Journal of internal medicine
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Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. ⋯ Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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Dyspnea is common after COVID-19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea. ⋯ DCE-MRI demonstrated late contrast bolus arrival in males with post-COVID dyspnea, suggestive of primary vascular lesions or secondary effects of hypoxic vasoconstriction. Since this effect was not regularly observed in female patients, our findings suggest sex differences in the mechanisms underlying post-COVID dyspnea, which warrants further investigation in dedicated trials.
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Graves' orbitopathy (GO) is an orbital autoimmune disorder and the main extrathyroidal manifestation of Graves' disease, the most common cause of hyperthyroidism. GO affects about 30% of Graves' patients, although fewer than 10% have severe forms requiring immunosuppressive treatments. Management of GO requires a multidisciplinary approach. ⋯ Recent studies suggest a secular trend toward a milder phenotype of GO. Standardized assessment at a thyroid eye clinic allows for a better general management plan. Treatment of active moderate-to-severe forms of GO still relies in most cases on high-dose systemic-mainly intravenous-glucocorticoids as monotherapy or in combination with other therapies-such as mycophenolate, cyclosporine, azathioprine, or orbital radiotherapy-but novel biological agents-including teprotumumab, rituximab, and tocilizumab-have achieved encouraging results.
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Numerous studies have shown that epigenetic age-an individual's degree of aging based on patterns of DNA methylation-can be computed and is associated with an array of factors including diet, lifestyle, genetics, and disease. One can expect that still further associations will emerge with additional aging research, but to what end? Prediction of age was an important first step, but-in our view-the focus must shift from chasing increasingly accurate age computations to understanding the links between the epigenome and the mechanisms and physiological changes of aging. ⋯ Second, we discuss research that exemplifies how investigation of the epigenome is building a mechanistic theory of aging and informing clinical practice. Such examples include identifying methylation sites and the genes most strongly predictive of aging-a subset of which have shown strong potential as biomarkers of neurodegenerative disease and cancer; relating epigenetic clock predictions to hallmarks of aging; and using longitudinal studies of DNA methylation to characterize human disease, resulting in the discovery of epigenetic indications of type 1 diabetes and the propensity for psychotic experiences.