Hideaki Matsuura

BACKGROUND AND OBJECTIVES: Reports on the changes in plasma fibrinogen levels in patients receiving cryoprecipitates synthesized using different methods are lacking. Therefore, we investigated these changes in patients who underwent cardiovascular surgery. MATERIALS AND METHODS: We included 309 patients who underwent cardiovascular surgery and received 12 cryoprecipitate units between February 2020 and March 2024 and 204 patients were selected by propensity score matching. The cryoprecipitates were prepared using two methods. Fresh frozen plasma (FFP) was thawed at 2 to 6°C for 24 h and centrifuged to remove the supernatant in the one-step method, whereas FFP was thawed, refrozen at -20°C, and subsequently rethawed in the two-step method. We investigated the association between different cryoprecipitate preparation methods and ICU admission for ≥ 1 week, with in-hospital mortality considered as a competing risk in the analysis. In addition, we evaluated the changes in plasma fibrinogen levels before and after cryoprecipitate administration. RESULTS: Baseline plasma fibrinogen levels were significantly higher in the two-step method group than in the one-step method group. Differences in cryoprecipitate preparation methods were not significantly associated with ICU admission for ≥ 1 week, in the analysis that considered in-hospital mortality as a competing risk (P = 0.93). The increase in plasma fibrinogen levels after cryoprecipitate administration was significantly higher with the two-step method than with the one-step method (36 mg/dL vs. 51 mg/dL, P = 0.020). CONCLUSION: The cryoprecipitates synthesized using the two-step method showed a higher increase in plasma fibrinogen levels than those prepared using the one-step method. These findings may help guide appropriate transfusion protocols by confirming intraoperative plasma fibrinogen levels.

This study investigated the anti-tumor effects of andrographolide, a diterpene lactone derived from Andrographis paniculata, on T-cell acute lymphoblastic leukemia (T-ALL) cells. Andrographolide induced dose-dependent cytotoxicity and morphological changes in the T-ALL cell line Jurkat cells, including cell shrinkage and chromatin condensation. Mechanistically, andrographolide triggers apoptosis through reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, and cytochrome c release. These effects were reversed by the ROS inhibitor N-acetyl-L-cysteine (NAC), indicating that andrographolide induces apoptosis through a ROS-dependent apoptotic pathway. In contrast, NAC treatment did not reverse cytarabine- and vincristine-induced apoptosis or the ROS-dependent apoptotic pathway in Jurkat cells. Intriguingly, andrographolide also induced ferroptosis, as evidenced by increased expression of the ferroptosis marker fatty acid-CoA ligase 4 and ultrastructural changes such as reduced mitochondrial area and disappearance of cristae. These effects were likewise reversed by NAC, further implicating ROS in the ferroptotic process. In MOLT-4 cells, where andrographolide suppressed viability, increased Annexin V positivity and ROS levels, and upregulated FACL4 expression in a NAC-sensitive manner. Unlike cytarabine and vincristine, andrographolide did not significantly alter cell cycle distribution. In conclusion, andrographolide induces both apoptosis and ferroptosis in T-ALL cells via ROS-dependent mechanisms that are distinct from those of conventional chemotherapeutic agents. These dual actions position andrographolide as a candidate for standalone or combination therapy in T-ALL.