ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Bone Miner Res 2018;33(7):1260-1271Osteogenesis imperfecta (OI) is characterized by early-onset skeletal fragility, often short stature, blue sclerae and some other features. OI is caused by mutations in the two genes encoding type I collagen, namely COL1A1 and COL1A2. Some previous reports have indicated that when the mutation involves the C-propeptide cleavage site in e...

To read the full abstract: N Engl J Med. 2018; 378(9): 797-808Sepsis has been identified by the WHO as a global health priority, however, there has been no proven pharmacologic treatment other than the appropriate antibiotic agents, fluids and vasopressors as required. Reported death rates among hospitalized patients with sepsis range between 30-45% (22). Glucocorticoids have been used as ...

To read the full abstract: Lancet 2017;390:1664-1675Whoever could have imagined that a compound discovered as being secreted by enteroendocrine cells in the gut could have a role in treating Parkinson’s disease? GLP-1 does indeed have diverse actions on several peripheral organs (including tongue, stomach, adipose tissues, muscle, pancreas and liver) and on the brainstem to regulate...

In Brief: This phase 2 study investigated the effect of the RANKL inhibitor denosumab on fibrous dysplasia lesion activity, as well as the rebound in bone turnover after treatment discontinuation.Commentary: Denosumab is a humanized monoclonal antibody that inhibits RANKL with potent but transient antiosteoclastic effects, and discontinuation of denosumab treatment is associated with a rebound in bone turnover. In this study, eight women received high do...

In Brief: These authors studied liver-specific SIRT2 knockout mice to examine how loss of hepatocyte SIRT2 (Sirtuin 2) prevents bone loss in aged mice. Hepatocyte SIRT2 deficiency led to upregulation of Leucine rich α2 glycoprotein (LRG1) in hepatocyte-derived small extracellular vesicles (sEVs) which inhibited osteoclastogenesis in bone marrow.Commentary: Liver-bone communication has been implicated in bone homeostasis. P...

Brief summary: In this experimental study, pancreas-derived mesenchymal stem cells (PMSCs) were implanted into the kidney capsule of mice with streptozotocin (STZ)-induced diabetes. PMSCs led to increased levels of IL-6 in T-helper 1 and T-helper 17 cells, which transiently activated tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), which in turn decreased levels of interleukin-17. This was associated with exocrine pancreas regeneration and rescue of ...

Brief summary: In this experimental study, immunomodulatory microparticles, consisting of encapsulating self-antigens with rapamycin, were injected into mouse lymph nodes to protect against type 1 diabetes (T1D) and islet graft rejection. Antigens and rapamycin were both required for maximal efficacy and they induced durable tolerance, accompanied by expansion of antigen-specific regulatory T cells (Treg) in both treated and untreated lymph nodes.Antigen...

Brief summary: The Human Pangenome Reference Consortium reports a first draft of the human pangenome reference due to replace the existing reference GRCh38 (1, 2). It is an updated, high-quality, graph-based, telomere-to-telomere representation of global genomic diversity including common variants (single-nucleotide variants, structural variants and functional elements).The human reference genome is the fundamental, open-access resource of modern human g...

Brief summary: This observational study in three different cohorts found an increased risk for atherothrombotic disease associated with the commonly used sugar substitute erythritol. Untargeted metabolomics (in cohort 1, n=1157) and targeted metabolomics (in cohorts 2 and 3, n=2149 USA and n=833 Europe, respectively) investigations revealed an increased risk for major adverse cardiovascular events (MACE) including death, myocardial infarction and str...

To read the full abstract: Nature. 2018 Jul;559(7714):405–409This article decries a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences at specific sites in the genomes of primary human T cells, while preserving cell viability and function.The common approach to genetically...