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There are reports of rare cases of toxicity following dosing within the therapeutic range, although there is debate about whether this latter category truly exists

It is known that a widespread characteristic of tumors is their inability to develop adequate blood vessels with the consequence being relative hypoxia: at moderate levels, ROS induce transcription of HIF1, the founding member of the family of hypoxia-induced factors, and stabilize the encoded protein, which is normally hydroxylated within less than 5 min, by inhibiting the activity of the iron-dependent prolyl 4-hydroxylase (PHD) involved in its degradation 29

(4) FY 2022 Outlier Payments Our current estimate, using available FY 2022 claims data, is that actual outlier payments for FY 2022 were approximately 6.73 percent of actual total MS-DRG payments

Sharma RK, Agarwal A