High-flow nasal cannula vs standard respiratory care in pediatric procedural sedation: A randomized controlled pilot trial.

INTRODUCTION: Respiratory instability is frequently observed during pediatric procedural sedation. The aim of this trial was to estimate the impact of high-flow nasal cannula (HFNC) therapy on respiratory stability during sedation for upper gastrointestinal tract endoscopy in children. METHODS: Prospective randomized controlled non-blinded single-center pilot trial. Children were randomly allocated to receive either HFNC (2 L/kg/min) or low-flow nasal oxygen cannula (LFNC, standard care). FiO2 was titrated to maintain SpO2 94% to 98% in both groups. Primary outcome was the number of events of respiratory instability defined by prespecified criteria (hypoxia, hypercapnia, apnea). Secondary outcomes included type and duration of events, number of interventions to regain respiratory stability and cumulative doses of medication. RESULTS: Fifty children (mean age, 12.3 ± 3.1 years) were enrolled and treated with HFNC (n = 25) or LFNC (n = 25). Patient and intervention characteristics were not different in the two study groups, including total oxygen flow rate. Mean (SD) number of respiratory events in the HFNC group was 2.0 ± 1.9 events compared to 2.0 ± 1.4 events in the LFNC group (P = .65; 95% CI of difference, -1.0 to 1.0). There was no difference for any secondary outcome criteria, percentage of patients for any outcome criteria and no difference in the number of respiratory events or airway management maneuvers per patient between treatment groups. CONCLUSIONS: HFNC did not increase respiratory stability in sedated children undergoing upper gastrointestinal tract endoscopy compared to LFNC.

High blood pressure, a red flag for the neonatal manifestation of urea cycle disorders.

BACKGROUND: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH4+) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome. METHODS: Detailed information of 17 patients (born between 1994 and 2012) with confirmed diagnosis of UCD and neonatal hyperammonemic encephalopathy were collected from the original medical records. RESULTS: The initially suspected diagnosis was neonatal sepsis in all patients, but was not confirmed in any of them. Unlike neonatal sepsis and not previously reported blood pressure increased above the 95th percentile in 13 (81%) of UCD patients before emergency treatment was started. Respiratory alkalosis was found in 11 (65%) of UCD patients, and in 14 (81%) plasma NH4+concentrations further increased despite initiation of metabolic therapy. CONCLUSION: Detection of high blood pressure could be a valuable parameter for distinguishing neonatal sepsis from neonatal manifestation of UCD. Since high blood pressure is not typical for neonatal sepsis, other reasons such as encephalopathy and especially hyperammonemic encephalopathy (caused by e.g. UCD) should be searched for immediately. However, our result that the majority of newborns with UCD initially present with high blood pressure has to be evaluated in larger patient cohorts.

Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment.

OBJECTIVE: Urinary copper excretion rates and non-caeruloplasmin associated copper concentrations are increased in patients with Wilson disease. However, there is little literature describing the monitoring of these parameters over the long term. METHODS: This is a monocentric retrospective study including data collected between 2003 and 2015 from 321 patients with Wilson disease by chart review. The patients were under therapy with D-penicillamine, trientine, or zinc. 24-h urinary copper excretion rates, non-caeruloplasmin associated copper, and total serum copper concentrations were determined at the start of therapy, as well as 6, 12, 18, 24, 36, and ≥ 60 months after the start of therapy. For patients taking chelating agents, all parameters were measured while under continued therapy, as well as after a 48-h dose interruption. A mathematical formula to predict 24-h urinary copper excretion rates under different therapies was established. RESULTS: In all treatment groups, urinary copper excretion rates decreased over time, but the inter-individual variation of the results was high. Non-caeruloplasmin associated copper concentrations tended to decline over time, but with a higher variation of results than that observed for urinary copper excretion rates. CONCLUSION: Due to their variability, urinary copper excretion rates and serum copper concentrations are less than ideal parameters by which to monitor the benefit of a copper-reducing therapy. Urinary copper excretion rates seem to be more suitable than non-caeruloplasmin associated copper concentrations for this purpose.

Limitations and opportunities of non-invasive liver stiffness measurement in children.

Changes in liver structure are an important issue in chronic hepatopathies. Until the end of the 20th century, these changes could only be determined by histological analyses of a liver specimen obtained via biopsy. The well-known limitations of this technique (i.e., pain, bleeding and the need for sedation) have precluded its routine use in follow-up of patients with liver diseases. However, the introduction of non-invasive technologies, such as ultrasound and magnetic resonance imaging, for measurement of liver stiffness as an indirect marker of fibroses has changed this situation. Today, several non-invasive tools are available to physicians to estimate the degree of liver fibrosis by analysing liver stiffness. This review describes the currently available tools for liver stiffness determination that are applicable to follow-up of liver fibrosis/cirrhosis with established clinical use in children, and discusses their features in comparison to the "historical" tools.

An Assessment of Publication Status of Pediatric Liver Transplantation Studies.

INTRODUCTION: Pediatric liver transplantation is a highly specialized, challenging field. Selective reporting may introduce bias into evidence based clinical decision making, but the precise extent of unpublished data in pediatric liver transplantation is unknown today. We therefore assessed the public availability of completed clinical trials in pediatric liver transplantation. METHODS: We determined the proportion of published and unpublished pre-registered, completed pediatric liver transplantation studies on ClinicalTrials.gov. The major trial and literature databases, i.e., clinicaltrials.gov, Pubmed, and Google Scholar were searched for publications. In addition, principal investigators or sponsors were contacted directly. STROBE criteria were applied for the descriptive analysis. RESULTS: Out of N = 33 studies focusing on pediatric liver transplantation registered as completed until March 2014 on clinicaltrials.gov, N = 19 (58%) studies were published until February 2015, whereas N = 14 (42%) studies remained unpublished. The unpublished trials contain data from N = 2105 (35%) patients out of a total population of N = 6044 study participants. Median time-to-publication, i.e., the period from completion of the trial until public availability of the data was 23 IQR 10 to 28 months. Most pertinent key questions in pediatric liver transplantation, i.e., surgical procedures, immunosuppression, concomitant infections, and graft rejection were addressed in 48% of studies (N = 16/33), half of which were published. CONCLUSION: Half of the clinical trials in pediatric liver transplantation focused on key questions such as surgical procedures, immunosuppression, concomitant infections, and graft rejection. There is still a considerable amount of unpublished studies results in pediatric liver transplantation. Time from study completion to publication was almost twice as long as the 12 months mandatory FDAAA-timeline with a trend towards acceleration over time. The data should serve as a baseline for future progress in the field. More stringent publication of completed trials and focused multicenter research should be encouraged.

High affinity anti-BSEP antibodies after liver transplantation for PFIC-2 - Successful treatment with immunoadsorption and B-cell depletion.

PFIC due to BSEP mutations (PFIC type 2) often necessitates OLT. It has recently been recognized that some PFIC-2 patients develop phenotypic disease recurrence post-OLT due to the appearance of anti-BSEP antibodies. Here, we describe a boy who became cholestatic four yr after OLT during modification of immunosuppression. Canalicular antibody deposits were detected in biopsies of the transplant and antibodies specifically reacting with BSEP were identified at high titers in his serum. These antibodies bound extracellular epitopes of BSEP and inhibited BS transport and were assumed to cause disease recurrence. Consequently, anti-BSEP antibody depletion was pursued by IA and B-cell depletion by anti-CD20 antibodies (rituximab) along with a switch of immunosuppression. This treatment resulted in prolonged relief of symptoms. Depletion of pathogenic anti-BSEP antibodies causing AIBD after OLT in PFIC-2 patients should be considered as a central therapeutic goal.

Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts Adverse Outcome in Pediatric Acute Kidney Injury.

BACKGROUND: The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet. METHODS: The product of the urinary concentration of TIMP-2 and IGFBP7 ([TIMP-2]•[IGFBP7]) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0-18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1). RESULTS: When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category "Risk", 13/46 (28%) for "Injury", 26/46 (57%) for "Failure" and 1/46 (2%) for "Loss". Patients in the "Failure" stage had a median 3.7-fold higher urinary [TIMP-2]•[IGFBP7] compared to non-AKI subjects (P<0.001). When analyzed for AKI etiology, highest [TIMP-2]•[IGFBP7] values were found in patients with septic shock (P<0.001 vs. non-AKI I+II). Receiver operating characteristic (ROC) curve analyses in the AKI group revealed good performance of [TIMP-2]•[IGFBP7] in predicting 30-day (area under the curve (AUC) 0.79; 95% CI, 0.61-0.97) and 3-month mortality (AUC 0.84; 95% CI, 0.67-0.99) and moderate performance in predicting RRT (AUC 0.67; 95% CI, 0.50-0.84). CONCLUSIONS: This study shows that urinary [TIMP-2]•[IGFBP7] has a good diagnostic performance in predicting adverse outcomes in neonatal and pediatric AKI of heterogeneous etiology.

Antibiotic prophylaxis in the management of percutaneous endoscopic gastrostomy in infants and children.

BACKGROUND: In randomized controlled trials in adult patients the use of prophylactic broad-spectrum antibiotic reduces the number of insertion site and systemic infections, associated with placement of percutaneous endoscopic gastrostomy (PEG) tubes. For pediatric patients no such trials exist. The aim of this study was to assess the value of antibiotic prophylaxis in PEG placement in pediatric patients. METHODS: In a retrospective chart review PEG placement in infants and children performed in a tertiary care center was analyzed. All PEG procedures were performed by an experienced pediatric gastroenterologist using the pull-through technique under general anesthesia. RESULTS: A total of 103 procedures were analyzed; 33 patients received antibiotic prophylaxis and 70 did not. Two (6%) of the patients receiving prophylaxis developed local or systemic infections after PEG placement, whereas seven (10%) without prophylaxis suffered from a PEG-related infection. This difference was not significant on chi-squared test (P = 0.5). Sixty patients had a body temperature >38°C within the first 3 days after the PEG procedure. A total of 77% of these patients had no antibiotic prophylaxis. Mean body temperature differed significantly between patients with and without prophylaxis (37.9°C vs. 38.3°C, respectively; P = 0.02). CONCLUSIONS: The incidence of PEG-related local or systemic infection after PEG-placement was not significantly different between patients with and without antibiotic prophylaxis, but the latter had a significantly higher mean body temperature after the PEG procedure. Taking elevated mean body temperature as a marker for putative bacteremia it is suggested that antibiotic prophylaxis is indicated in all pediatric patients after PEG placement.

Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH).

BACKGROUND: Carcinogenic exocyclic-DNA adducts like 1,N(6)-etheno-2'-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been detected in cancer prone liver diseases including alcoholic liver disease (ALD). In ALD εdA levels correlated significantly with cytochrome P-450 2E1 (CYP2E1) expression which is also induced in non-alcoholic steatohepatitis (NASH). We investigated the occurrence of εdA adducts in children with NASH as a DNA damage marker. METHODS: Liver biopsies from 21 children/adolescents with histologically proven NASH were analysed for hepatic fat content, inflammation, and fibrosis. εdA levels in DNA, CYP2E1-expression and protein bound 4-hydroxynonenal (HNE) were semi-quantitatively evaluated by immunohistochemistry. RESULTS: Among 21 NASH children, εdA levels in the liver were high in 3, moderate in 5, weak in 9 and not elevated in 4 patients. There was a positive correlation between CYP2E1 and protein-bound 4-HNE (r=0.60; P=0.008) and a trend for a positive relationship for CYP2E1 vs. staining intensity of εdA (r=0.45; P=0.06). Inflammatory activity and fibrosis correlated significantly (r=0.49, P=0.023). CONCLUSIONS: Our results demonstrate for the first time the presence of elevated carcinogenic etheno-DNA lesions (εdA) in the majority (17/21) of liver biopsies from young NASH patients. Our data suggest that LPO-derived etheno-adducts are implicated in NASH. Whether these adducts may serve as predictive risk markers in NASH children to develop hepatocellular cancer later in life remains to be investigated.

Alanine aminotransferase elevation in obese infants and children: a marker of early onset non alcoholic Fatty liver disease.

BACKGROUND: Elevated aminotransferases serve as surrogate markers of non-alcoholic fatty liver disease, a feature commonly associated with the metabolic syndrome. Studies on the prevalence of fatty liver disease in obese children comprise small patient samples or focus on those patients with liver enzyme elevation. OBJECTIVES: We have prospectively analyzed liver enzymes in all overweight and obese children coming to our tertiary care centre. PATIENTS AND METHODS: In a prospective study 224 healthy, overweight or obese children aged 1 - 12 years were examined. Body Mass Index-Standard Deviation Score, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transpeptidase were measured. RESULTS: Elevated alanine aminotransferase was observed in 29% of children. 26 % of obese and 30 % of overweight children had liver enzyme elevations. Obese children had significantly higher alanine aminotransferase levels than overweight children (0.9 vs. 0.7 times the Upper Limit of Normal; P = 0.04). CONCLUSIONS: Elevation of liver enzymes appears in 29 % obese children in a tertiary care centre. Absolute alanine aminotransferase levels are significantly higher in obese than in overweight children. Even obese children with normal liver enzymes show signs of fatty liver disease as demonstrated by liver enzymes at the upper limit of normal.

Measurement of real-time tissue elastography in a phantom model and comparison with transient elastography in pediatric patients with liver diseases.

PURPOSE: We aimed to determine the comparability of real-time tissue elastography (RTE) and transient elastography (TE) in pediatric patients with liver diseases. MATERIALS AND METHODS: RTE was performed on the Elasticity QA Phantom Model 049 (Computerized Imaging Reference Systems Company Inc., Norfolk, Virginia, USA), which has five areas with different levels of stiffness. RTE measurements of relative stiffness (MEAN [mean value of tissue elasticity], AREA [% of blue color-coded stiffer tissue]) in the phantom were compared with the phantom stiffness specified in kPa (measurement unit of TE). RTE and TE were performed on 147 pediatric patients with various liver diseases. A total of 109 measurements were valid. The participants had following diseases: metabolic liver disease (n=25), cystic fibrosis (n=20), hepatopathy of unknown origin (n=11), autoimmune hepatitis (n=12), Wilson's disease (n=11), and various liver parenchyma alterations (n=30). Correlations between RTE and TE measurements in the patients were calculated. In addition, RTE was performed on a control group (n=30), and the RTE values between the patient and control groups were compared. RESULTS: The RTE parameters showed good correlation in the phantom model with phantom stiffness (MEAN/kPa, r=-0.97; AREA/kPa, r=0.98). However, the correlation of RTE and TE was weak in the patient group (MEAN/kPa, r=-0.23; AREA/kPa, r=0.24). A significant difference was observed between the patient and control groups (MEAN, P = 5.32 e-7; AREA, P = 1.62 e-6). CONCLUSION: In the phantom model, RTE was correlated with kPa, confirming the presumed comparability of the methods. However, there was no direct correlation between RTE and TE in patients with defined liver diseases under real clinical conditions.

Normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children.

PURPOSE: To define normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children. METHODS: RTE was performed on 91 children and adolescents by two experienced observers (female, n = 43; male, n = 48) and in two age groups (0-10 years, n = 45; 11-20 years, n = 46). Hepatopathies were excluded clinically by extensive laboratory testing and by ultrasound. RTE provides a histogram from a region of interest (ROI) in the liver representing the degree of stiffness of the liver. The distribution of the colors in the histogram corresponds to organ elasticity. By calculating the mean of stiffness values, a numerical value is expressed in arbitrary units (a.u.) representing the mean elasticity of the liver (MEAN). Additionally, the percentage values of relatively stiffer areas (color coded in blue) in the ROI can be calculated (%AREA). A Mann-Whitney U test was performed for these two parameters according to gender. The reproducibility of these values was determined with an intraclass correlation coefficient (ICC) test on another group of 18 healthy volunteers. RESULTS: The median elasticity was 106 a.u. Gender did not have an influence on the parameters (MEAN: p = 0.052; %AREA: p = 0.051). Age-specific analyses did not yield any significant difference between the two age groups for either of the two analyzed parameters (MEAN: p = 0.059; %AREA: p = 0.058). The ICC test demonstrated a moderate agreement for MEAN (ICC = 0.582) and %AREA (ICC = 0.659). CONCLUSION: Real-time elastography is a new sonography-based method and may be used as a supportive analysis to assess liver parenchyma elasticity in children, especially when fibrosis is suspected. We measured RTE normal values in children as reference data.

Real-time tissue elastography (RTE) for noninvasive evaluation of fibrosis in liver diseases in children in comparison to liver biopsy.

PURPOSE: To determine the value of real-time tissue elastography (RTE) in pediatric liver diseases in comparison to liver biopsy. METHODS: RTE was performed on 34 patients (♀, n = 17; ♂, n = 17; range 0-21 years) with various acute and chronic liver diseases: autoimmune hepatitis (n = 5), liver transplantation (n = 5), Wilson's disease (n = 4), hepatopathy of unknown origin (n = 4), unclear cholestatic hepatitis (n = 2), thalassemia major (n = 2), glycogenosis (n = 2), hereditary fructose intolerance (n = 1), alpha-1-antitrypsin deficiency (n = 1), diabetes mellitus type 1 (n = 1), chronic intestinal pseudo-obstruction (n = 1), primary sclerosing cholangitis (n = 1), hepatitis B (n = 1), cirrhosis of unknown origin (n = 1), drug-induced hepatopathy (n = 1), unexplained transaminase elevation (n = 1), and nonalcoholic steatohepatitis (n = 1). Included children were biopsied. RTE was performed on a control group (n = 30; ♀, n = 15; ♂, n = 15). The mean value of strain (MEAN) in arbitrary units and the ratio of blue color-coded harder tissue (AREA) were calculated based on an elasticity histogram of the selected region of interest in liver parenchyma. They were compared with the histologically defined grade of liver fibrosis. RESULTS: In comparison to the scoring systems, a moderate correlation was observed for MEAN and AREA by excluding the F0 patients [MEAN r = -0.575 to -0.645, AREA r = 0.545-0.607 (p < 0.05)]. Differentiation of the control group and low-grade fibrosis (F1) from high-grade fibrosis (F2-4) was significantly possible (p values <0.001 at 5 % significance level). CONCLUSION: RTE parameters enable a possible differentiation of high fibrosis; however, their correlation with fibrosis stage was moderate. RTE seems to be a promising method in liver fibrosis grading in children.

Efficacy and safety of oral chelators in treatment of patients with Wilson disease.

BACKGROUND & AIMS: Wilson disease is a genetic copper storage disorder that causes hepatic and neurologic symptoms. Chelating agents (D-penicillamine, trientine) are used as first-line therapies for symptomatic patients, but there are few data from large cohorts. We assessed the safety of D-penicillamine and trientine therapy and outcomes of patients with Wilson disease. METHODS: We performed a retrospective analysis of data on 380 patients with Wilson disease from tertiary care centers in Germany and Austria, and 25 additional patients from the EUROWILSON registry. Chelator-based treatment regimens were analyzed for their effect on neurologic and hepatic symptoms and for adverse events that led to discontinuation of therapy (Kaplan-Meier estimation; data were collected for a mean of 13.3 y after therapy began). RESULTS: Changes in medication were common, resulting in analysis of 471 chelator monotherapies (326 patients receiving D-penicillamine and 141 receiving trientine). Nine of 326 patients treated with D-penicillamine and 3 of 141 patients given trientine underwent liver transplantation. Adverse events leading to discontinuation of treatment were more frequent among those receiving D-penicillamine than trientine (P = .039). Forty-eight months after therapy, hepatic deterioration was reported in only 4 of 333 patients treated initially with a chelating agent. Hepatic improvements were observed in more than 90%, and neurologic improvements were observed in more than 55%, of therapy-naive patients, and values did not differ significantly between treatments. However, neurologic deterioration was observed less frequently in patients given D-penicillamine first (6 of 295) than those given trientine first (4 of 38; P = .018). CONCLUSIONS: Chelating agents are effective therapies for most patients with Wilson disease; D-penicillamine and trientine produce comparable outcomes, although D-penicillamine had a higher rate of adverse events. Few patients receiving chelation therapy had neurologic deterioration, which occurred more frequently in patients who received trientine.

Feasibility study and control values of transient elastography in healthy children.

Transient elastography (TE) is a new technique for the non-invasive assessment of liver fibrosis. The degree of fibrosis is equivalent to the liver stiffness measured in kilopascal (kPa). It is frequently used in adult patients with a mean normal stiffness of 4.4-5.5 kPa. Since 2008, liver stiffness can be measured even in small children and infants following the availability of a new probe with a smaller diameter (S-probe 5 mm) than the regular probe (M-probe 7 mm). We report control values for healthy children between 0 and 18 years and investigated the feasibility of this technique in a pediatric population. For control values, TE was performed in infants and children after exclusion of liver disease by medical history, clinical examination, blood investigation, and abdominal ultrasound. For feasibility analyses the results of all TE performed in our clinic were analyzed irrespective of the underlying disease. Liver stiffness was measured with the S-probe (thorax diameter <45 cm (S1) or 45-75 cm (S2)) and the M-probe (thorax diameter >75 cm) according to the manufacturer's recommendations. A total of 240 healthy children were analyzed to establish control values. The median liver stiffness was 4.7 kPa resulting in an upper limit of normal of 6.47 kPa. Median values of stiffness were significantly age dependent with 4.40, 4.73, and 5.1 kPa in children 0-5, 6-11, and 12-18 years (p = 0.001) while the interquartile range decreased with age (0.8, 0.7, and 0.6 kPa). The resulting upper limit of normal (median plus 1.64 times standard deviation) was 5.96, 6.65, and 6.82 kPa. Girls between 11 and 18 years showed a significantly lower median stiffness than boys of the same age (4.7 vs. 5.6 kPa; p < 0.005). Feasibility was tested in 975 consecutive liver stiffness measurements (LSM) in children 0-18 years of age. Patients with invalid LSM were significantly younger than those with valid LSM (5.8 vs. 9.7 years, p < 0.0001), showed a significantly higher stiffness (10.2 vs. 6.17, p < 0.0001), and examinations took significantly longer (202 vs. 160 s, p < 0.0001). TE is technically possible in children of all age groups. The upper limit of normal increases significantly with age. Due to movement artifacts the measurement is reliable from the age of 6 without sedation. In younger children the number of invalid measurements increases significantly. Further studies are needed to asses the value of TE in the diagnosis and follow-up of liver disease in pediatric hepatology.

High urgency liver transplantation in ornithine transcarbamylase deficiency presenting with acute liver failure.

OTCD can present with ALF at any age. Under adequate therapy symptoms resolve quickly. We report a three-yr-old girl with the manifestation of an OTCD as ALF. Despite adequate pharmacotherapy and protein restriction, the patient deteriorated and developed hepatic encephalopathy. A high urgency liver transplantation was performed and the patient recovered completely. We conclude that in patients with ALF urea cycle defects in general and OTCD in particular should be considered as differential diagnosis. Patients should be managed in a center that has the capacity for an emergency liver transplantation.

Effects of budesonide inhalation on energy expenditure, somatic growth and salivary cortisol levels in preterm infants with chronic lung disease.

BACKGROUND: We hypothesized that the use of inhaled budesonide (BUD) would alter somatic growth by increasing energy expenditure (EE) in premature infants with chronic lung disease (CLD). METHODS: A prospective study was conducted of the effect of BUD on EE, growth and salivary cortisol excretion in infants with CLD who required supplemental oxygen and were treated with inhaled BUD for 4 weeks according the severity of their CLD, or without BUD treatment. Infants were compared with a healthy control group matched for gestational age. EE, anthropometric measures and salivary cortisol levels were examined before, during and after BUD treatment. RESULTS: A total of 30 spontaneously breathing premature infants were enrolled in the study. EE in CLD (BUD) and CLD (no BUD) patients were greater than EE in healthy preterm infants (p < 0.01) at the study time points. Growth did not differ between the groups. Salivary cortisol levels of treated infants were significantly lower when compared with the levels of nontreated infants. CONCLUSION: The administration of inhaled BUD in preterm infants with CLD was associated with an increase in EE, a suppression of endogenous cortisol production and with no effect on duration of supplemental oxygen, but did not compromise their somatic growth.

Energy expenditure in neonates with Down syndrome.

Resting energy expenditure was measured in term neonates with Down syndrome during the first week of life and compared with healthy neonates. Infants with Down syndrome expended 14% fewer calories than did healthy infants of the same age.