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Abstract Although human cultures stimulated with dexamethasone suggest that the glucocorticoid receptor (GR) activates stress erythropoiesis, the effects of GR activation on erythropoiesis in vivo remains poorly understood. We characterized the phenotype of a large cohort of patients with Cushing’s Disease, a rare condition associated with elevated cortisol levels. Results from hypercortisolemic patients with active Cushing’s were compared with those obtained from eucortisolemic patients after remission and from non-diseased volunteers. Active Cushing’s patients exhibit erythrocytosis associated with normal hemoglobin F levels. In addition, their blood contained elevated numbers of the GR-induced CD163+ monocytes and a unique class of CD34+ cells expressing CD110, CD36, CD133 and the GR-target gene CXCR4. When cultured, these CD34+ cells generated similarly large numbers of immature erythroid cells in the presence and absence of dexamethasone, with raised expression of the GR-target gene GILZ. Of interest, blood from Cushing’s patients in remission maintained high numbers of CD163+ monocytes and, although their CD34+ cells had a normal phenotype, these cells were unresponsive to added dexamethasone. Collectively, these results indicate that chronic exposure to excess glucocorticoids in vivo leads to erythrocytosis by generating erythroid progenitor cells with a constitutively active GR. Although remission rescues the erythrocytosis and the phenotype of the circulating CD34+ cells, a memory of other prior changes is maintained in remission. From https://haematologica.org/article/view/haematol.2021.280542
Dexamethasone, a cheap and widely used steroid, has become the first drug shown to be able to save lives among Covid-19 patients in what scientists hailed as a “major breakthrough”. Results of trials announced on Tuesday showed dexamethasone, which is used to reduce inflammation in other diseases, reduced death rates by around a third among the most severely ill Covid-19 patients admitted to hospital. The results suggest the drug should immediately become standard care in patients with severe cases of the pandemic disease, said the researchers who led the trials. “This is a result that shows that if patients who have Covid-19 and are on ventilators or are on oxygen are given dexamethasone, it will save lives, and it will do so at a remarkably low cost,” said Martin Landray, an Oxford University professor co-leading the trial, known as the RECOVERY trial. “It’s going to be very hard for any drug really to replace this, given that for less than 50 pounds ($63.26), you can treat eight patients and save a life,” he told reporters in an online briefing. His co-lead investigator, Peter Horby, said dexamethasone was “the only drug that’s so far shown to reduce mortality - and it reduces it significantly.” “It is a major breakthrough,” he said. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.” There are currently no approved treatments or vaccines for Covid-19, the disease caused by the new coronavirus which has killed more than 431,000 globally. Saving ‘countless lives’ The RECOVERY trial compared outcomes of around 2,100 patients who were randomly assigned to get the steroid, with those of around 4,300 patients who did not get it. The results suggest that one death would be prevented by treatment with dexamethasone among every eight ventilated Covid-19 patients, Landray said, and one death would be prevented among every 25 Covid-19 patients that received the drug and are on oxygen. Among patients with Covid-19 who did not require respiratory support, there was no benefit from treatment with dexamethasone. “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients,” Horby said. Nick Cammack, a expert on Covid-19 at the Wellcome Trust global health charity, said the findings would “transform the impact of the Covid-19 pandemic on lives and economies across the world”. “Countless lives will be saved globally,” he said in a statement responding to the results. The RECOVERY trial was launched in April as a randomised clinical trial to test a range of potential treatments for Covid-19, including low-dose dexamethasone and the malaria drug hydoxycholoroquine. The hydroxychloroquine arm was halted earlier this month after Horby and Landray said results showed it was “useless” at treating Covid-19 patients. Global cases of infection with the novel coronavirus have reached over 8 million, according to a Reuters tally, and more than 434,000 people have died after contracting the virus, the first case if which was reported in China in early January. From https://www.cnbc.com/2020/06/16/steroid-dexamethasone-reduces-deaths-from-severe-covid-19-trial.html