See Covering the Cover synopsis on 269. See editorial on page 295. BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn's disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier. METHODS: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n ¼ 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n ¼ 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12. RESULTS: Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P ¼ .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68-115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P ¼ .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P ¼ .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34-10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria. CONCLUSION: CDED plus PEN was better tolerated than EEN in

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and play a crucial role in maintaining epidermal integrity and barrier function. SAM syndrome-causing mutations resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. The deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

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Thirty children suffering from different types of malignancies, neutropenic fever, and suspected staphylococcal bacteremia were evaluated for the pharmacokinetics of vancomycin in steady-state conditions and compared with eight children suffering from proven methicillin-resistant staphylococcal infection. All the studied population received intravenous vancomycin at 40 mg/kg daily divided into four daily doses. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood vancomycin samples. The mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax (microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours; 0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8) and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the malignancy and control groups, respectively. The malignancy group had a significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower Cmin (P = .03) in comparison with the control group. It is suggested that the prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is safe and will provide a peak blood level of vancomycin sufficient to cover the broad spectrum of staphylococcal bacteria. The vancomycin dose should be individualized, based on an individual pharmacokinetic profile.