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Education and training may improve the prescription of pediatric parenteral nutrition. The aim was to evaluate the impact of an e-learning method on parenteral nutrition prescription skills among pediatric residents in 2 pediatric hospitals.A randomized double-blind control study was conducted over a 9-month period among pediatric residents in HOSP1, Geneva, Switzerland, where physicians prescribe parenteral nutrition directly, and in HOSP2, Montreal, Canada, where physicians prescribe only occasionally because clinical pharmacists are devoted to this activity. The intervention consisted of an e-learning session about key issues of parenteral nutrition. Physician parenteral nutrition knowledge was evaluated with a standardized questionnaire based on clinical cases before and after the e-learning in the intervention groups; in the control groups, only the 2 tests were conducted. In HOSP1, participants also underwent iterative tests every 2 months to measure the retention of knowledge.Sixty-five physicians participated. Initial knowledge scores were higher in HOSP1 (pretest scores 180 ± 29 vs 133 ± 24, p 0.001). Overall, there was no significant difference in the impact of the e-learning intervention between the control and e-learning groups (p 0.05). A significant knowledge improvement was observed in HOSP2 in the e-learning group (p = 0.033). Iterative tests in HOSP1 showed persistence of knowledge without significant differences between the groups. E-learning satisfaction among the participants was outstanding (100%).E-learning seems to be an effective method for teaching parenteral nutrition among pediatric residents and fellows at the beginning of the training. High satisfaction with this teaching method was observed in this study.

Despite growing interest about the impact of donor-specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single-center chart review of children (0-16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient- and donor-characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow-up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty-eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6-7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.

To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.

The nutritional composition of human milk evolves over the course of lactation, to match the changing needs of infants. This single-arm, non-inferiority study evaluated growth against the WHO standards in the first year of life, in infants consecutively fed four age-based formulas with compositions tailored to infants’ nutritional needs during the 1st, 2nd, 3rd–6th, and 7th–12th months of age. Healthy full-term formula-fed infants (n = 32) were enrolled at ≤14 days of age and exclusively fed study formulas from enrollment, to the age of four months. Powdered study formulas were provided in single-serving capsules that were reconstituted using a dedicated automated preparation system, to ensure precise, hygienic preparation. The primary outcome was the weight-for-age z-score (WAZ) at the age of four months (vs. non-inferiority margin of −0.5 SD). Mean (95% CI) z-scores for the WAZ (0.12 (−0.15, 0.39)), as well as for the length-for-age (0.05 (−0.19, 0.30)), weight-for-length (0.16 (−0.16, 0.48)), BMI-for-age (0.11 (−0.20, 0.43)), and head circumference-for-age (0.41 (0.16, 0.65)) at the age of four months, were non-inferior. Throughout the study, anthropometric z-scores tracked closely against the WHO standards (within ±1 SD). In sum, a four-stage, age-based infant formula system with nutritional compositions tailored to infants’ evolving needs, supports healthy growth consistent with WHO standards, for the first year of life.

Construct: This study aims to provide validity evidence for the standardized Assessment Letter for Pediatrics as a measure of competencies expected of a 1st-year pediatrics resident as part of a pediatric residency admissions process.The Narrative Letter of Recommendation is a frequently used tool in the residency admissions process even though it has poor interrater reliability, lacks pertinent content, and does not correlate with residency performance. A newer tool, the Standardized Letter, has shown validity evidence for content and interrater reliability in other specialties. We sought to develop and provide validity evidence for the standardized Assessment Letter for Pediatrics.All 2012 and 2013 applicants invited to interview at the University of Geneva Pediatrics Residency Program provided 2 standardized Assessment Letters. Content for the letter was based on CanMEDS roles and ratings of 6 desired competencies and an overall assessment. Validity evidence was gathered for internal structure (Cronbach's alpha and generalizability), response process (interrater reliability with intraclass correlation), relations to other variables (Pearson's correlation coefficient), and consequences (logistic regression to predict admission).One hundred fourteen faculty completed 142 standardized Assessment Letters for 71 applicants. Average overall assessment was 3.0 of 4 (SD = 0.59). Cronbach's alpha was 0.93. The G-coefficient was 0.59. The decision study projected that four Assessment Letters are needed to attain a G-coefficient of 0.73. Applicant variance (28.5%) indicated high applicant differentiation. The Assessment Letter intraclass coefficient was 0.51, 95% confidence interval (CI) [0.43, 0.59]. Assessment Letter scores were correlated with the structured interview (r = .28), 95% CI [0.05, 0.51]; global rating (r = .36), 95% CI [0.13, 0.58]; and admissions decision (r = .25), 95% CI [0.02, 0.46]. Assessment Letter scores did not predict the admissions decision (odds ratio = 1.67, p = .37) after controlling for the unique contribution of the structured interview and global rating scores.Validity evidence supports use of the Assessment Letter for Pediatrics; future studies should refine items to improve predictive validity and explore how to best integrate the Assessment Letter into the residency admissions process.

BACKGROUND The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. METHODS One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. RESULTS Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. CONCLUSIONS Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990-12/2011, medium follow-up 7.9 yr). One-, five-, and 10-yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26-fold) and early HAT (48 yr (increase 1.09-fold) and MELD score >30 (increase 1.2-fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary-enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.

Die Lebertransplantation bei Kindern ist ein ausserst komplexer medizinisch-chir­urgischer Eingriff, der an Personal und Medizintechnik extrem hohe Anspruche stellt. Bei terminalen Lebererkrankungen von Kindern ist sie heute die Behandlung der Wahl. Dank ihr konnen junge Patienten, deren Leben bedroht ist, eines ­Tages aktive Burger und Eltern werden. Indem wir fur ihre Gesundheit sorgen, ­investieren wir zugleich in unsere Gesellschaft!

La transplantation hepatique chez l’enfant est un traitement medico-chirurgical hautement complexe et extremement demandeur en ressources humaines et ­medico-techniques. Elle constitue aujourd’hui le traitement de choix des maladies terminales du foie de l’enfant. Elle permet a des jeunes patients dont le pronostic vital est menace de devenir un jour des citoyens actifs, des parents. Miser sur leur sante est donc un investissement pour notre societe!

The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl

As children referred for OLT in Switzerland were not vaccinated optimally, new guidelines were developed and recommended to base catch-up immunization on serum antibody titers against vaccine-preventable diseases, before and after OLT. We measure the results of this serology-based intervention by comparing vaccine coverage and antibody titers in the pre- (1990-2002, P1) and post-intervention (2003-2008, P2) cohorts in a quality control project. Forty-four P1 and 30 P2 children were evaluated. At pre-OLT visit, D, T, SPn, and MMR serologies were checked more frequently in P2 than P1 (p

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver-kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.

Chronic granulomatous disease (CGD) is an immunodeficiency caused by the lack of the superoxide-producing phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, CGD patients not only suffer from recurrent infections, but also present with inflammatory, non-infectious conditions. Among the latter, granulomas figure prominently, which gave the name to the disease, and colitis, which is frequent and leads to a substantial morbidity. In this paper, we systematically review the inflammatory lesions in different organs of CGD patients and compare them to observations in CGD mouse models. In addition to the more classical inflammatory lesions, CGD patients and their relatives have increased frequency of autoimmune diseases, and CGD mice are arthritis-prone. Possible mechanisms involved in CGD hyperinflammation include decreased degradation of phagocytosed material, redox-dependent termination of proinflammatory mediators and/or signaling, as well as redox-dependent cross-talk between phagocytes and lymphocytes (e.g. defective tryptophan catabolism). As a conclusion from this review, we propose the existence of ROS high and ROS low inflammatory responses, which are triggered as a function of the level of reactive oxygen species and have specific characteristics in terms of physiology and pathophysiology.

OBJECTIVES Obesity has been associated with increased bone mass, but the mechanisms involved are still poorly understood. We aimed to explore the relation between bone mineral density and factors known to influence bone formation in obese and lean adolescents. METHODS We recruited 24 obese and 25 lean adolescents in a case-control study. Total body bone mineral density (TB-BMD) z scores and body composition were determined using dual-energy x-ray absorptiometry. We measured 25-hydroxyvitamin D (25-OH-D), glucose, insulin, and leptin concentrations. Physical activity (PA) level was quantified using accelerometer. RESULTS TB-BMD z score was higher, whereas 25-OH-D and PA levels were lower in obese compared with lean subjects (TB-BMD z score 1.06 ± 0.96 vs 0.26 ± 0.91, P = 0.004; 25-OH-D 9.9 ± 6.4 vs 18.5 ± 7.4 ng mL, P

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

Background: Loss of triphasicity of hepatic venous flow on Doppler US has been correlated with hepatic parenchymal disease such as cirrhosis and graft rejection in adults. Objective: To document physiological variations of hepatic vein (HV) flow patterns in normal children of different age groups, the influence of age, sex, body position, site of measurements within a given vein, exercise and food intake. Also, to document the reproducibility of the Doppler US findings in the three major HVs, in order to establish the limits of normal flow against which to assess liver pathology giving rise to abnormal flow pattern. Materials and methods: Thirty-two children, divided into four age groups: less than 1 year, 1–5 years, 5–12 years and 12–16 years, with four boys and four girls in each group, underwent repeated US examinations of their HVs. The HV flow pattern was recorded as triphasic = 4, diphasic = 3, monophasic = 2 or uninterpretable = 1 at three sites in each vein: peripheral, middle and proximal in the supine position in the fasting state. One recording was then obtained in the midportion of each vein in the sitting position, another one after exercise, then after a meal and lastly one by a second radiologist. Statistical analysis of variance was done of each variable alone, in combination two by two and three by three. Results: HV flow pattern was different from one vein to another in the majority of the children, the right HV having the least triphasic flow. Age was highly significant, the HV flow being less triphasic in young children. Sex and position were significant for the right HV only, which was the most difficult to examine. Exercise and food intake did not change the triphasicity of flow. Conclusions: HV flow pattern differs with age and can differ from one HV to another within an apparently normal liver. Interpretation is generally reproducible from one radiologist to another. A difference of sex, seen mostly for the right HV, may be due to unfavourable Doppler angle and difficulty of interpretation. The site of measurements within a given vein, body position, exercise and food intake do not influence the triphasicity of HV flow.

This study intends to document the presence or absence of triphasic waveforms in hepatic veins in healthy children. Does absence of triphasic hepatic vein flow indicate hepatic abnormality?One hundred children without a known hepatic or intrathoracic abnormality underwent Doppler sonography of their hepatic veins. Fifty girls and 50 boys were divided into five age groups.Forty-two children had triphasic flow in all three hepatic veins. Veins approaching an angle of 90 degrees with the inferior vena cava could not be assessed or had the least flow modulations despite angle correction. Neonates had the highest percentage of monophasic flow (seven of 21) in all three hepatic veins and none had triphasic flow in all three veins.Not all healthy children have a triphasic flow pattern in all hepatic veins. Before suspecting hepatic abnormality with abnormal parenchymal compliance (cirrhosis, graft rejection) by virtue of lack of triphasic hepatic vein flow, a normal variant of the flow should be considered. Only the change of a previously documented triphasic flow to monophasic flow in a given vein should be assessed as a sign of possible abnormality.

To determine the incidence and etiology of chylothorax and to assess our therapeutic management approach.We reviewed 51 patients diagnosed with chylothorax over a 12-year period. Cause, interval between operation and diagnosis, duration of chylothorax, and total volume loss per weight were recorded.Chylothorax was diagnosed in 46 children after cardiothoracic surgery, giving an incidence of 2.5% (46/1842); in 1 child chylothorax occurred after chest trauma, and in 4 the chylothorax was congenital or a manifestation of lymph angiomatosis. Three etiologic groups were identified: group 1, direct injury to the thoracic duct (33/51 = 65%); group 2, thrombosis and/or high venous pressure in the superior vena cava (14/51 = 27%); and group 3, congenital (4/51 = 8%). Conservative treatment was the only treatment in 80% of the patients. Surgical procedures consisted of 4 ligations of the thoracic duct, placement of 7 pleurodesis shunts, and placement of 2 pleuroperitoneal shunts. Patients in groups 2 and 3 were at higher risk for failure of conservative treatment (P. 005). Longer duration of chylothorax and higher volume of drainage were present in group 2 compared with group 1 (P.01).Conservative treatment was successful in 80% of the patients with our management approach. Prevention, early recognition, and treatment of potential complications, such as superior vena cava thrombosis or obstruction, may further improve success of conservative treatment. Congenital chylothorax seems different and may require a specific approach.

The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.

Background: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. Methods: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. Results: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. Conclusions: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Psychomotor development in pediatric liver transplant (LT) recipients depends on several factors. Our aim was to evaluate the importance of parental involvement and family dynamics on psychomotor development by assessing (i) children and parents individually, (ii) the parent-child relationship, and (iii) the correlation between parental functioning and patient outcome, all before and after LT. Age-appropriate scales were used before and after LT. Twenty-one patients, 19 mothers, and 16 fathers were evaluated. Developmental quotient (DQ): No subjects scored in the "very good" range. The proportion of children with deficits increased from LT to two yr: 17.6% vs. 28.6%. Subjects 0-2 yr were more likely to have normal DQ at transplant (66.7% vs. 50% for older children). Abnormal DQ was more prevalent two yr post-LT in children older at LT (p = 0.02). The mother-child relationship was normal in 59% of families pre-LT and in 67% at two yr. The relationship was more favorable when the child received a transplant as an infant (p = 0.014 at 12 months post-LT). Normal DQ was associated with higher maternal global functioning score pre-LT (p = 0.03). Paternal performance scores were higher than maternal scores. Children transplanted after two yr of age suffer greater long-term deficits than those transplanted as infants.

Discordant results have been reported about the role of lymphocyte proliferation assays in patients with cow's milk allergy. We studied the peripheral blood mononuclear cell response of 10 children with cow's milk allergy by means of a lymphocyte proliferation test to determine the diagnostic value of this assay, the clinical tolerance of a new therapeutic hydrolyzed formula, and the evolution of lymphocyte proliferation after 3 months of a cow's milk-free diet with the hydrolyzed formula. The lymphocyte proliferation at the time of diagnosis in the patients with cow's milk allergy was not statistically different from the results in the control group. The proliferation test performed after 3 months of diet with the hydrolyzed formula and restriction of cow's milk protein showed that the cellular proliferation remained globally the same compared with the proliferation at the time of diagnosis. The hydrolyzed formula proteins induced a lower cellular proliferation than milk proteins in patients with cow's milk allergy. Our results suggest that the lymphocyte proliferation test cannot be recommended for diagnostic purposes. However, in patients with cow's milk allergy the proliferation test affirmed the absence of immunogenicity of the hydrolyzed formula because it induced no significant T-cell activation.

Varicella can have a severe course in immunosuppressed patients. Although prevention is fundamental, live-attenuated varicella-zoster (VZV) vaccine is not currently recommended in transplant recipients. Our aims were to (1) evaluate VZV immunity in pediatric liver transplant (LT) recipients; (2) immunize (two doses) seronegative patients post-LT; (3) monitor vaccine safety, (4) assess B and T cell vaccine responses. All patients followed at the Swiss National Pediatric LT Center were approached and 77/79 (97.5%) were enrolled (median age 7.8 years). Vaccine safety was monitored by standardized diary cards and phone calls. VZV-specific serology and CD4(+) T cells were assessed before and after immunization. Thirty-nine patients (51.1%) were seronegative including 14 children immunized pre-LT. Thirty-six of 39 seronegative patients were immunized post-LT (median 3.0 years post LT). Local (54.8%) and systemic (64.5%) reactions were mild and transient. The frequency of VZV-specific CD4(+) T cells and antibody titers increased significantly (respectively from 0.085% to 0.16%, p = 0.04 and 21.0 to 1134.5 IU/L, p < 0.001). All children reached seroprotective titers and 31/32 (97%) patients assessed remained seroprotected at follow-up (median 1.7 years). No breakthrough disease was reported during follow-up (median 4.1 years). Thereby, VZV vaccine appears to be safe, immunogenic and provide protection against disease in pediatric LT patients.

Objectives: Little is known about pancreatic fat accumulation and its possible associations with metabolic syndrome (MetS) and glucose metabolism. The aim of the present study was to quantify pancreatic fat fraction (PFF) in lean and obese adolescents and explore its relation to metabolic parameters. Methods: We recruited 25 lean and 24 obese adolescents. PFF and visceral adipose tissue (VAT) were determined using magnetic resonance imaging. We measured blood pressure, fasting glucose, insulin, liver enzymes, leptin, and lipid levels. Obese subjects underwent an oral glucose tolerance test. Results: PFF was significantly higher in obese than in lean subjects (4.8 � 1.2 vs 3.6 � 0.9; P < 0.001) and was associated with VAT, g-glutamyltransferase, triglycerides, high-density lipoprotein cholesterol, leptin concentrations, and MetS (P < 0.05 for all). None of the obese subjects had glucose intolerance, but when adjusted for VAT, the following 3 parameters correlated negatively with PFF: fasting and 30minute and 120-minute insulin levels. We divided subjects into 3 groups: group I, lean without MetS; group II, obese without MetS; and group III, obese with MetS, and observed that PFF increased gradually among groups (I: 3.56% � 0.88%; II: 4.70% � 1.06%; III: 5.34% � 1.49%; P < 0.001). Conclusions: Obese adolescents accumulate fat in the pancreas. PFF correlates with the presence of MetS. Even in the absence of glucose intolerance, pancreatic fat deposition is associated with impaired insulin response to glucose overload. This suggests that b-cell dysfunction may already be present in nondiabetic obese adolescents, mirroring what has been shown in adults, and that pancreatic fat accumulation may participate in obesity-associated pancreatic endocrine dysfunction.

Clinical trials have demonstrated that the risk of developing atopic dermatitis is reduced when using hydrolysed formulas to feed infants with a documented risk of atopy (i.e. an affected parent and/or sibling)when breastfeeding is not practised. However, little is known about the cost-effectiveness of using hydrolysed formulas. Consequently, economic analyses in 5 European countries (Denmark, France, Germany, Spain and Switzerland) have evaluated the costs and cost-effectiveness of a specific brand of 100% whey-based partially hydrolysed infant formula, NAN-HA® (PHF-W) compared with a cow’s milk standard formula (SF) in the prevention of atopic dermatitis in at-risk children. This review synthesises the findings of these studies. Cost-effectiveness analyses (CEA) used a decision-analytic model to determine treatment pathways, resource utilisation and costs associated with the management of atopic dermatitis in healthy at-risk newborns who were not exclusively breastfed. The model had a 12-month horizon and applied reimbursement rates of 60–100% depending on the country. Outcomes were considered from the perspective of the public healthcare system (e.g. the Ministry of Health; MOH), family and society. The final outcome was the incremental cost-effectiveness ratio per avoided case of atopic dermatitis (ICER) for PHF-W versus SF. A cost-minimisation analysis was also performed to compare PHF-W with extensively hydrolysed formulas (EHF). The base-case CEA produced ICERs per avoided case for PHF-W versus SF of EUR 982–1,343 (MOH perspective), EUR –2,202 to –624 (family perspective) indicating savings, and EUR –1,220 to 719 from the societal perspective. The main costs related to formula (MOH and society) and time loss (family). In the cost-minimisation analysis, PHF-W yielded savings of between EUR 4.3 and 120 million compared with EHF-whey when the latter was used in prevention. In conclusion, PHF-W was cost-effective versus SF in the prevention of atopic dermatitis and cost saving compared with EHF when used in prevention.

A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a partially hydrolyzed 100% whey-based infant formula, NAN-HA®, manufactured by Nestlé S.A, Switzerland (PHF-W), branded under BEBA HA® in Switzerland, in the prevention of atopic dermatitis (AD) in 'at risk' Swiss children when compared to standard cow's milk formula (SF).Based on a 12-month time horizon including 6 months of formula consumption, an economic model was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in healthy 'at risk' Swiss newborns who could not be exclusively breastfed. Model inputs were retrieved from the literature, official formularies, and expert opinion. The treatment pathways considered a medical treatment approach, supplemented in some instances by a change of formula. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost effectiveness ratio (ICER) for PHF-W vs SF. Outcomes were presented from three perspectives: the Swiss public healthcare system (MOH), the subject's family, and society (SOC). A secondary analysis compared PHF-W to whey-based extensively hydrolyzed formula (EHF) in prevention.The model yielded 1653 avoided AD cases by selecting PHF-W over SF in a birth cohort of 22,933 'at risk' infants. The base case analyses generated an expected ICER of CHF 982 from the MOH perspective as well as savings of CHF 2202 and CHF 1220 from the family and SOC perspectives, respectively. PHF-W yielded CHF 11.4M savings against EHF when the latter was assumed to be used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model.Under a range of assumptions, this analysis has established the dominance from the family and societal perspectives and cost-effectiveness from the MOH perspective of PHF-W vs SF in the prevention of AD among 'at risk' Swiss infants.

The objective of the study was to evaluate gastric myoelectrical activity in young patients with diabetes and to correlate it with their metabolic control [fasting blood glucose, glycosylated haemoglobin, and fructosamine] and BMI during a 3 years follow-up.Surface electrogastrography (EGG) was performed on 49 children with diabetes aged 10.3±4.4 (mean±SD) years and 17 age-matched healthy controls after fasting glucose, glycosylated haemoglobin, and fructosamine were measured. EGG parameters [percentage of bradygastria, 3 cycles per minute, tachygastria, dominant frequency instability coefficient, and power ratio] were analysed and compared with blood analysis.Patients with diabetes exhibited an increase in preprandial bradygastria 7.9±8.8 cpm (mean±SD) compared with controls 2.1±1.0 (P=0.011), with an associated decrease in preprandial normogastria (72.2±14.5 vs. 82.7±14.7; P=0.013). Normogastric power ratio (postprandial/ preprandial power) was significantly increased in the children with diabetes compared with controls (mean: 6.67 vs. 3.14, P=0.034). A longer duration of diabetes was associated with an increased risk of EGG abnormalities (P=0.036). Marked hyperglycaemia at the time of study was associated with postprandial bradygastria (P=0.01) and power ratio bradygastria (P=0.042). Changes in glycosylated haemoglobin, fructosamine and BMI did not affect EGG parameters.EGG abnormalities, presented early in a high proportion of diabetic children, are related to the acute hyperglycaemia. These abnormalities are not consistently present in the follow-up studies and not related to the glycosylated haemoglobin and fructosamine. Diabetic autonomic neuropathy is therefore an unlikely pathogenic factor for EGG abnormalities in children with diabetes.

Background DNA polymerase γ (POLG) is the only known mitochondrial DNA (mtDNA) polymerase. It mediates mtDNA replication and base excision repair. Mutations in the POLG gene lead to reduction of functional mtDNA (mtDNA depletion and/or deletions) and are therefore predicted to result in defective oxidative phosphorylation (OXPHOS). Many mutations map to the polymerase and exonuclease domains of the enzyme and produce a broad clinical spectrum. The most frequent mutation p.A467T is localised in the linker region between these domains. In compound heterozygote patients the p.A467T mutation has been described to be associated amongst others with fatal childhood encephalopathy. These patients have a poorer survival rate compared to homozygotes. Methods mtDNA content in various tissues (fibroblasts, muscle and liver) was quantified using quantitative PCR (qPCR). OXPHOS activities in the same tissues were assessed using spectrophotometric methods and catalytic stain of BN-PAGE. Results We characterise a novel splice site mutation in POLG found in trans with the p.A467T mutation in a 3.5 years old boy with valproic acid induced acute liver failure (Alpers-Huttenlocher syndrome). These mutations result in a tissue specific depletion of the mtDNA which correlates with the OXPHOS-activities. Conclusions mtDNA depletion can be expressed in a high tissue-specific manner and confirms the need to analyse primary tissue. Furthermore, POLG analysis optimises clinical management in the early stages of disease and reinforces the need for its evaluation before starting valproic acid treatment.

In this paper, a Working Group on Gastro-Oesophageal Reflux discusses recommendations for the first line diagnostic and therapeutic approach of gastro-oesophageal reflux disease in infants and children. All members of the Working Group agreed that infants with uncomplicated gastro-oesophageal reflux can be safely treated before performing (expensive and often unnecessary) complementary investigations. However, the latter are mandatory if symptoms persist despite appropriate treatment. Oesophageal pH monitoring of long duration (18-24 h) is recommended as the investigation technique of choice in infants and children with atypical presentations of gastro-oesophageal reflux. Upper gastro-intestinal endoscopy in a specialised centre is the technique of choice in infants and children presenting with symptoms suggestive of peptic oesophagitis. Prokinetics, still a relatively new drug family, have already obtained a definitive place in the treatment of gastro-oesophageal reflux disease in infants and children, especially if "non-drug" treatment (positional therapy, dietary recommendations, etc.) was unsuccessful. It was the aim of the Working Group to help the paediatrician with this consensus statement and guide-lines to establish a standardised management of gastro-oesophageal reflux disease in infants and children.

Cholestasis is one of the most frequent complications of Total Parenteral Nutrition (TPN). Among the components of TPN, amino acids (AA) and dextrose are considered responsible in terms of quantity. The aim of this study was to determine whether IV lipids have a protective effect on the liver lesions induced by TPN, as well as on the bile flow in rats. Two groups of 6 animals, 6 receiving TPN containing AA and dextrose (Group A-D) and 6 receiving AA, dextrose and lipids (Group A-D-L) were studied. Both groups received the same amount of AA (3.4 g/day) and the same amount of energy (50 kcal/day). The TPN lasted 3 days, after which blood samples were obtained for liver function tests and the bile flow was determined gravimetrically, subsequently the liver was removed for histological analysis. A significant weight loss (p0.01) was observed in both groups (Group A-D: -13 +/- 4 g; Group A-D-L: -16 +/- 2g). The bile flow was significantly lowered in A-D-L at 10.14 +/- 1.27 microliters/minute when compared to Group A-D (15.61 +/- 1.31 microliters/minute). The Aspartate Amino Transferase (AST) plasma level was elevated at 188 +/- 20 UI in Group A-D and at 185 +/- 33 UI in Group A-D-L. Gamma-Glutamyl-Transferase (gamma-GT) plasma level was in the normal range in both groups. In conclusion, this study indicates that TPN-associated cholestasis is significantly increased by lipid addition. However, the hepatocellular necrosis seems unchanged.

The IRIS was initially described in HIV-positive patients as a sudden clinical deterioration after the introduction of highly active retroviral therapy. It is believed that IRIS is caused by a restored and exaggerated inflammatory immune response to different infectious or non-infectious triggers. This abnormal response is the consequence of an imbalance between pro-inflammatory and anti-inflammatory states. Recently, IRIS has also been reported in adult SOT recipients, causing local and systemic manifestations, and compromising long-term graft function and patient survival. However, IRIS has to date not been reported in pediatric SOT recipients. Here we review what is known and speculated about the pathogenesis of IRIS and propose that children may be relatively protected from IRIS.

A 6-month-old boy presents with a temperature of 38.9°C and barking cough of 3 days’ duration as well as a rash over his body for 1 day. On physical examination, his temperature is 37.5°C, respiratory rate is 28 breaths/min, and blood pressure is 87/52 mm Hg. He appears nontoxic and has a barking cough, injected conjunctiva with whitish discharge, dry lips, mild inspiratory stridor, a blanching erythematous maculopapular rash on his trunk and extremities, and small cervical lymph nodes. The rest of his physical findings are normal. His Hgb is 12.8 g/dL (128 g/L), WBC count is 11.7×103/mcL (11.7×109/L) with 75% neutrophils and 23% lymphocytes, and platelet count is 515×103/mcL (515×109/L). His stridor is considered to be due to viral croup, and he is treated with intramuscular (IM) dexamethasone and nebulized racemic epinephrine. A lateral neck radiograph reveals widening of the retropharyngeal space (Fig. 1), and he is started on clindamycin. CT scan of the neck reveals a right retropharyngeal abscess (Fig. 2). He continues to have high spiking fevers and experiences stridor at rest. He is started on IM dexamethasone every 6 hours, and his fever subsides the following day. Figure 1. Lateral neck radiograph showing widening of the retropharyngeal space. Figure 2. CT scan of the neck showing a right retropharyngeal abscess (arrow). On hospital day 6, the corticosteroids are stopped, but the fever returns the following day. Two days later, an erythematous maculopapular rash reappears, and the child’s lips are dry and cracked. On day 10, repeat CT scan shows that the retropharyngeal abscess has resolved. An additional imaging study reveals the cause of his symptoms. A 3-month-old previously healthy girl presents to the ED with a 1-day history of a blistering rash. Her parents noted an erythematous area on her occiput after …

Food allergies have increased over the past decade and are an important problem in daily clinical practice. They affect 6% of children and 3 to 4% of adults. Furthermore, around 20% of the population falsely believe that they are allergic to some foods and follow unnecessarily restrictive diets. For infants, the problem is even more acute as they need appropriate feeding in order to achieve normal growth and avoid bone and metabolic problems. Although any food can cause a reaction, few foods are responsible for the large majority of the symptoms: i.e., milk, eggs, wheat, peanuts, nuts, fish, shellfish. Of these, cow's milk allergy is frequently suspected in small children. It can be responsible of a variety of symptoms and can be caused by IgE-mediated or non-IgE-mediated reactions. The diagnosis relies on a detailed history, skin tests, laboratory tests, an elimination diet and food challenges. The overall natural evolution of the disease is favourable with most patients achieving tolerance to milk by the age of five years, but some patients will remain allergic for life.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P

Twenty-four children with postoperative chylothorax were encountered among 1,264 consecutive thoracic operations over a 7-year period and form the basis of this study. Chylothorax was caused by direct lesion to the thoracic duct or lymphatic vessels in 17 patients and was associated with superior vena cava (SVC) obstruction in seven. Of the latter, five had bilateral chylothorax. Chylothoraces secondary to venous hypertension and thrombosis have a longer interval between operation and diagnosis compared with direct trauma as well as a longer duration and larger volume of chylous drainage. Treatment was entirely nonoperative in 16 patients and operative in 8. Nonoperative treatment consisted of pleural needle aspiration or suction drainage in association with a medium chain triglyceride (MCT) diet (n = 11) or total parenteral nutrition (TPN) after failure of MCT (n = 5). Direct operation on the thoracic duct was performed in 5 patients, four had pleurodesis, and 2 had pleuroperitoneal shunts inserted. All patients were cured of their chylothorax and there were no deaths. Patients with major vein thrombosis were the most difficult to treat. On the basis of this experience, we suggest a step-by-step approach: (1) insertion of chest tube after 3 to 4 pleural punctures; (2) 1-week trial of MCT diet, with intravenous support to correct protein losses; (3) TPN if chylothorax increases or persists with large volumes; (4) Doppler echocardiography or phlebography to rule out obstruction of major thoracic veins; and (5) insertion of TPN line in inferior vena cava in case of such obstruction; and (6) direct surgical approach to the thoracic duct after 4 weeks of unsuccessful nonoperative treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a 9-year-old girl with cereulide-producing Bacillus cereus food poisoning, who developed fulminant hepatitis, renal and pancreatic insufficiency, shock, and prolonged seizures. She was transferred to our institution for hepatic transplantation before her diagnosis was established. As a result of rapid identification of the microorganism and supportive care, liver transplantation was avoided, and she recovered fully.

This report correlates the clinical and biological findings, liver hemodynamics and histological features of focal INL in an infant with BA cirrhosis. An eight month old boy with BA, with previous successful porto-enterostomy, was admitted with signs of cholangitis and ascites. He was treated with antibiotics and diuretics with subsequent clinical improvement. Eight days later, while being fed with hyper-osmolar milk, he became febrile again: ASAT/ALAT climbed (9000/2300 IU/L), liver function deteriorated. Infectious work-up was negative. Liver-ultrasound showed reversed portal flow and a negative arterial diastolic flow. The patient recovered within five days under supportive treatment. A similar event recurred five days later. INL was suspected and semi-urgent living-related liver transplantation was performed, with uneventful post-operative course. Histology of the explanted liver showed extensive foci of INL of different ages. This report illustrates how the association of reversed portal and arterial diastolic flows, with subsequent liver hypoperfusion, may repeatedly cause foci of INL in BA cirrhosis, and lead to rapid progression to liver failure. Because of precarious hepatic blood supply in such patients, close monitoring of portal and diastolic arterial flows is recommended.