Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse.

Background Tracheostomy is one of the most common surgical procedures performed on ventilated COVID-19 patients yet the appropriate timing for operating is controversial. Objectives Assessing the effect of early tracheostomy on mortality and decannulation; elucidating changes in ventilation parameters, vasopressors and sedatives dosages immediately following the procedure. Methods A retrospective cohort of 38 ventilated COVID-19 patients, 19 of them (50%) underwent tracheostomy within 7 days of intubation (early tracheostomy group) and the rest underwent tracheostomy after 8 days or more (late tracheostomy group). Results Decannulation rates were significantly higher while mortality rates were non-significantly lower in the early tracheostomy group compared with the late tracheostomy group (58% vs 21% p < 0.05; 42% vs 74% p = 0.1, respectively). Tidal volume increased (446 ml vs 483 ml; p = 0.02) while PEEP (13 cmH 2 0 vs 11.6 cmH 2 O, p = 0.04) decreased at the immediate time following the procedure. No staff member participating in the procedures was infected with SARS-CoV-2 virus. Conclusion Early tracheostomy might offer improved outcomes with higher decannulation rates and lower mortality rates in ventilated COVID-19 patients, yet larger scale studies are needed. Most likely, early exposure to COVID-19 patients with appropriate personal protective equipment during open tracheostomy does not put the surgical team at risk.

No abstract