Highlights d TCR signaling and CD8 + T effector program are altered by the absence of CD226 d Dysfunctional CD226 neg CD8 + TILs accumulate in human and mouse tumors d Eomes overexpression is involved in CD226 loss by CD8 + TILs d CD226 loss limits the efficacy of immune checkpoint blockade and CD137 agonists.
In contrast to the product information, we recommend giving the full dose of caspofungin regardless of the presence and severity of cirrhosis to avoid a subtherapeutic exposure.
Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.
A young woman presented with initial epileptic seizures and multiple ‘mass-like’ lesions seen on computed tomography and magnetic resonance imaging. Given this presentation and her past medical history, a cerebral biopsy was performed to rule out malignancy, but showed a necrotizing cerebral vasculitis. We describe this case to reinforce the view that primary central nervous system vasculitis (PCNSV) should be considered in the differential diagnosis of a cerebral mass, even if uncommon.LEARNING POINTSPCNSV may cause a variety of clinical manifestations including seizures.PCNSV lesions can mimic a cerebral mass.Brain biopsy remains the gold standard for the diagnosis of PCNSV, especially to rule out a cancer diagnosis.
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