Kinetics of plasma cell‐free DNA and creatine kinase in a canine model of tissue injury

Background: Cell‐free DNA (cfDNA) comprises short, double‐stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. Objectives/Hypothesis: Cell‐free DNA will have a short biological half‐life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half‐life of cfDNA and to contrast them with those of creatine kinase (CK). Animals: Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy. Methods: Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery. Results: The biological half‐life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36–7.98 hours) and 28.7 hours (CI95, 25.3–33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6–12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity. Conclusions and Clinical Importance: Plasma CK activity has a longer biological half‐life than previously thought. In contrast to plasma CK activity, cfDNA has a short half‐life and could be a useful marker for peracute severe tissue injury

Timing is Everything: Temporal Reasoning and Temporal Data Maintenance in Medicine

Both clinical management of patients and clinical research are essentially time-oriented endeavors. In this paper, I emphasize the crucial role of temporal-reasoning and temporal-maintenance tasks for modern medical information and decision support systems. Both tasks are important for management of clinical data, but the first is often approached mainly through artificial-intelligence methodologies, while the other is usually investigated by the database community. However, both tasks require careful consideration of common theoretical issues, such as the structure of time. In addition, common to both of these research areas are tasks such as temporal abstraction and management of variable temporal granularity. Finally, both tasks are highly relevant for applications such as patient monitoring, support to application of therapy guidelines, assessment of the quality of guideline application, and visualization and exploration of time-oriented biomedical data. I propose that integration of the two areas should be a major research and development goal. I demonstrate one integration approach by presenting a new architecture, a temporal mediator, which combines temporal reasoning and temporal maintenance, and integrates the management of clinical databases and medical knowledge bases. I present and discuss examples of using the temporal mediator for several of the application areas mentioned. I conclude by reemphasizing the importance of effective knowledge representation, knowledge reuse, and knowledge sharing methods to medical decision support systems in general, and to time-oriented systems in particular