Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

SUMMARY AimTo review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children. MethodsThe following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and LGG: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included. ResultsEight RCTs (988 participants) met the inclusion criteria. Compared with controls, LGG had no effect on the total stool volume (two RCTs, n = 303). However, LGG was associated with a significant reduction in diarrhoea duration (seven RCTs, 876 infants, weighted mean difference, WMD )1.1 days (95% confidence interval, CI )1.9 to )0.3), particularly of rotavirus etiology (WMD )2.1 days, 95% CI )3.6 to )0.6), risk of diarrhoea >7 days (one RCT, n = 287, relative risk 0.25, 95% CI 0.09-0.75) and duration of hospitalization (three RCTs, n = 535, WMD )0.58, 95% CI )0.8 to )0.4; significance was lost in the random effect model). There was no reduction in the number of stools at any time interval. ConclusionsThe use of LGG is associated with moderate clinical benefits in the treatment of acute diarrhoea in children. These findings should be interpreted with caution due to the important methodological limitations and heterogeneity of most of the studies.

SUMMARY BackgroundThe efficacy of each probiotic should be evaluated separately. Previously, we have shown that Lactobacillus GG (LGG) is effective in treating acute gastroenteritis (AGE) in children.

SUMMARY BackgroundSaccharomyces boulardii is a non-pathogenic probiotic yeast considered useful against enteropathogens.

We replicated the association between Graves' disease and PTPN22 'T' reported in British Caucasians. We also found a gene dose-dependent effect of PTPN22 'T' on the age of onset of Graves' disease.

Despite research the role of the M34T and V37I variants of GJB2 in causing hearing impairment (HI) remains controversial. Our purpose was to test a hypothesis that M34T and V37I are pathogenic but have distinct features resulting in a reduced penetrance. We screened for known GJB2/GJB6 mutations 233 Polish consecutive unrelated subjects with non-syndromic, sensorineural HI who were previously found to carry 35delG mutation on one chromosome. The most frequent mutations were also analyzed in approximately 1,000 controls. We found that M34T and V37I were significantly (P << 10(-6)) overrepresented among patients, but their penetrance was estimated as 1/10 relative to mutations of undisputed pathogenicity. This finding apparently could not be explained by low degree of HI associated with M34T and V37I since another mutation causing comparably mild HI (L90P) did not have reduced penetrance. Subsequent analyses showed that the patients with M34T/35delG and V37I/35delG had significantly later onset of HI than patients with other genotypes (P < 10(-6)) including the L90P/35delG (P = 0.006). Also, among these patients (but not others) a strong correlation between the degree of HI and its duration was found (r = 0.79, P < 10(-5)). We tentatively suggest that M34T and V37I might cause mild HI characterized by relatively late onset and progression.

Background:Recently, evidence from a large randomised controlled trial (RCT) negated efficacy of Lactobacillus rhamnosus GG for treating acute gastroenteritis in children.Aim: To review RCTs in which L rhamnosus GG was used to treat acute gastroenteritis in children. Methods:The Cochrane Library, MEDLINE, and EMBASE databases were searched from May 2013 (end of last search) to January 2019. The primary outcomes were stool volume and duration of diarrhoea.Results: Eighteen RCTs (n = 4208) were included. Compared with placebo or no treatment, L rhamnosus GG use had no effect on stool volume but was associated with a reduced duration of diarrhoea (15 RCTs, n = 3820, mean difference, MD −0.85 day, 95% CI −1.15 to −0.56). L rhamnosus GG was effective when used at a daily dose of ≥10 10 CFU or <10 10 CFU; however, the latter produced results of borderline significance. L rhamnosus GG was more effective when used in European countries compared with non-European countries, particularly when considered by region.L rhamnosus GG use was associated with a reduced duration of hospitalisation. One RCT found that L rhamnosus GG had no effect on the total clinical severity score at 14 days after enrolment. Conclusions:Despite a recent large RCT demonstrating no effect of L rhamnosus GG, current evidence shows that, overall, L rhamnosus GG reduced both the duration of diarrhoea (with a higher impact in European countries) and hospitalisation in inpatients. These findings should be viewed in the context of the high heterogeneity and methodological limitations of the included trials. | 1377SZAJEWSKA Et Al.

SummaryNon-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, some of which are structurally identical or similar to those found in human milk. In a controlled, randomized doubleblinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milkderived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'-and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacteriumdominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum).