Kompendium 2020 Forschung & Klinik

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TOP-Studien 40 tPA Serum Antigen Levels Predict ARDS in Polytraumatized Patients Acute respiratory distress syndrome (ARDS) is a highly lifethreatening, clinically defined, heterogeneous condition, regarding both etiology and clinical course, which is triggered by either a direct or an indirect insult to the lung, causing epithelial and endothelial injuries. A variety of cellular and molecular mechanisms contribute to the complex pathophysiology of ARDS, including inflammation-induced coagulation and reduced fibrinolysis, which favor excessive intra-alveolar fibrin deposition. „The choice of the right treatment strategy for polytraumatized patients has to be based on an individual risk stratification. The ambition of contributing to the implementation of a personalized polytrauma care encouraged me to establish the research group ‚Biomarkers‘ in 2011.“ Lukas Negrin Study: Negrin LL, Dedeyan M, Plesser S, Hajdu S. Impact of Polytrauma and Acute Respiratory Distress Syndrome on Markers of Fibrinolysis: A Prospective Pilot Study. Front Med (Lausanne). <strong>2020</strong> Jun 2;7:194. ARDS is a common complication in polytrauma victims, particularly in those with chest injuries, and a major cause of mortality and morbidity. Its development is difficult to anticipate, as candidate biomarkers for the prediction of ARDS were found not to be reliable for clinical use. By assessing the time-dependent course of the serum antigen levels of the tissue plasminogen activator (tPA) and the plasminogen activator inhibitor type-1 (PAI-1), which are both thought to reflect endothelial damage, we strived to identify a cut off value or a clear curve characteristic that might predict the development of ARDS in polytraumatized patients. Our prospective study enrolled 28 consecutive blunt polytrauma survivors (mean age, 38.4 [18-85] years; mean ISS, 35.1 [21-50]), who were directly admitted to our level I trauma center within one year and transferred to the ICU after initial treatment fulfilling the inclusion criteria minimum age of 18 years (1), Injury Severity Score (ISS) equal or higher than 16 (2), no anticoagulant medication before trauma (3), and no treatment with tranexamic acid (4) to avoid hyperfibrinolysis. To investigate the natural history of biomarker levels, blood samples for tPA and PAI-1 analysis using Luminex multi-analyte technology were taken at admission (day 0) and on days 1, 3, 5, 7, 10, 14, and 21 during hospitalization, as long as the patient consented. Ten healthy adults, who had responded our call for volunteers, were combined to our control group. Only one blood sample was taken from them. Mann-Whitney U-test, Chi-square test, and Wald test were performed to reveal significant differences (p 3-fold higher than the mean level of the healthy control group. After decreasing by 36% from day 0 to day 3 (p = 0.004), it basically remained stable for up to 21 days (included).
TOP-Studien 41 Figure 1: Individual tPA antigen levels (grey lines) and mean tPA antigen level (black bold line) in the study group. Mean ± standard error of the mean of tPA in healthy controls (green). tPA is secreted into the plasma primarily by vascular endothelial cells through two pathways: consecutive secretion, in which proteins are continuously released as fast as they are synthesized, and regulated secretion, in which newly synthesized tPA is stored at high concentrations in organelles and secreted only in response to an appropriate stimulus such as a vascular injury. We speculate that the physical impact at the time of injury and pathophysiological processes hereafter might trigger enhanced consecutive secretion, causing a long-term increase in biomarker levels, whereas regulated secretion might further raise this „steady-state“ level for a short period in response to additional endothelial damage. At day 0 the mean PAI-1 antigen level was 2.6-fold higher than that of healthy controls. Despite the 20% decrease from day 0 to day 5 (p = 0.007), it remained elevated for at least three weeks. Mean PAI-1 antigen levels were higher in poly trauma victims developing pneumonia compared to those not developing the complication. The Wald test calculated p = 0.128 and 0.044 for the first week and first three weeks from admission, respectively. Noteworthy, PAI-1 antigen levels increased between day 7 and day 10 in ten of 12 patients sustaining pneumonia, all ten patients also suffering from ARDS. A strong positive correlation between tPA and PAI-1 antigen levels within the first week post-trauma was revealed, indicating that tPA and PAI-1 synthesis and their clearance from circulation by hepatic cells might be biologically linked. The significant subject correlation over time between each pair of tPA antigen levels might be explained by a predominant consecutive secretion, ensuring high continuity in tPA antigen levels. Contrarily, correlation coefficients between PAI-1 antigen levels were only significant in some
Page 1 and 2: Kompendium 2020 Forschung & Klinik
Page 3 and 4: Inhalt/Impressum 3 Die Klinik 4 Edi
Page 6 and 7: Zahlen und Fakten 6 Klinische Leist
Page 9 and 10: Zahlen und Fakten 9 Hohe Ambulanzfr
Page 11 and 12: Klinik 11 Neben der Polytrauma-Vers
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Page 15 and 16: Das ÄrztInnenteam 15 Universitäts
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Page 19 and 20: Das ÄrztInnenteam 19 Medizinische
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Page 37 and 38: TOP-Studien 37 A Prediction Model f
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Page 43 and 44: 3D Biochips for Research on Inflamm
Page 45 and 46: TOP-Studien 45 Chondro-Synovial Cro
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