Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.
The first isolation and structure identifications of prednisone and prednisolone were done in 1950 by Arthur Nobile .    The first commercially feasible synthesis of prednisone was carried out in 1955 in the laboratories of Schering Corporation, which later became Schering-Plough Corporation , by Arthur Nobile and coworkers.  They discovered that cortisone could be microbiologically oxidized to prednisone by the bacterium Corynebacterium simplex. The same process was used to prepare prednisolone from hydrocortisone . 
Great study. While disappointing not to have a mortality benefit, the secondary outcomes are of clinical significance and are likely to increase the use of hydrocortisone in our ICU. At the moment we use bolus dosing, which has been shownpreviously to be non-inferior to continuous infusions, but with more hyperglycaemia and less need for additional lines (Hoang H, Wang S, Islam S, Hanna A, Axelrad A, Brathwaite C. Evaluation of hydrocortisone continuous infusion versus intermittent boluses in resolution of septic shock. P T. 2017; 42 (4): 252-255.). We tend to initiate hydrocortisone once noradrenaline infusion rate goes beyond 10mcg/min and we have variation in practice in terms of tapering or stopping hydrocortisone once vasopressor support is off. The timing of hydrocortisone initiation would be an interesting future study to guide practice.