Background: Myocardial perfusion imaging by positron-emission tomography (PET MPI) is regarded as a valid technique for the diagnosis of coronary artery disease (CAD), but the incremental prognostic value of PET MPI among individuals with known or suspected CAD is not firmly established. Hypothesis: Myocardial perfusion defect sizes as measured by PET MPI using automated software will provide incremental prognostic value for cardiac and all-cause mortality. Methods: This study included 3739 individuals who underwent rest-stress rubidium-82 PET MPI for the evaluation of known or suspected CAD. Rest, stress, and stress-induced myocardial perfusion defect sizes were determined objectively by automated computer software. Study participants were followed for a mean of 5.2 years for cardiac and all-cause mortality. Cox proportional hazards models were developed to evaluate the incremental prognostic value of PET MPI. Results: A strong correlation was observed between perfusion defect sizes assessed visually and by automated software (r = 0.76). After adjusting for cardiac risk factors, known CAD, noncoronary vascular disease, and use of cardioprotective medications, stress perfusion defect size was strongly associated with cardiac death (P < 0.001). Rest perfusion defects demonstrated a stronger association with cardiac death (P < 0.001) than stress-induced perfusion defects (P = 0.01), yet both were highly significant. Similar patterns held for all-cause death. Conclusions: The current study is the largest to date demonstrating PET MPI provides incremental prognostic value among individuals with known or suspected CAD. Automated calculation of perfusion defect sizes may provide valuable supplementary information to visual assessment.

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mRNA levels for CXCR1 and CXCR2 are increased in blood in males with obstructive CAD and decreased in patients with improved perfusion, suggesting that these genes may serve as markers of disease severity and progression.

CDC2 kinase activity was decreased by up to 75% when mitotic cell free extracts from mouse fibroblasts were incubated with cAMP and ATP. This effect was blocked by PKI, the heat stable inhibitor of cAMP-dependent protein kinase (PKA). An acidic, heat stable protein from G1 cells, consistent with inhibitor-1 of protein phosphatase 1, mimicked the effect of cAMP, but was not antagonized by PKI. Okadaic acid, another inhibitor of protein phosphatase 1, also downregulated CD2 activity, and the effect was independent of both cAMP and PKI. The evidence suggests that PKA exerts its effect by activating inhibitor-1 by phosphorylation, and that the next step in the regulatory pathway requires the inactivation of one or more protein phosphatase 1 isoenzymes. Non-denaturing gel electrophoresis suggested that the size and/or charge density of the CDC2 kinase complex was changed when the activity was downregulated by cAMP or G1 extracts.

Patients are the stewards of their own care and hence their voice is important when designing and implementing research. Patients should be involved not only as participants in research that impacts their care, as the recipients of that care and any associated harms, but also as research collaborators in prioritising important questions from the patient perspective and designing the research and the ways in which is it most appropriate to involve patients. The PIONEER Consortium, an international multistakeholder collaboration lead by the European Association of Urology, has developed a core outcome set (COS) for localised and metastatic prostate cancer relevant to all stakeholders in particular patients. Throughout the work of PIONEER, patient representatives were involved as collaborators in setting the research agenda, and a wider group of patients was involved as participants in developing COSs, for instance in consensus meetings on choosing important outcomes and appropriate definitions. This publication showcases the process for COS development and highlights the most important recommendations to ultimately inform future research projects co-created between patients and other stakeholders. Patient summary: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is the development of a core outcome set (COS) that is relevant to all stakeholders. This report highlights the patient participation throughout our PIONEER COS development. Take Home Message: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is to develop a core outcome set (COS) that is relevant to all stakeholders. As part of the work of the PIONEER Consortium, we aim to highlight the patient participation throughout our PIONEER COS development.