**7. Conclusions**

In recent years, progress has been achieved in comprehending the biological significance of full-length CGA and selective CGA-derived peptides measured in the bloodstream of critically ill patients. These molecules will undoubtedly benefit from specific assessments in larger groups of seriously ill patients with selected clinical phenotypes. Such a prerequisite is mandatory to understand how well-conserved molecules can contribute to understanding pathophysiological conditions that are still unexplained and, therefore, not efficiently treated. For further experiments, we propose testing the implications of CGA and CGA-derived peptides in acute heart diseases and in acute neurological abnormalities that are time-dependently observed in the critically ill. In addition, given the presence of other granins, these molecules will also be investigated in a second step. If our hypotheses turn out to be correct, we believe this will open new insights into the care of the critically ill with multiple organ failure. Linking our efforts in clinical settings and ex vivo experiments will result in better use of endogenous CGA-derived peptides for diagnostic tools and synthetic CGA-derived peptides for implants in the critically ill.

**Author Contributions:** Conceptualization, F.S. (Francis Schneider); investigation, F.S. (Francis Schneider), R.C.-J., F.S. (Francesco Scavello) and T.L.; resources F.S. (Francis Schneider), Y.H. and P.L.; writing—original draft preparation, F.S. (Francis Schneider) and R.C.-J.; writing-review and editing, F.S. (Francis Schneider), A.C., T.A. and Y.H. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** This research program was possible with the help (notably through constant discussions) and the logistical support of other European research groups interested in these molecules highly conserved during evolution. We also thank INSERM U1121 and Hôpitaux Universitaires de Strasbourg, both at Strasbourg University, France, for their support.

**Conflicts of Interest:** The authors declare no conflict of interest related to this paper.
