Development of a Tool to Guide Parents Carrying a BRCA1/2 Mutation Share Genetic Results with Underage Children.

Although most parents carrying a BRCA1/2 genetic mutation share their test result with their underage children, they report needing support to decide if, when, and how to share risk information and what reactions to expect from their children. We developed a tool to guide parents carrying a BRCA1/2 mutation share their genetic result with underage children. Here, we report on the development of this tool using a qualitative methodology. A tool prototype was developed based on the International Patient Decision Aids Standards Collaboration framework. Content was assessed using feedback from focus groups, individual interviews, and a 12-item reading grid. Participants were nine BRCA1/2 mutation carriers with underage children and three cancer genetics health professionals. Thematic content analysis was conducted on interview transcripts. The tool was developed using an iterative process until saturation of data. An independent advisory committee was involved in all steps of tool development until reaching consensus. Rather than a decision aid per se (to communicate or not), the parents wanted a more comprehensive tool to help them communicate genetic test result to their children. To meet parents' needs, a communication guidance booklet was developed, setting out the pros and cons of communication, steps to prepare sharing the test result, communication tips, and parents' testimonies. This communication tool responds to a significant unmet need faced by parents carrying a genetic predisposition to cancer. Future studies are needed to assess how the information from the parent's genetic test result impacts the child's development, health behaviors, and relationship with the parent.

POEMS Syndrome Complicated by Extensive Calciphylaxis: A Remarkable Recovery.

BACKGROUND AND OBJECTIVE: Calciphylaxis is life threatening. It has traditionally been associated with end-stage renal disease and hyperparathyroidism but is increasingly common in other clinical contexts. The association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and calciphylaxis has been reported only in a few cases. This case is the first of patient survival in such widespread disease. METHODS AND RESULTS: A 42-year-old man with POEMS syndrome developed extensive calciphylaxis despite normal renal and parathyroid function. Rapid diagnosis, treatment, and supportive care contributed to full clinical resolution. CONCLUSION: This is the fifth case of POEMS syndrome associated with calciphylaxis. The observations from this report suggest that POEMS syndrome might be an independent risk factor for the development of calciphylaxis. This case underlines the importance of careful follow-up in patients with POEMS syndrome and prompt diagnosis and treatment of associated calciphylaxis.

Platelet-activating factor induces Th17 cell differentiation.

Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1ß expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.