The potential use of game theory in decision-making in CHD.

Background: Congenital cardiac care involves multiple stakeholders including patients and their families, surgeons, cardiologists, anaesthetists, the wider multidisciplinary team, healthcare providers, and manufacturers, all of whom are involved in the decision-making process to some degree. Game theory utilises human behaviour to address the dynamics involved in a decision and what the best payoff is depending on the decision of other players. Aim: By presenting these interactions as a strategic game, this paper aims to provide a descriptive analysis on the utility and effectiveness of game theory in optimising decision-making in congenital cardiac care. Methodology: The comprehensive literature was searched to identify papers on game theory, and its application within surgery. Results: The analysis demonstrated that by utilising game theories, decision-making can be more aligned with patient-centric approaches, potentially improving clinical outcomes. Conclusion: Game theory is a useful tool for improving decision-making and may pave the way for more efficient and improved patient-centric approaches.

Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type I interferon response.

To overcome oxidative, inflammatory, and metabolic stress, cells have evolved cytoprotective protein networks controlled by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and its negative regulator, Kelch-like ECH associated protein 1 (Keap1). Here, using high-resolution mass spectrometry we characterize the proteomes of macrophages with altered Nrf2 status revealing significant differences among the genotypes in metabolism and redox homeostasis, which were validated with respirometry and metabolomics. Nrf2 affected the proteome following lipopolysaccharide (LPS) stimulation, with alterations in redox, carbohydrate and lipid metabolism, and innate immunity. Notably, Nrf2 activation promoted mitochondrial fusion. The Keap1 inhibitor, 4-octyl itaconate remodeled the inflammatory macrophage proteome, increasing redox and suppressing type I interferon (IFN) response. Similarly, pharmacologic or genetic Nrf2 activation inhibited the transcription of IFN-ß and its downstream effector IFIT2 during LPS stimulation. These data suggest that Nrf2 activation facilitates metabolic reprogramming and mitochondrial adaptation, and finetunes the innate immune response in macrophages.