HHV-6 Specific T-Cell Immunity in Healthy Children and Adolescents.

Objective: Primary infection with human herpes virus 6 (mainly HHV-6B) commonly occurs in the first 2 years of life leading to persistence and the possibility of virus reactivation later in life. Consequently, a specific cellular immune response is essential for effective control of virus reactivation. We have studied cell-mediated immune response to HHV-6 (U54) in healthy children and adolescents. Materials and Methods: By flow cytometry, the amount of cytokine (interferon gamma-IFN- γ, interleukin 2-IL-2, tumor necrosis factor alpha-TNF-α) secreting T-cells were measured after 10 days of pre-sensitization and 6 h of re-stimulation with mixtures of pooled overlapping peptides from U54, staphylococcal enterotoxin B (SEB, positive control), or Actin (negative control) in healthy children and adolescents without any underlying immune disorder or infectious disease. Results: All individuals showed a virus-specific response for at least one cytokine in either CD4+ or CD8+ cells. Percentages of individuals with HHV-6-specific TNF-α response in CD4+ (48% of individuals) as well as CD8+ (56% of individuals) were always the highest. Our data show significantly higher frequencies of HHV-6-specific TNF-α producing CD8+ T-cells in individuals older than 10 years of life (p = 0.033). Additionally, the frequency of HHV-6 specific TNF-α producing CD8+ T-cells positively correlated with the age of the individuals. Linear regression analysis showed a positive relation between age and frequency of HHV-6-specific TNF-α producing CD8+ T-cells. Conclusion: Results indicate that T-cell immune response against HHV-6 is commonly detectable in healthy children and adolescents with higher frequencies of antigen-specific T-cells in older children and adolescents possibly reflecting repeated stimulation by viral persistence and subclinical reactivation.

The diagnostic value of hepcidin to predict the presence and severity of appendicitis in children.

BACKGROUND: The aim of this study was to determine the diagnostic capacity of hepcidin in pediatric acute appendicitis and its accuracy as a predictor of the severity of appendicitis. MATERIALS AND METHODS: In children with appendicitis (n = 39), leukocytes, platelet count, and the serum levels of C-reactive protein (CRP) and hepcidin were compared to a control group (n = 25) of patients with unspecific abdominal pain. Additionally, parameters were compared between children with simple (n = 17) and complicated appendicitis (n = 22). Receiver operation characteristic analyses of the different parameters were performed and the areas under the curve (AUCs) calculated. RESULTS: Leukocytes and serum hepcidin levels were significantly higher in children with acute appendicitis versus control group (13.7 ± 5.7 versus 9.8 ± 3.9 G/L, P = 0.005 and 31.3 ± 21.7 versus 20.4 ± 14 ng/mL, P = 0.039). AUCs for hepcidin, leukocytes, and CRP were 0.654, 0.711, and 0.619, respectively. Complicated appendicitis was associated with significantly higher hepcidin concentrations compared to simple appendicitis (38.5 ± 17.6 ng/mL versus 21.6 ± 23.4 ng/mL, P < 0.001). A combination of leukocytes, CRP, and hepcidin had the highest AUC (0.914) to predict complicated appendicitis. CONCLUSIONS: Increased serum levels of hepcidin were found in children with appendicitis compared to controls. While hepcidin was useful to identify patients with complicated appendicitis as it does not seem appropriate to distinguish between simple appendicitis and other causes for acute abdominal pain.

The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study.

Proton pump inhibitors (PPIs) are the standard therapy for gastroesophageal reflux disease. In adults, PPI treatment is associated with Clostridium difficile infections (CDI). In contrast to adults the microbiome of infants develops from sterility at birth toward an adult-like profile in the first years of life. The effect of PPIs on this developing microbiome has never been studied. The aim of the present study was to determine the effect of oral PPIs on the fecal microbiome in infants with gastroesophageal reflux disease (GERD). In this prospective longitudinal study 12 infants with proven GERD received oral PPIs for a mean period of 18 weeks (range 8-44). Stool samples were collected before ("before PPI") and 4 weeks after initiation of PPI therapy ("on PPI"). A third sample was obtained 4 weeks after PPI discontinuation ("after PPI"). The fecal microbiome was determined by NGS based 16S rDNA sequencing. This trial was registered with clinicaltrials.gov (NCT02359604). In a comparison of "before PPI" and "on PPI" neither α- nor ß-diversity changed significantly. On the genus level, however, the relative abundances showed a decrease of Lactobacillus and Stenotrophomonas and an increase of Haemophilus. After PPI therapy there was a significant increase of α- and ß-diversity. Additionally, the relative abundances of the phyla Firmicutes, Bacteroidetes, and Proteobacteria were significantly changed and correlated to patients' age and the introduction of solid foods. PPI treatment has only minor effects on the fecal microbiome. After discontinuation of PPI treatment the fecal microbiome correlated to patients' age and nutrition.

Congenital Infantile Fibrosarcoma Causing Intestinal Perforation in a Newborn.

Congenital infantile fibrosarcoma (CIF) is a rare malignant mesenchymal tumor and only 14 cases have been reported with gastrointestinal manifestation. We report about a female newborn delivered per emergency cesarean section at 34 weeks of gestation. Postnatally, she rapidly developed an acute abdomen and sonographic evidence of intestinal perforation requiring laparotomy on the first day of life. A perforated 2 × 3 cm sized spherical tumorous structure of the jejunum was identified. Due to unknown histopathology at this point and unclear resectional margins, she received a temporary ileostomy, which was closed two months later. Histopathology revealed a congenital intestinal fibrosarcoma without the characteristic ETV6-NTRK3 fusion transcript. In conclusion, this rare tumor must be considered as differential diagnosis of intestinal perforations in newborns.

Neuroblastoma causes alterations of the intestinal microbiome, gut hormones, inflammatory cytokines, and bile acid composition.

OBJECTIVE: To assess the effect of neuroblastoma (NB) on the intestinal microbiome, metabolism, and inflammatory parameters in a murine model. MATERIALS AND METHODS: Athymic Hsd:Fox1nu mice received subperitoneal implantation of human NB cells (MHH-NB11) (tumor group, TG) or culture medium (sham group). Following 10 weeks of tumor growth, all animals were sacrificed to collect total white adipose tissue (WAT). Luminex assays were performed for gut hormone and inflammation marker analysis. Bile acids were measured by high-performance liquid chromatography-mass spectrometry in feces and serum. The microbiome of the ileal content was determined by 16S rDNA next-generation sequencing. RESULTS: At 10 weeks, tumors masses in the TG reached a mean weight of 1.10 g (interquartile range 3.45 g) associated with a significant reduction in WAT. Furthermore, in the TG, there was a marked reduction in leptin and an increase in glucagon-like peptide 1 serum levels. Moreover, the TG mice displayed a pro-inflammatory profile, with significant increases in monocyte chemotactic protein 1, tumor necrosis factor alpha, and interleukin-10. Lithocholic acid, deoxycholic acid, and ursodeoxycholic acid were significantly decreased in the stool of TG mice. Significant alterations of the intestinal microbiome were found in the ileal contents of the TG. CONCLUSIONS: The present study provides a first glimpse that human NB in a murine model induces tumor cachexia associated with alterations in metabolic and inflammatory parameters, as well as changes in the intestinal microbiota. Since the intestinal microbiome is known to contribute to the host's ability to harvest energy, a favorable modulation of the intestinal microbiome in tumor patients could potentially represent a novel therapeutic target to prevent tumor-associated cachexia.

Judet type-IV radial neck fractures in children: Comparison of the outcome of fractures with and without bony contact.

Background and purpose - Heavily displaced radial neck fractures in children are sometimes associated with poor outcome. A substantial number of these fractures require open reduction. We hypothesized that Judet type-IV fractures with a completely displaced radial head would result in a worse outcome than radial neck fractures with remaining bony contact. Patients and methods - We analyzed 19 children (median age 9.7 (4-13) years) who were treated for Judet type-IV radial neck fractures between 2001 and 2014. The outcome was assessed at the latest outpatient visit using the Linscheid-Wheeler score at a median time of 3.5 (1-8) years after injury. The patients were assigned either to group A (9 fractures with remaining bony contact between the radial head and the radial neck) or to group B (10 fractures without any bony contact). Results - The 2 groups were similar concerning age and sex. The rate of additional injuries was higher in group B (7/10 vs. 1/9 in group A; p = 0.009). The rate of open reduction was higher in group B (5/10 vs. 0/9 in group A; p = 0.01). Poor outcome was more common in group B (4/10 vs. 0/9 in group A; p = 0.03). In group B, the proportion of children with poor outcome (almost half) was the same irrespective of whether open or closed reduction had been done. Interpretation - The main causes of unfavorable results of radial neck fracture in children appear to be related to the energy of the injury and the amount of displacement-and not to whether open reduction was used.

Huge Congenital Segmental Dilatation of the Sigmoid Colon in a Neonate: A "Rarity to Meet" and a "Challenge to Treat".

Only ten cases of neonatal congenital segmental dilatation (CSD) of the colon have been described so far. We present a full-term female newborn with trisomy 21, ventricular septal defect, and gross abdominal distension. Plain abdominal radiographs revealed a huge cystic lesion occupying the left hemiabdomen. Upon laparotomy on day 4 a CSD of the distal sigmoid and proximal rectum was confirmed and resected. The proximal colon was exteriorized and the distal part closed as a Hartmann pouch. Histology confirmed a huge segmental dilatation of the sigmoid without dysganglionosis or pseudodiverticula, but normal intestinal architecture. After correction of the ventricular septal defect a low rectal end-to-end anastomosis could be performed at an age of 5 months. The postoperative course was uneventful. CSD of the sigmoid colon is extremely "rare to meet" and a "challenge to treat" in the newborn period, but clinical awareness of this entity prompts pediatric surgical success.