Prof. Dr. Gregor Theilmeier
Perioperative Inflammation and Infection
Department of Human Medicine
Faculty of Medicine and Health Sciences
University of Oldenburg

Prof. Dr. Thomas W.L. Scheeren
Department of Anesthesiology
UMCG

Dr. Matijs van Meurs
Intensive Care MedicineLab at:
Dept. Pathology, Medical Biology division
Endothelial Biomedicine & Vascular
Drug Targeting research
UMCG

Sophie Ellermann, M.Sc.
PhD Student

Summary: More than 10% of the adult population undergoes surgery every year. Accompanying diseases become more frequent as the population ages. They drive complications after surgery. Complications after surgery become an increasingly important entity, because they affect the benefit of surgical treatment. Complications are difficult to diagnose and hard to treat and have grave consequences for the patient. Affected organs comprise kidney, liver, lung, cardiovascular system and the central nervous system. Complications in different organs seem to interact. One of the main causes of organ dysfunction after surgery is the disturbance of microvascular function. Functional tests for microvascular dysfunction are increasingly becoming available, but plasmatic biomarkers for this condition are unavailable. Preexisting microvascular dysfunction as a predictor for adverse outcome has been studied in sepsis, but has scarcely been addressed in surgical outcome studies. In a biobank in 1500 patients undergoing major surgery we will link microvascular function and plasmatic biomarkers with adverse outcomes after major surgery. Furthermore, we will use the samples to assess their predictiveness for adverse outcomes as a basis for future planning of interventional studies. By comparing biosamples from patients suffering complications compared to those who did not, we will identify a limited number of candidate molecules as biomarkers and therapeutic targets for further studies in vivo and in vitro studies. Therefore the samples are used in ex vivo organ models of the cardiovascular and renal vasculature to study the regulatory integration of identified candidates into endothelial biology with emphasis on endothelial heterogeneity in these organs. Individual candidate molecules will be studied as therapeutic targets to prevent postoperative complications in animal models. With this translational approach we aim to predict, prevent and treat complications after surgery.

Publications:

• Na, J., Newman, J. A., Then, C. K., Syed, J., Vendrell, I., Torrecilla, I., Ellermann, S., Ramadan, K., Fischer, R., & Kiltie, A. E. (2021). SPRTN protease-cleaved MRE11 decreases DNA repair and radiosensitises cancer cells. Cell death & disease, 12(2), 165.