The antioxidant or pro-oxidant actions and their involvement in the epigenome regulation by the phytochemical phenolic antioxidants should be at least established in the cellular models under normal and pathophysiological states. The current review discusses the mechanisms of modulation of the mammalian cellular epigenome by the phytochemical phenolic antioxidants with implications in human diseases.

BACKGROUND: Using a large national database, we evaluated the relationship between RBC transfusion volume, RBC transfusion rate, and in-hospital mortality to explore the presence of a futility threshold in trauma patients receiving ultramassive blood transfusion. STUDY DESIGN: The ACS-TQIP 2013 to 2018 database was analyzed. Adult patients who received ultramassive blood transfusion (≥20 units of RBC/24 hours) were included. RBC transfusion volume and rate were captured at the only 2 time points available in TQIP (4 hours and 24 hours), or time of death, whichever came first. RESULTS: Among 5,135 patients analyzed, in-hospital mortality rate was 62.1% (n = 3,190), and 4-hour and 24-hour mortality rates were 17.53% (n = 900) and 42.41% (n = 2,178), respectively. RBC transfusion volumes at 4 hours (area under the receiver operating characteristic curve [AUROC] 0.59 [95% CI 0.57 to 0.60]) and 24 hours (AUROC 0.59 [95% CI 0.57 to 0.60]) had low discriminatory ability for mortality and were inconclusive for futility. Mean RBC transfusion rates calculated within 4 hours (AUROC 0.65 [95% CI 0.63 to 0.66]) and 24 hours (AUROC 0.85 [95% CI 0.84 to 0.86]) had higher discriminatory ability than RBC transfusion volume. A futility threshold was not found for the mean RBC transfusion rate calculated within 4 hours. All patients with a final mean RBC transfusion rate of ≥7 U/h calculated within 24 hours of arrival experienced in-hospital death (n = 1,326); the observed maximum length of survival for these patients during the first 24 hours ranged from 24 hours for a rate of 7 U/h to 4.5 hours for rates ≥21 U/h. CONCLUSION: RBC transfusion volume within 4 or 24 hours and mean RBC transfusion rate within 4 hours were not markers of futility. The observed maximum length of survival per mean RBC transfusion rate could inform resuscitation efforts in trauma patients receiving ongoing transfusion between 4 and 24 hours.