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IMPORTANCE: Mitotane (Lysodren, o,p'-DDD [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane)] is currently the only United States Food and Drug Administration and European Medicines Agency-approved product for the treatment of adrenocortical carcinoma. OBSERVATIONS: Mitotane is challenging to administer; however, its toxicities (specifically adrenal insufficiency) are well known, and the management of adverse consequences has established approaches. While often viewed through the prism of a cytotoxic agent, it can also interfere with hormone production making it a valuable asset in managing functional ACC. A recently completed prospective trial has shed some light on its use in the adjuvant setting, but further clarity is needed. Many think mitotane has a role in the advanced or metastatic setting, although prospective data are lacking and retrospective analyses are often difficult to interpret. CONCLUSIONS AND RELEVANCE: When used carefully and thoughtfully, especially in patients with hormonal excess, mitotane is an important component of the treatment armamentarium for ACC.
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Climate change undeniably impacts the social and environmental determinants of one's health. The healthcare sector, encompassing medications and the pharmaceutical industry supply chain, accounts for a significant portion of global health care contributions to greenhouse gas (GHG) and waste production. Despite these realities, healthcare professionals - physicians, pharmacists, nurses, and others - may be unaware of GHG emissions and the long-term environmental effects of the medications they prescribe, dispense, and administer daily. In this commentary, we identify existing challenges and explore potential strategies to recognize and reduce the climate change impacts associated with medication use.
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Efecto Invernadero , Gases de Efecto Invernadero , Humanos , Gases de Efecto Invernadero/análisis , Salud GlobalRESUMEN
The most common adverse event associated with chimeric antigen receptor T-cell therapy is cytokine release syndrome, which is characterized by fever, hypoxia, and hypotension in varying degrees of severity. In severe cases, cytokine release syndrome can result in life-threatening symptoms such as multi-organ failure. The widely accepted first-line therapy for cytokine release syndrome management is tocilizumab with or without corticosteroids, but there is very limited guidance on the proper management of patients unresponsive to this regimen. There are emerging strategies that target cytokine release syndrome through novel mechanisms, showing promise in treating or preventing severe cytokine release syndrome. Although further clinical investigation is necessary to assess the applicability of the emerging approaches, these exploratory therapies may shape the future landscape of chimeric antigen receptor T-cell induced cytokine release syndrome management. This review article provides a comprehensive overview of the current and emerging therapies for the management of chimeric antigen receptor T-cell induced cytokine release syndrome, especially cases that are refractory to tocilizumab and steroids.