{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:21:11Z","timestamp":1790630471810,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1417,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research"},{"name":"Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Critically ill patients admitted to an intensive care unit (ICU) exhibit a high mortality rate irrespective of the initial cause of hospitalization. Neprilysin, a neutral endopeptidase degrading an array of vasoactive peptides became a drug target within the treatment of heart failure with reduced ejection fraction. The aim of this study was to analyse whether circulating levels of neprilysin at ICU admission are associated with 30 day mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this single-centre prospective observational study, 222 consecutive patients admitted to a tertiary ICU at a university hospital were included. Blood was drawn at admission and soluble neprilysin levels were measured using ELISA. In the total cohort, soluble neprilysin levels did not differ according to survival status after 30 days as well as type of admission. However, in patients after surgery or heart valve intervention, 30 day survivors exhibited significantly lower circulating neprilysin levels as compared to those who died within 30 days (660.2, IQR: 156.4\u20132512.5 pg\/mL vs. 6532.6, IQR: 1840.1\u201310 000.0 pg\/mL; P = 0.02). Soluble neprilysin predicted mortality independently from age, gender, and commonly used scores of risk-prediction (EuroSCORE II, STS-score, and SAPS II score). Additionally, soluble neprilysin was markedly elevated in patients with sepsis and septic shock (P &amp;lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>At the time of ICU admission, circulating levels of neprilysin independently predicted 30 day mortality in patients following cardiac surgery or heart valve intervention, but not in critically ill medical patients. Furthermore, patients suffering from sepsis and septic shock displayed significantly increased circulating neprilysin levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13787","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T05:00:18Z","timestamp":1642482018000},"page":"1160-1166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Soluble Neprilysin and Survival in Critically Ill Patients"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3539-994X","authenticated-orcid":false,"given":"Max","family":"Lenz","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]},{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin A.","family":"Krychtiuk","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]},{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Brekalo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik F.","family":"Draxler","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Pavo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hengstenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Huber","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research , Vienna ,","place":["Austria"]},{"name":"3rd Medical Department, Wilhelminenhospital , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"H\u00fclsmann","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gottfried","family":"Heinz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Wojta","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]},{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research , Vienna ,","place":["Austria"]},{"name":"Core Facilities, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter S.","family":"Speidl","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna , Spitalgasse 23, Vienna, 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"2026012114165697700_ehf213787-bib-0001","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/1873-3468.13602","article-title":"Crystal structure of peptide-bound neprilysin reveals key binding interactions","volume":"594","author":"Moss","year":"2020","journal-title":"FEBS Lett"},{"key":"2026012114165697700_ehf213787-bib-0002","first-page":"449","article-title":"Effect of adsorbents on IgM and IgG measles antibodies","volume":"19","author":"Polna","year":"1975","journal-title":"Acta Virol"},{"key":"2026012114165697700_ehf213787-bib-0003","first-page":"210","article-title":"Distribution of enkephalinase (membrane metalloendopeptidase, E.C. 3.4.24.11) in rat organs. 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