction for 21 days followed by hip spica casting; in group 2, an immediate reduction with early hip spica casting was performed. The ranges of motion, the delay before weight bearing, the hospitalisation duration and the required amount of painkillers were recorded. We compared initial shortening, axial, sagittal and rotational alignment, and femoral length discrepancy. We calculated the injured femoral diaphysal overgrowth and correlated it to the fracture type and location and to the initial shortening. Economical variables were also studied. Results The mean overgrowth was 8.9 mm in group 1 and 8.5 mm in group 2. Three years after the trauma, length discrepancy was 4 mm in group 1 and 1 mm in group 2. Hip spica casting leads to significant reductions in weight-bearing delay, hospitalisation duration and pain. The cost of treatment with skin traction was four times higher (24,472 euros) than that of immediate reduction (6,384 euros). Discussion Our results are in accordance with the literature. The femoral overgrowth was proportional to the initial shortening. Masculine gender, an oblique fracture and injury of the lower third of the femur were associated with the greatest femoral overgrowth. During the first year of follow-up, the femoral length discrepancy hardly varied after immediate reduction (4 mm), whereas the overgrowth reached 6 mm after skin traction. Overall, immediate hip spica casting leads to significant reductions in weight-bearing delay, hospitalisation duration, complications and costs, while having similar clinical results as traction.

Intervertebral disk calcification is a rare childhood disease. The etiology of disk calcification in children remains unclear. We report three cases of children with cervical disk calcification. Their clinical manifestations are very different. The first patient mainly had a neurological deficiency. The second had neck pain and muscular deficit of the left musculus deltoideus. The third had isolated strong neck pain. By presenting these three cases, we want to recall the different symptoms that correspond to this disease and discuss the decisions to be made in regard to radiological investigation and treatment. Healing takes place spontaneously after several days, and the calcifications disappears after about 6 months after a stage of fragmentation. Conservative treatment by immobilization of the spine and analgesic therapy are sufficient. Operative treatment should be reserved for severe radicular pain or for significant and persistent sensorimotor deficits from either root or spinal cord compression.

Postural deformities are frequent in neonates. The moulded baby syndrome (MBS) comprises one or more of the following disorders: plagiocephaly, torticollis, congenital scoliosis, pelvic obliquity, adduction contracture of a hip and/or malpositions of the knees or feet. We analysed the incidence of MBS in healthy neonates and identified the risk factors of its composing elements. One thousand and one healthy neonates were examined on the second or third day of life by the same paediatrician. Familial, obstetrical, perinatal history and putative risk factors for postural deformities were collected. Families of newborns with a torticollis or plagiocephaly were given positioning advice and the outcome was evaluated by a phone survey 2 months later. MBS was detected in 107 neonates (10.7%): 97 plagiocephalies or torticollis, 25 congenital scoliosis or pelvic obliquities, and 13 malpositions of the knees or feet. We identified risk factors related to the mother (age: OR = 1.39, parity: OR = 0.643), to the obstetrical history (preterm labour: OR = 1.65, oligoamnios: OR = 10.179, breech presentation: OR = 2.746, pregnancy toxaemia: OR = 3.773, instrumental delivery: OR = 6.028) and to the newborn (male gender: OR = 1.982, birth length: OR = 1.196). The initial plagiocephaly or torticollis improved in 77% of infants after 2 months of stimulation and positioning measures. Paediatricians should be alert regarding the frequent but subtle MBS postural deformities and give positioning advice to the parents. A neonate of male gender or greater birth length, with an older primiparous mother, a history of preterm labour, oligoamnios or pregnancy toxaemia, a breech presentation or an assisted delivery is more likely to have MBS.

Extension supra-condylar fracture of the humerus is a most common fracture in children. Several treatment regimens have been used in the treatment of displaced supra-condylar humeral fractures. A prospective study was performed including 67 children presenting a displaced supra-condylar humeral fracture. We uniformly treated them by closed reduction under general anaesthesia with fluoroscopic control and two parallel lateral pinnings. The criteria for inclusion were a supra-condylar humeral fracture (Gartland type II and type III) with posterior displacement in an infant, or in an adolescent less than 16 years old. According to the Flynn classification, there were 47 excellent results (70%), 15 good (23%), two fair (3%) and three poor (4%), which means 62 good and excellent results (93%). This percentage fell to 61 and 27% respectively if we considered the humero-ulnar angle. Forearm prono-supination was always normal. Poor results analysis found no relation between them except for the type of the fracture. The humero-ulnar angle seemed to be the pejorative radiological criterion. There was no correlation between type of reduction in AP or lateral X-ray and functional or cosmetic results. Poor fracture reduction induced residual deformity; anatomic reduction is therefore necessary to avoid it.

Background: Despite reports of an increasing incidence of asthma in HIV-infected children, exploration of pulmonary function by spirometry has never been reported in this population in the HAART era. Objective: The aim of this study was to determine the prevalence of spirometric abnormalities in HIV-1 infected children. We conducted a cross-sectional study of pulmonary function tests (PFT) in HIV-1 vertically infected children. Methods: Spirometric values were measured in 17 HIV-1 chronically infected children and compared to matched healthy children. In HIV-1 infected children, the correlations between PFT and the determination of the single breath carbon monoxide diffusing capacity of the lung (TL CO ) and immunological and virological values were assessed. Results: Overall, 11 of the 17 PFT were normal. Four showed mild distal obstruction. Two were considered restrictive. When compared with matched healthy children, the only difference was the FEV1/FVC ratio that was significantly lower in the patients’ group (91.9% of predicted value versus 97.1%, p

BACKGROUND Septic arthritis in childhood is a therapeutic emergency. The authors present their experience using an intermediate technique with the advantages of the percutaneous aspiration irrigation drainage: joint aspiration, irrigation, and declivious drainage. METHODS All children were treated by joint aspiration under fluoroscopic control, large volume irrigation, and declivious nonsuction drainage associated with immobilization and intravenous antibiotics during 8 days to 10 days. The draining system was removed when clinical improvement (namely apyrexia) and the decrease of biological inflammatory response were obtained. A late follow-up phone interview was made for each patient. Fifty-two patients were included in this study, with a mean age of 4.3 years. The most common sites of arthritis were the hip (19 of 52, 36%) and the knee (17 of 52, 32%), but ankle (8 of 52, 15%), shoulder (12%), and elbow (3%) were also involved. RESULT Apyrexia was obtained after a mean period of 2 days. The mean draining duration was 4.5 days. On the last follow-up visit (at 21 months on average; range, 12-56 months), all patients except one were totally painless and had no limitation of physical activity. CONCLUSION Percutaneous aspiration irrigation drainage assured very good results in this study population, with rapid clinical and biological improvement and the absence of long-term sequelae. The advantages of this technique include permanent joint access and control of synovial effusions, with only one general anesthesia and minimal iatrogenic morbidity.

Progressive liver toxicity is a concern in HIV-infected patients. Although liver biopsy remains the gold standard for liver assessment, its invasiveness, sampling errors, variability in interpretation and expense do not make it an ideal routine follow-up exam. During the last decade, new non-invasive tools have been developed for the assessment of hepatic fibrosis in HCV and HIV/HCV co-infected patients.

Screwing of slipped capital femoral epiphysis must prevent its further slipping by prematurely fusing the physis. Whichever material is used, persistent femoral growth has been described, thereby increasing the risk of bone deformation. The objective of this study is to evaluate the residual growth after screwing of slipped capital femoral epiphysis. This study concerned 26 children, among which 13 children have been included, and 13 children excluded because of an incomplete clinical or radiological follow-up, or treatment by another technique. The pathological hip was treated with one screw (in eight cases) or two screws (in five cases). The controlateral hip was fixed with one screw. The different measures were taken on anteroposterior radiographs done the days after surgery, and on the first radiograph on which the growth plate had fused. Growth plate fusion was obtained after an average of 20 months. Each patient had presented a residual growth of at least one hip, thus 85% of the 26 fixed screws. Among the four hips, which did not grow, three were pathological, and were fixed by one screw (in one case) or two screws (in two cases), in a central or medial position. There was not any statistical relationship between the growth persistence and the other studied criteria. These results, proving the growth persistency, suggest that the follow-up must be extremely careful, as the number of threads crossing the growth plate will decrease, with the risk of loss of mechanical stability and reappearance of the femoral epiphysis slippage.

A too-long anterior process of the calcaneus is one of the causes of repeated sprained ankles or painful feet in the child or adolescent that is often ignored and misdiagnosed. Among 31 cases of adolescents having consulted for these symptoms, a too-long anterior process of the calcaneus was discovered on radiographs, and explored in detail with a computed tomography scan or an MRI. The decision for surgical resection was taken considering the discomfort expressed by these children. The intraoperative observation corroborated the radiological findings and permitted a better understanding of the mechanisms responsible for the pain, the repeated sprained ankles and other instabilities. The surgical resection, which is a simple procedure, gave very good results. One must nevertheless be aware of the possible secondary lesions because of repeated sprained ankles: breakage of the lateral ligaments of the ankle and external malleolus nonunion or talus osteochondritis, which can compromise the operation's result, if they are not treated simultaneously.

Osteopontin (OPN) is a multifunctional protein involved in hepatic steatosis, inflammation, fibrosis and cancer progression. However, its role in hepatic injury induced by ischemia-reperfusion (I-R) has not yet been investigated. We show here that hepatic warm ischemia for 45 min followed by reperfusion for 4 h induced the upregulation of the hepatic and systemic level of OPN in mice. Plasma aspartate aminotransferase and alanine aminotransferase levels were strongly increased in Opn(-/-) mice compared with wild-type (Wt) mice after I-R, and histological analysis of the liver revealed a significantly higher incidence of necrosis of hepatocytes. In addition, the expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNFα), interleukin 6 (IL6) and interferon-γ were strongly upregulated in Opn(-/-) mice versus Wt mice after I-R. One explanation for these responses could be the vulnerability of the OPN-deficient hepatocyte. Indeed, the downregulation of OPN in primary and AML12 hepatocytes decreased cell viability in the basal state and sensitized AML12 hepatocytes to cell death induced by oxygen-glucose deprivation and TNFα. Further, the downregulation of OPN in AML12 hepatocytes caused a strong decrease in the expression of anti-apoptotic Bcl2 and in the ATP level. The hepatic expression of Bcl2 also decreased in Opn(-/-) mice versus Wt mice livers after I-R. Another explanation could be the regulation of the macrophage activity by OPN. In RAW macrophages, the downregulation of OPN enhanced iNOS expression in the basal state and sensitized macrophages to inflammatory signals, as evaluated by the upregulation of iNOS, TNFα and IL6 in response to lipopolysaccharide. In conclusion, OPN partially protects from hepatic injury and inflammation induced in this experimental model of liver I-R. This could be due to its ability to partially prevent death of hepatocytes and to limit the production of toxic iNOS-derived NO by macrophages.

L’osteoponti ne (OPN) est une cytokine TH1 impliquee dans l’inflammation hepatique et dans la prevention de la mort hepatocytaire. Nous cherchons a preciser ici son role dans la constitution des lesions hepatiques d’ischemie- reperfusion (IR) normothermique. Methode 45 min d’ischemie chaude partielle puis 4h de reperfusion ont ete realisees chez des souris mâles wild-type(wt) et OPN - knockout (OPN-/-). L’etude des genes a ete faite par RT-PCR. Les taux circulants d’OPN, ASAT, ALAT ont ete mesures par ELISA et biochimie standard. La mort cellulaire a ete evaluee par l’activite caspase3 et l’histologie. Resutats Nous montrons pour la premiere fois que l’IR hepatique induit une up regulation de l’expression genique et du taux circulant d’OPN chez la souris. Les ASAT et ALAT sont augmentes chez les souris OPN-/- versus wt. En histologie,la necrose est majoree. Mais le niveau d’apoptose evalue par l’activite caspase3 est le meme. L’expression des genes de l’inflammation est augmentee chez les souris OPN-/-. Alors que l’OPN freine l’expression d’iNOS dans les macrophages, celle ci est augmentee uniquement dans le foie des souris OPN -/- apres IR. Conclusion Nous montrons qu’OPN pourrait prevenir la necrose et l’inflammation hepatique induites par l’IR en limitant la mort cellulaire et la production de NO.

Introduction: When oral rehydration fails, nasogastric (NG) rehydration is the second-line recommended therapy in pediatric acute gastroenteritis (AGE), since it has been shown to be as effective as intravenous (IV) rehydration. However, NG rehydration is underused in France due to parental and physician's reluctance. We aimed to identify risk factors for NG rehydration failure, namely the presence of intractable vomiting. Methods: A prospective case-control study was performed at the pediatric emergency department of the Grenoble Alpes University Hospital between 2014 and 2018. 477 children with mild-to-moderate dehydration due to viral AGE and requiring NG rehydration were included. Cases were defined as children with NG rehydration failure and therefore requirement for IV rehydration. Anamnestic and clinical data of cases and controls were compared. Results: The NG rehydration failure rate is 18%. 60% of children had intractable vomiting and 47% had intractable diarrhoea. Intractable vomiting were significantly more frequent in children with a NG rehydration failure: OR=2.92; [1.8-4.73], p=0.001 with more than a doubling of failure rate (22% versus 12%). Other observed risks factors were more than 5 vomiting episodes in the last 24 hours (p

Introduction : Under-nutrition and over-nutrition are major nutritional problems during and after oncological treatment. Body composition in an essential tool in nutrional status follow-upIt indeed allows for the detection of fat mass (FM) ans fat free mass (FFM) changes and is essential to adapt the nutrional support. The aim is this is to analyse the changes in body composition during the cancer treatment in children. The effect of the types of tumor and of treatment have been analysed.Methods : A prospective cohort study of 15 newly diagnosed cancer patients with maligancies. Anthropometric data (weight, height) and body composition was assessed at diagnosis and 1, 3, 6, 9 and 12 months after diagnosis. Results : A decrease of FFM and an increase of FM and a weight gain were found in patient with hematological malignancies during the first three months. A greater number of patients were diagnosed with overnutrition (FM>+2 standart deviations) with analysis of body composition as compared to BMI. Conclusion : The fat mass increased after the most intensive period of treatment with a decreased of the fat free mass.; Introduction : Dénutrition et surnutrition sont des problèmes nutritionnels majeurs pendant et après le traitement du cancer. Leur prise en charge implique un suivi précis de la composition corporelle (CC). Le but de cette étude était donc d’étudier l’évolution de la CC des enfants atteints de pathologies cancéreuses pendant leur traitement. L’incidence du type de tumeur et du traitement sur la CC a également été analysée, ainsi que la recherche de corrélations statistiques entre les différents composant de la CC et les marqueurs traditionnels de l’état nutritionnel. Méthodes : Il s’agit d’une étude prospective observationnelle de 15 patients nouvellement diagnostiqués d’une pathologie maligne. Des mesures anthropométriques (poids, taille) et de CC par impédancemétrie bioélectrique ont été réalisées au diagnostic, puis à 1, 3, 6, 9, 12 mois de suivi. Résultats : Une baisse de MM et une augmentation importante de MG étaient constatées au cours des trois premiers mois de traitement, associées à un gain de poids. Le suivi de la CC permettait de repérer un nombre plus important d’enfants surnutris (MG>+2 déviations standards (DS)) que le seul suivi du poids et de l’ IMC (Indice de Masse Corporelle). Conclusion : Le taux de MG augmente pendant la période intensive de traitement concomitante à la fonte de la MM.

Children receiving long-term enteral feeding may fail to develop oro-motor feeding skills. This lead to feeding disorders like food refusal and oral aversion to the point of feeding tube dependency, defined as more than 3 months of tube feeding without any medical condition that interferes with eating or swallowing. An Austrian team provides an intensive inpatient tube weaning program with a multidisciplinary team, known as the “Graz-model”. The main intervention is the promotion of hunger by reducing tube feeding dramatically in the first three days. Self-feeding is promoted: the child is continuously in contact with food. After 3 weeks of treatment, complete weaning rates is 80%, with a mean weight loss of 4.3%. This treatment doesn’t actually exist in France. We reviewed cases of 8 children from the Grenoble Alpes University Hospital, who followed the “Graz-model” after failure of the usually weaning method. We then discussed the benefits and the inconveniences of this model.; Les enfants ayant une nutrition entérale prolongée peuvent développer des troubles de l’oralité. Chez certains, ces troubles causent des difficultés alimentaires majeures et donc des difficultés de sevrage de la nutrition entérale alors qu’elle n’est plus justifiée par une pathologie médicale. On parle alors de dépendance à la nutrition entérale. Une équipe autrichienne, à Graz, propose un modèle de sevrage rapide, lors d’une hospitalisation de 2 à 3 semaines, fondée sur la provocation d’une faim intense en réduisant fortement et rapidement les apports entéraux et sur l’autonomie de l’enfant pour arriver à manger. Le taux de succès de cette méthode atteint 80% en fin d’hospitalisation, avec une perte de poids aiguë moyenne de 4,3%. Ce modèle n’est actuellement pas développé en France. Nous présentons les cas de 8 enfants du CHU Grenoble Alpes ayant suivi le modèle de sevrage de Graz après échec de la méthode habituelle de sevrage, puis une discussion des avantages et inconvénients de ce modèle.

Introduction : La dénutrition est fréquente et augmente la morbi-mortalité des enfants traités pour une pathologie maligne. Cependant, l'incidence et les facteurs de risque de la dénutrition et de la dénutrition prolongée (> 3 mois) ne sont pas clairement définis. Cette étude rétrospective avait pour objectif de décrire l'incidence et de préciser les facteurs de risque et complications de la perte de poids majeure (PdPM), de la dénutrition et de la dénutrition prolongée dans cette population. Matériels et méthodes : La dénutrition était définie par le score de Waterlow (poids pour taille < 90%). La PdPM était définie selon les critères de Martin et al. Les poids et tailles des enfants ont été relevés de façon mensuelle, pendant toute la durée du traitement. Résultats : 204 patients ont été inclus. Une PdPM est apparue dans 56% des cas et l'incidence cumulée de la dénutrition était de 45%. La dénutrition a duré plus de 3 mois chez 57 patients et plus de 6 mois chez 49 enfants. Les pathologies les plus à risque nutritionnel étaient les tumeurs osseuses, le médulloblastome, le rhabdomyosarcome, le neuroblastome, le néphroblastome et la leucémie aiguë lymphoïde. Les autres facteurs de risque retrouvés étaient la présence de métastases, la dénutrition et l’âge au diagnostic (< 3 ans ou ≥ 10 ans), la nécessité d'une intervention chirurgicale. Les principales complications de la PdPM et de la dénutrition étaient l'augmentation du nombre d'infections et de mucites, les retards thérapeutiques et la surmortalité. Conclusion : Cette étude souligne l'importance d'un support nutritionnel adapté. Un algorithme de prise en charge nutritionnelle est proposé.

In full-term newborns, transcutaneous estimation of serum bilirubin (SB) is reliable. However this method has not been validated in very preterm infants. Aim: Our objective was to investigate the accuracy of transcutaneous bilirubinometry (TcB) in preterm newborns with a gestational age (GA) < 30 weeks. Methods: This prospective multicenter study included 167 preterm neonates with a GA

Lipids are essential for the nutrition of premature neonates, as they provide energy and essential fatty acids. However their time of infusion is often delayed due to concerns regarding their tolerance. This study aims to assess the impact of early lipid infusion and their tolerance in premature neonates. Methods: We compared 132 neonates having received lipids before 24 hours of life (early lipid infusion, n=59) or during the third day (late lipid infusion, n=73). The nutritional intakes and the growth were registered during their hospital stay. Clinical and biological tolerance was studied, along with glycemic tolerance. Results: The 2 groups did not differ in gestational age, birth weight and gender. The lipid initial dose was between 0.5 and 1g/kg/d. The maximal weight loss was significantly lower in the early lipid infusion group (7.4 versus 9.3%, p=0,008), with less time required to regain birth weight in this group (8.0 versus 9.6, p=0.005), despite identical perfusion volumes. The weight at hospital discharge was greater in the early lipid infusion group (2707 vs 2521g, p=0.026). There were no criterions for poor clinical or biological tolerance. The glucose tolerance seemed better in the “early infusion group, with significantly less capillary glycaemia over 10mmo/l per patient (1.3 versus 3.6, p=0.025). The rates of complications associated with prematurity were identical in both groups. Discussion: Initial weight loss is often thought to be due to relative dehydration. Here we showed that early lipid intake reduces this initial weight loss, thus hinting that some part of malnutrition is involved. Conclusion: Early lipid infusion for the premature neonate allows a lower initial weight loss and a better growth until discharge. Furthermore it is well tolerated.; Du fait de leur apport énergétique et en acides gras essentiels, les lipides sont essentiels dans la nutrition du grand prématuré. Cependant, leur introduction était souvent retardée du fait d’inquiétudes par rapport à leur tolérance. Cette étude vise à montrer les bénéfices d’une introduction précoce des lipides sur la croissance du grand prématuré et à évaluer sa tolérance. Méthodes : Cent trente-deux enfants ≤ 32SA ont été inclus dans cette étude avant-après. Les lipides ont été introduits de façon précoce (avant 24 heures de vie, n=59) ou tardive (au troisième jour de vie, n=73). Les apports nutritionnels et la croissance pondérale ont été recueillis au cours du séjour. La tolérance était évaluée sur le plan clinique, biologique et sur la tolérance glycémique. Résultats : La perte de poids maximale était moindre dans le groupe des lipides précoces (7,4 versus 9,3%, p=0,008), ainsi que le délai de reprise du poids de naissance (8,0 versus 9,6, p=0,005). Le poids à la sortie était également plus important dans ce groupe (p=0.026). Il n’y avait pas de critères de mauvaise tolérance clinique ou biologique (cholestérolémie, triglycéridémie). Le nombre de glycémies capillaires > 10 mmol/l était significativement plus faible dans le groupe des lipides précoces (1,3 versus 3,6, p=0,025). Le taux de complications associés à la prématurité était identique dans les 2 groupes. Conclusion : L’apport précoce de lipides chez le grand prématuré permet donc une plus faible perte de poids initiale et une meilleure croissance. Cette introduction précoce est bien tolérée.