Gut microbial dysbiosis in patients with Cushing's disease in long-term remission. Relationship with cardiometabolic risk.

Background: Patients with Cushing's disease (CD) in remission maintain an increased cardiovascular risk. Impaired characteristics of gut microbiome (dysbiosis) have been associated with several cardiometabolic risk factors. Methods: Twenty-eight female non-diabetic patients with CD in remission with a mean ± SD) age of 51 ± 9 years, mean ( ± SD) BMI, 26 ± 4, median (IQR) duration of remission, 11(4) years and 24 gender-, age, BMI-matched controls were included. The V4 region of the bacterial 16S rDNA was PCR amplified and sequenced to analyse microbial alpha diversity (Chao 1 index, observed number of species, Shannon index) and beta diversity analysis through the Principal Coordinates Analysis (PCoA) of weighted and unweighted UniFrac distances. Inter-group difference in microbiome composition was analysed using MaAsLin2. Results: The Chao 1 index was lower in CD as compared with controls (Kruskal-Wallis test, q = 0.002), indicating lower microbial richness in the former. Beta diversity analysis showed that faecal samples from CS patients clustered together and separated from the controls (Adonis test, p<0.05). Collinsella, a genus form of the Actinobacteria phylum was present in CD patients only, whereas Sutterella, a genus from Proteobacteria phylum, was scarcely detectable/undetectable in CD patients as well as Lachnospira, a genus of the Lachnospiraceae family of the Firmicutes phylum. In CS, the Chao 1 index was associated with fibrinogen levels and inversely correlated with both triglyceride concentrations and the HOMA-IR index (p<0.05). Conclusions: Patients with CS in remission have gut microbial dysbiosis which may be one of the mechanisms whereby cardiometabolic dysfunctions persist after "cure".

[The need of circumcision or prepuce dilation. A study with 1200 boys]. / Necesidad de circuncisión o dilatación del prepucio. Estudio de 1.200 niños.

OBJECTIVES: To demonstrate the increase of preputial retractability with age. To point out the small usefulness of circumcision and preputial forced dilation during childhood. METHODS: The development of the prepuce and its retractability were evaluated in 1200 boys between 0 and 16 years. The prepuce was classified as type I to V depending on its lower or higher retractability in all cases having been dilated previously or not. RESULTS: Prepuce retractability in boys under one year was type I (not retractile) in 63.4%, whereas it was type V (completely retractile) in only 3.7%. The contrary was observed in adolescents (11 to 16 years), in which type I was 0.9% and type V was observed in 80.9%. It was also observed that 309 boys (43. 1%) among the 717 with previous prepuce forced dilation, had types I to IV prepuces, so, they had acquired new balanopreputial adherences by the time of examination for our study. Seventeen boys (0.4%) required circumcision. No children suffered upper urinary tract infections. CONCLUSIONS: All boys are born with the prepuce covering the glans penis, keeping adherences between both structures, which disappear with age, being the detachment complete at the time of puberty in most boys. So, we consider circumcision or forced dilation of the prepuce unnecessary in most boys.