Is Doppler echocardiography useful for estimating left ventricular filling pressures in pediatric heart transplant recipients?

LV E/E′ ratio obtained using Doppler echocardiography is considered a surrogate for LV filling pressure in adults but has performed poorly in children. We hypothesized that LV E/E′ ratio Z‐score, adjusted for age, will relate more strongly to LV filling pressures than LV E/E′ ratio in pediatric HT recipients. We analyzed 751 echocardiograms performed within 24 hours of a heart catheterization in 122 pediatric HT recipients (median age at HT 13 years, median 6 studies per patient). The primary end‐point was PCWP, assessed both as a continuous and a binary variable. Associations with LV E/E′ ratios and z‐scores were assessed using generalized estimating equations models. PCWP, LV E/E′ ratios (using E′ from LV free wall, septum, and their average), and LV E/E′ ratio Z‐scores, all declined over time after HT. LV E/E′ ratios and their Z‐scores were significantly associated with PCWP assessed as a continuous variable (P < 0.001 for all); however, the relationship was weak (R² range, 0.083 to 0.121). LV E/E′ ratios and their Z‐scores were also significantly associated with PCWP as a binary variable (P < 0.001 for all) but with only modest ability to discriminate PCWP ≥15 mm Hg (c‐statistic range, 0.660 to 0.695). The association between LV E/E′ ratio and PCWP in pediatric HT recipients is modest. Using a LV E/E′ ratio Z‐score did not result in significantly improved association with PCWP. Current Doppler echocardiographic methods are unreliable for estimating LV filling pressures in pediatric HT recipients.     

Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia

Background

Escherichia coli asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity develops in up to 30% of patients. We assessed the nadir enzyme activity and tolerability of Erwinia asparaginase, an alternative preparation, in E. coli asparaginase‐allergic patients.

Patients and Methods

Between 2000 and 2002, 215 children with newly diagnosed ALL were enrolled on Dana‐Farber Cancer Institute ALL Consortium Protocol 00‐01 and were to receive 30 weekly doses of intramuscular E. coli asparaginase. If E. coli asparaginase allergy developed, patients were switched to twice‐weekly intramuscular Erwinia asparaginase (25,000 IU/m²). Nadir serum asparaginase activity (NSAA) was measured every 3 weeks.

Results

Forty‐two patients (20%) developed E. coli asparaginase allergy and switched to Erwinia. Of 38 patients with evaluable samples, 34 (89%) Erwinia‐treated patients had at least one therapeutic NSAA (≥0.1 IU/ml). The median NSAA was 0.247 IU/ml 3 days and 0.077 IU/ml 4 days after an Erwinia dose. Associated toxicities included allergy in 14 (33%) and pancreatitis in 3 patients (7%). At a median follow‐up of 5.4 years, event‐free survival (±standard error) of the 42 patients who switched to Erwinia was 86 ± 5% compared with 81 ± 3% for the 170 patients without E. coli asparaginase allergy (P = 0.55).

Conclusions

Twice‐weekly Erwinia asparaginase was well tolerated and achieved a therapeutically effective NSAA in most E. coli asparaginase‐allergic patients. Development of E. coli allergy and subsequent treatment with twice‐weekly Erwinia did not adversely impact event‐free survival. Erwinia asparaginase should be considered for E. coli asparaginase‐allergic patients. Pediatr Blood Cancer 2010;54:199–205. © 2009 Wiley‐Liss, Inc.     

Correlation of vitamin A nutritional status on alpha‐tocopherol in the colostrum of lactating women

The adequate supply of vitamins A and E to newborns is essential. However, factors such as maternal nutritional status and nutrient interaction may limit its bioavailability. The aim of this study was to establish nutritional status for vitamins A and E and evaluate the correlation of retinol on colostrum alpha‐tocopherol in lactating women. A total of 103 lactating women were recruited at a Brazilian public maternity hospital. Fasting serum and colostrum samples were collected in the immediate post‐partum. Retinol and alpha‐tocopherol levels were determined by high‐performance liquid chromatography and nutritional status for these vitamins was defined from specific cut‐off points for serum and colostrum. Mean serum and colostrum retinol (1.49 µmol L^?1, 2.18 µmol L^?1) and alpha‐tocopherol (26.4 µmol L^?1, 26.1 µmol L^?1) indicated satisfactory biochemical status. However, we found a prevalence of subclinical deficiency of vitamin A and vitamin E in serum (15.5% and 16%) and colostrum (50% and 60%). Lactating women with serum retinol ≥ 1.05 µmol L^?1 showed an inverse correlation between serum retinol and alpha‐tocopherol concentration in the colostrum (P = 0.008, r = ?0.28). This association was not observed in serum level < 1.05 µmol L^?1. The nutritional status of lactating women for vitamins A and E was adequate, although there is a risk of subclinical deficiency. The negative correlation of serum retinol on alpha‐tocopherol concentration in the colostrum must be carefully evaluated in situations of vitamin A supplementation, because alpha‐tocopherol bioavailability in maternal milk may be compromised.     

Depression and anxiety levels of the mothers of children and adolescents with left ventricular assist devices

Ozbaran B, Kose S, Yagdi T, Engin C, Erermis S, Yazici KU, Noyan A, Ozbaran M. Depression and anxiety levels of the mothers of children and adolescents with left ventricular assist devices. Abstract: VADs have been used to provide treatment for end‐stage heart failure. Parents may feel overwhelmed with the VAD regimes responsibility and be affected from this process beside children. In this study, we aimed to evaluate the depressive and anxiety symptoms of mothers of the first eight children equipped with a VAD in Turkey. The mothers of eight pediatric patients living with VADs were filled BDI and STAI at first month of VAD implantation (E.I) and secondly six months after their first evaluation (E.II). In E.I, the BDI mean score of mothers was 20.87, in E.II 14.37. STAI‐S mean score was 53.37 in E.I and 43.62 in E.II. The Wilcoxon nonparametric‐paired t‐test revealed significant difference between baseline and end‐point STAI‐S scores (Z: ?2.035; p: 0.042), and for BDI scores (Z, ?1.965; p, 0.049). Prolonged usage of VAD may increase distress in parents. Psychiatric evaluation and support of the primary caregiver is important for the well‐being of the pediatric patients.     

THIS ARTICLE HAS BEEN RETRACTED: Acalculous candidal cholecystitis after pediatric renal transplant

Grosser J, Solomon H, Sotelo‐Avila C. Acalculous candidal cholecystitis after pediatric renal transplant.
Pediatr Transplantation 2011: 15: E71–E75. © 2010 John Wiley & Sons A/S. Abstract: AAC caused by Candida is an uncommon entity usually seen in the critically ill. Here, we present the case of an 18‐month‐old renal transplant patient who developed candidal AAC during the post‐operative period. Previous articles have addressed acalculous cholecystitis secondary to a variety of causes, or addressed a wide variety of Candida infections in the biliary tract, but this is the first discussion of cholecystitis caused by Candida without confounding factors such as biliary calculi or multiple pathogens. After the discussion of our patient’s case, we also reviewed the English‐language literature regarding candidal AAC and discussed diagnosis, treatment, and mortality.     

Concentrations of alpha‐ and gamma‐tocopherols in human breast milk during the first months of lactation and in infant formulas

The aim of this study was to determine the concentrations of alpha‐ and gamma‐tocopherols in human breast milk samples from different periods of lactation and to compare them with tocopherol content in commercially available formulas for infants at corresponding ages. The study included 93 breast milk samples obtained on the 2nd (colostrum, n = 17), 14th (n = 30), 30th (n = 27) and 90th day of lactation (n = 19), along with 90 samples of commercially available initial and follow‐on infant formulas. Concentrations of tocopherols were determined using normal‐phase high‐performance liquid chromatography. Depending on the stage of lactation, human breast milk contained 2.07–9.99 mg L^?1 of alpha‐tocopherol and 0.22–0.60 mg L^?1 of gamma‐tocopherol. Breast milk concentrations of alpha‐tocopherol decreased with the time of lactation, while significant differences in gamma‐tocopherol concentration were observed only between the 14th and 30th day of lactation. There was no significant correlation between the dietary intake of vitamin E and its estimated breast milk concentration, also in women who declared vitamin supplementation. Compared with colostrum, infant formulas were characterised by significantly lower concentrations of alpha‐tocopherol and vitamin E. This finding indicates the need of additional vitamin E supplementation of bottle‐fed infants during the initial 2–3 days of life.     

Citrullinaemia type I: a common mutation in the Pacific Island population

Aim: The aim of this study was to develop and apply a mutation screening protocol for the ASS1 gene in order to confirm the diagnosis of citrullinaemia type I in neonates with elevated citrulline on expanded newborn screening (E‐NBS). Methods: Three patients with an elevated citrulline level were identified via routine E‐NBS between January and October 2008. Analysis of the ASS1 gene using a polymerase chain reaction and sequencing‐based method was successfully applied to all three patients, together with a rapid mutation‐specific detection method. Their clinical progress was followed for 16–22 months. Results: All three patients were homozygous for a previously reported missense mutation, c.787G>A (p.Val263Met), associated with a mild or asymptomatic clinical course. Conclusions: As a consequence of E‐NBS, an increasing number of neonates with elevated citrulline of uncertain clinical significance are being identified. Rapid sequence analysis of the ASS1 gene can be used to confirm citrullinaemia type I and, increasingly, to infer phenotypic severity. Homozygosity for the same mutation was found in all three patients despite non‐consanguinity and variable Pacific Island origin. These data suggest that this mutation may be relatively prevalent in these ethnic groups and imply a possible founder effect.     

Intestinal microbiota in allergic and nonallergic 1‐year‐old very low birth weight infants after neonatal glutamine supplementation

Aim: Previously, glutamine‐enriched enteral nutrition in very low birth weight infants (VLBW) decreased the incidence of atopic dermatitis at age 1 year. The aim of this study was to determine whether this effect is related to changes in intestinal bacterial species that are associated with allergy, such as bifidobacteria, clostridium histolyticum, clostridium lituseburense (Chis/lit group) and Escherichia coli at age 1 year. Methods: Eighty‐nine infants were eligible for this follow‐up study, conducted at a Tertiary care hospital. Bifidobacteria, Chis/lit group and E. coli were measured by fluorescent in situ hybridization in faecal samples collected at age 1 year. Information on allergic and infectious diseases was previously determined by questionnaire. Results: Seventy‐two of 89 (81%) infants were participated. Prevalence of all studied species was not different between glutamine‐supplemented and control groups. Allergic infants were less frequently colonized with bifidobacteria than nonallergic infants (p = 0.04). Between neonatal period and 1 year, prevalence of bifidobacteria was increased (p < 0.001), of Chis/lit group was unchanged (p = 0.84), and of E. coli was decreased (p < 0.001). Conclusion: The beneficial effect of glutamine‐enriched enteral nutrition on the incidence of atopic dermatitis in the first year of life in VLBW infants is not related to changes in bifidobacteria, Chis/lit group or E. coli. Allergic VLBW infants are less frequently colonized with bifidobacteria compared to nonallergic VLBW infants.     

The dopamine receptor D4 7‐repeat allele and prenatal smoking in ADHD‐affected children and their unaffected siblings: no gene–environment interaction

Background: The dopamine receptor D4 (DRD4) 7‐repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G×E) interaction of the DRD4 7‐repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7‐repeat allele differs between ADHD affected and unaffected children. Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7‐repeat allele and smoking during pregnancy in 539 ADHD‐affected children and their 407 unaffected siblings, aged 6–17 years. Results: There was some evidence pointing to differential effects of the DRD4 7‐repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G×E interactions. Conclusion: Despite the large sample size, no G×E interactions were found. The impact of the DRD4 7‐repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater‐specific behaviors.     

Effect of vitamin E treatment on the oxidative damage occurring in Henoch-Schönlein purpura

Aim: To evaluate the role of reactive oxygen molecules (ROMs) in the pathogenesis of Henoch‐Schonlein purpura and the effect of vitamin E on oxidative damage. ROMs have been suggested to contribute in many pathological conditions including renal diseases and vasculitis. Methods: The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) as antioxidant enzymes were measured, and the level of malondialdehyde (MDA) as an indicator of lipid peroxidation in 27 children with Henoch‐Schönlein purpura at the onset of the disease and during the remission period. The results of this study were compared with those of 11 healthy children studied as a control group. Results: With regard to all the oxidative damage parameters such as SOD, GSH‐Px and MDA, significant differences were detected between the patients and the control group in both the acute and remission periods. But no such differences were detected between patients with and those without renal involvement. In 15 patients receiving vitamin E treatment, oxidative damage parameters and clinical course showed no improvement despite significant increases in plasma vitamin E levels. Conclusion: Oxidative damage and lipid peroxidation may play an important part in the pathogenesis of Henoch‐Schonlein purpura but vitamin E given after initiation of lipid peroxidation, which is the last phase of cellular damage, is of no use in breaking down the oxidative chain reactions that have already been triggered.     

De novo phyllodes tumor in an adolescent female after liver transplantation

Cheng F, Qin J‐J, Yu M‐N, Zhang F, Li X‐C, Sun B‐C, Kong L‐B, Wang X‐H. De novo phyllodes tumor in an adolescent female after liver transplantation.
Pediatr Transplantation 2011: 15:E12–E14. © 2009 John Wiley & Sons A/S. Abstract: Phyllodes tumor of the breast is a rare disease constituting 0.3–0.9% of all breast neoplasms. Occurring mainly in females aged 35 to 55 yr, the disease is especially rare among adolescent females. There is no published literature about de novo phyllodes tumor after liver transplantation. Here we describe a case of de novo phyllodes tumors in an adolescent female after liver transplantation from a living donor for Wilson disease.     

Effect of Bifidobacterium administration on very‐low‐birthweight infants

Background: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very‐low‐birthweight (VLBW) infants. Methods: We conducted a single‐center prospective pilot study. Thirty‐six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. Results: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7–13] days and 11 [10–15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real‐time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. Conclusion: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.     

Catechol-O-methyltransferase Val158 Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis

Background: Recently, first evidence has been reported for a gene–parenting interaction (G × E) with regard to adolescent alcohol use. The present investigation set out to extend this research using the catechol‐O‐methyltransferase (COMT) Val¹⁵⁸Met polymorphism as a genetic susceptibility factor. Moreover, the current study examined whether a potential G×E would be consistent with one of two models of gene–environment interplay (genetic vulnerability vs. differential susceptibility). Methods: Data were collected as part of an ongoing epidemiological cohort study following the outcome of early risk factors from birth into adulthood. Two hundred and eighty‐five participants (130 males, 155 females) were genotyped for the COMT Val¹⁵⁸Met polymorphism and were administered an alcohol interview, providing measures of current frequency and amount of drinking at ages 15 and 19 years. Information on three dimensions of perceived parenting behavior was obtained from the 15‐year‐olds. Results: Adolescents homozygous for the Met allele showed higher drinking activity at age 19 years when their parents had engaged in less supervision or were less involved, while their drinking activity was reduced under conditions of favorable parenting. No such relationship was found in individuals carrying the Val allele. Conclusions: The present findings correspond with the pattern of results predicted by the differential susceptibility hypothesis, suggesting that environmental variation would have a greater impact in individuals carrying a genetic susceptibility such that, in this group, exposure to negative environmental conditions would result in more adverse outcomes and the experience of favorable conditions would lead to more positive outcomes.     

Luminex‐based virtual crossmatching facilitates combined third‐time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody‐mediated cardiac allograft rejection

Deutsch M‐André, Kauke T, Sadoni S, Kofler S, Schmauss D, Bigdeli AK, Weiss M, Reichart B, Kaczmarek I. Luminex‐based virtual crossmatching facilitates combined third‐time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody‐mediated cardiac allograft rejection.
Pediatr Transplantation 2010: 14:E96–E100. © 2009 John Wiley & Sons A/S. Abstract: Allosensitization represents a major obstacle to successful re‐transplantation since circulating antibodies can elicit antibody‐mediated rejection episodes with subsequent graft failure. Since sensitization is primarily considered a contraindication to transplantation the duration for patients waiting for a suitable donor organ to become available is considerably prolonged. Herein, we report on the successful application of a Luminex‐based virtual crossmatch approach to facilitate combined third‐time cardiac and de novo renal transplantation in a sensitized patient with sustained antibody‐mediated cardiac allograft rejection.     

Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli‐Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia

Background

Erwinia asparaginase is antigenically distinct from E.coli‐derived asparaginase and may be used after E.coli‐derived asparaginase hypersensitivity. In a single‐arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV‐Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli‐derived asparaginase.

Patients and Methods

Between 2012 and 2013, 30 patients (age 1–17 years) enrolled from 10 centers. Patients received IV‐Erwinia, 25,000 IU/m²/dose on Monday/Wednesday/Friday, for 2 consecutive‐weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase‐related toxicities.

Results

Twenty‐six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63–95%) 48 hr post‐dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22–66%) 72 hr post‐dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV‐Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%.

Conclusions

IV‐Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically‐effective NSAA (≥0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post‐dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated. Pediatr Blood Cancer 2015. © 2015 Wiley Periodicals, Inc.     

Association between maternal vitamin E status and alpha‐tocopherol levels in the newborn and colostrum

Vitamin E is important because of its antioxidant activity in situations of oxidative stress, especially postnatally. Hence, the objective was to verify whether maternal alpha‐tocopherol level is associated with the alpha‐tocopherol levels of the newborn and colostrum. This is a cross‐sectional study of 58 women and their term newborns from a public hospital. Blood and colostrum were collected to measure alpha‐tocopherol levels by high‐performance liquid chromatography. Mothers with serum alpha‐tocopherol levels <16.2 mmol L^?1 and newborns <11.6 mmol L^?1 were indicative of deficiency or low levels. Mothers were divided into two groups: <16.2 mmol L^?1 and those with levels ≥16.2 mmol L^?1. The mean (95% confidence interval) serum alpha‐tocopherol levels of mothers, umbilical cords and colostrum were 28 (24–32), 6 (5–8) and 39 mmol L^?1 (32–45), respectively (P < 0.001); 19% of the women and 90% of the newborns had low alpha‐tocopherol levels. Maternal alpha‐tocopherol level was associated with that of the umbilical cord. Newborns from mothers at risk of deficiency had low alpha‐tocopherol levels (P < 0.001). Colostrum levels of vitamin E were not influenced by maternal serum. Maternal deficiency influenced the vitamin E level of the umbilical cord but does not in the colostrum, evidencing distinct transfer mechanisms via the mammary gland.     

Anaplastic oligodendroglioma in an adolescent with Lynch syndrome

Lynch syndrome (hereditary non‐polyposis colorectal cancer; HNPCC) is an autosomal dominant cancer predisposition syndrome with high penetrance. It is caused by heterozygous germline mutations in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. Carriers are at high‐risk for developing colorectal carcinomas, as well as various extracolonic malignancies. This case report describes a 15 year‐old male with a confirmed germline mutation of MSH2 and early onset anaplastic oligodendroglioma. The patient's tumor showed loss of expression of MSH2 and MSH6 proteins with normal microsatellite stability. The immunohistochemical staining pattern provided strong evidence to support the inclusion of anaplastic oligodendroglioma as part of the spectrum of tumors found in Lynch syndrome. Pediatr Blood Cancer 2013; 60: E13–E15. © 2012 Wiley Periodicals, Inc.