Immunomodulatory drugs for COVID-19 (one or more per patient) included corticosteroids (7), interleukin-7 (8), and tocilizumab (1). Continuous variables are expressed as median (interquartile range), and categorical variables as n and (%).
AMP-activated protein kinase (AMPK) α1 is activated in platelets on thrombin or collagen stimulation, and as a consequence, phosphorylates and inhibits acetyl-CoA carboxylase (ACC). Because ACC is crucial for the synthesis of fatty acids, which are essential for platelet activation, we hypothesized that this enzyme plays a central regulatory role in platelet function. To investigate this, we used a double knock-in (DKI) mouse model in which the AMPK phosphorylation sites Ser79 on ACC1 and Ser212 on ACC2 were mutated to prevent AMPK signaling to ACC. Suppression of ACC phosphorylation promoted injury-induced arterial thrombosis in vivo and enhanced thrombus growth ex vivo on collagen-coated surfaces under flow. After collagen stimulation, loss of AMPK-ACC signaling was associated with amplified thromboxane generation and dense granule secretion. ACC DKI platelets had increased arachidonic acid-containing phosphatidylethanolamine plasmalogen lipids. In conclusion, AMPK-ACC signaling is coupled to the control of thrombosis by specifically modulating thromboxane and granule release in response to collagen. It appears to achieve this by increasing platelet phospholipid content required for the generation of arachidonic acid, a key mediator of platelet activation.
Aims: We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunoglobulins (TSI) in patients with Graves’ disease. Methods: We retrospectively studied 80 patients initially treated with antithyroid drugs and requiring either RAI (8.3 ± 1.7 mCi of 131I; n = 40) or TTx (n = 40) as second-line therapy. Results: The TTx and RAI groups were not different, except for larger goiter, higher FT3 and more frequent Graves’ orbitopathy at diagnosis in the surgery group (p < 0.05). A persistent remission of hyperthyroidism was observed in 97% of operated patients versus 73% of the RAI patients at 3 years (p < 0.01). TTx was followed by a rapid and steady decrease in TSI during the first 9 months, while a surge of antibodies was observed during the first 6 months after RAI, followed by a slow decrease over the next 18 months. At the last visit, high TSI levels were still observed in 18 and 60% of patients in the surgery and RAI groups, respectively (p < 0.001). Conclusions: TTx is more efficient than RAI to induce a rapid and permanent correction of hyperthyroidism and TSI decrease in patients previously treated with antithyroid drugs.
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