Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods: Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results: Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSCassociated neuropsychiatric disorders, and new medication approvals. Conclusions: Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.

Background: The aim of the study was to investigate the effects of probiotics on moderate or severe atopic dermatitis (AD) in young children. Methods: Fifty six children aged 6-18 months with moderate or severe AD were recruited into a randomised double blind placebo controlled trial in Perth, Western Australia; 53 children completed the study. The children were given a probiotic (1610 9 Lactobacillus fermentum VRI-033 PCC; Probiomics) or an equivalent volume of placebo, twice daily for 8 weeks. A final assessment at 16 weeks was performed. Results: The main outcome measures were severity and extent of AD at the end of the study, as measured by the Severity Scoring of Atopic Dermatitis (SCORAD) index. The reduction in the SCORAD index over time was significant in the probiotic group (p = 0.03) but not the placebo group. Significantly more children receiving probiotics (n = 24, 92%) had a SCORAD index that was better than baseline at week 16 compared with the placebo group (n = 17, 63%) (p = 0.01). At the completion of the study more children in the probiotic group had mild AD (n = 14, 54%) compared to the placebo group (n = 8, 30%). Conclusion: Supplementation with probiotic L fermentum VRI-003 PCC is beneficial in improving the extent and severity of AD in young children with moderate or severe disease.

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.

Microcephaly-capillary malformation (MIC-CAP) syndrome exhibits severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We employed whole-exome sequencing of five patients with MIC-CAP syndrome and identified novel recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein)/AMSH (Associated Molecule with the SH3 domain of STAM), that plays a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways. The latter cellular phenotype is significant considering the established connection between these pathways and their association with vascular and capillary malformations. Furthermore, our findings of a congenital human disorder caused by a defective DUB protein that functions in endocytosis, implicates ubiquitin-conjugate aggregation and elevated apoptosis as factors potentially influencing the progressive neuronal loss underlying MIC-CAP.

To determine the effect of bacterial colonization on venous ulcer healing, 82 patients with 100 venous ulcerated limbs were each studied prospectively for six months. Despite bacteriological swab results, topical or systemic antibiotics were not administered unless cellulitis supervened. Initial ulcer size, length of ulcer history and time to complete healing of colonized and uncolonized ulcers were determined and compared. Organisms were cultured from 83 limbs prior to commencement of treatment, the commonest isolates being Staphylococcus aureaus (48%), mixed coliforms (28%), Pseudomonas aeruginosa (21%) and anaerobes (17%). When compared with ulcers with no bacterial growth, colonized ulcers were of longer duration (p [symbol: see text] 0.01), had a larger initial size (p [symbol: see text] 0.001) and had significantly longer healing time (p [symbol: see text] 0.001). When analysed individually beta-haemolytic streptococci, anaerobes, Staphylococcus aureus and coliforms were associated with delayed healing. Delayed healing was not found with Pseudomonas aeruginosa, although pseudomonas-colonized ulcers were significantly larger and of longer duration than uncolonized ulcers. Bacterial colonization is associated with delayed venous ulcer healing. To further clarify the pathogenicity of colonizing bacteria, however, the effect of their eradiction on healing of venous ulcers needs to be established.