No abstract

BackgroundShunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively. Several mechanisms may be responsible, one of which involves shunt infiltration by reactive cells from the brain parenchyma. This has not been modeled in culture and cannot be consistently examined in vivo without a large sample size.MethodsWe have developed and tested a three-dimensional in vitro model of astrocyte migration and proliferation around clinical grade ventricular catheters and into catheter holes that mimics the development of cellular outgrowth from the parenchyma that may contribute to shunt obstruction.ResultsCell attachment and growth was observed on shunt catheters for as long as 80 days with at least 77 % viability until 51 days. The model can be used to study cellular attachment to ventricular catheters under both static and pulsatile flow conditions, which better mimic physiological cerebrospinal fluid dynamics and shunt system flow rates (0.25 mL/min, 100 pulses/min). Pulsatile flow through the ventricular catheter decreased cell attachment/growth by 63 % after 18 h. Under both conditions it was possible to observe cells accumulating around and in shunt catheter holes.ConclusionsAlone or in combination with previously-published culture models of shunt obstruction, this model serves as a relevant test bed to analyze mechanisms of shunt failure and to test catheter modifications that will prevent cell attachment and growth.

With improved therapies, people with cystic fibrosis are living longer and healthier lives and increasingly have questions surrounding their sexual and reproductive health. This article will summarize the important issues of which providers should be aware during the lifespan of people with cystic fibrosis, including puberty, adulthood, and menopause.A wide range of sexual and reproductive health topics are addressed such as puberty, transgender and gender nonbinary identities, contraception, sexually transmitted infections, hypogonadism, sexual functioning, cyclical hemoptysis, and urinary incontinence. We discuss gaps in knowledge and current evidence as well as management strategies to optimize care. Our goal is to support providers to enable them to give comprehensive care throughout the lifespan of people with cystic fibrosis.

As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies. To this end, we must identify areas for which harmonization is lacking and for which efficiencies can be gained to promote ethical, feasible, and credible study designs amidst the changing CF care landscape. This article summarizes the counsel from core advisors across multiple international regions and clinical trial networks, developed during a one-day workshop in October 2019. The goal of the workshop was to identify, in consideration of the highly transitional era of CFTR modulator availability, the drug development areas for which global alignment is currently uncertain, and paths forward that will enable advancement of CF therapeutic development.