{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:00:16Z","timestamp":1778770816579,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010345","name":"B. Braun-Stiftung","doi-asserted-by":"publisher","award":["n.a."],"award-info":[{"award-number":["n.a."]}],"id":[{"id":"10.13039\/100010345","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heidelberg Foundation of Surgery","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Opportunistic bacterial infections are dreaded risks in patients following liver transplantation (LTX), even though patients receive an antibiotic prophylaxis. The timely recognition of such an infection may be delayed, as culture-based diagnostic methods are linked with a relevant gap in performance. We measured plasma concentrations of Delta-like canonical Notch ligand 1 (DLL1) in 93 adult patients at seven consecutive time points after liver transplantation and correlated the results to the occurrence of culture-proven bacterial infection or a complicated clinical course (composite endpoint of two or more complications: graft rejection or failure, acute kidney failure, acute lung injury, or 90-day mortality). Patients exhibited elevated plasma concentrations after liver transplantation over the whole 28 d observation time. Patients with bacterial infection showed increased DLL1 levels compared to patients without infection. Persistent elevated levels of DLL1 on day 7 and afterward following LTX were able to indicate patients at risk for a complicated course. Plasma levels of DLL1 following LTX may be useful to support an earlier detection of bacterial infections in combination with C-reactive protein (CRP) and procalcitonin (PCT), or they may lead to risk stratification of patients as a single marker for post-operative complications. (Clinical Trial Notation. German Clinical Trials Register: DRKS00005480).<\/jats:p>","DOI":"10.3390\/diagnostics10110894","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T21:39:56Z","timestamp":1604180396000},"page":"894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Delta-Like Canonical Notch Ligand 1 in Patients Following Liver Transplantation\u2014A Secondary Analysis of a Prospective Cohort Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3525-1155","authenticated-orcid":false,"given":"Sebastian O.","family":"Decker","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Hygiene, Centre for Infectious Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bruckner","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Lichtenstern","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Heeg","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Hygiene, Centre for Infectious Diseases, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus A.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, Essen University Hospital, Hufelandstra\u00dfe 55, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-7430","authenticated-orcid":false,"given":"Florian","family":"Uhle","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"key":"ref_1","first-page":"659","article-title":"Homotransplantation of the Liver in Humans","volume":"117","author":"Starzl","year":"1963","journal-title":"Surg. Gynecol. Obstet."},{"key":"ref_2","first-page":"671","article-title":"Immunosuppression after liver transplant, now and in future","volume":"59","year":"2013","journal-title":"Vnitr. Lek."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.4254\/wjh.v8.i18.749","article-title":"Quality of life after liver transplantation: State of the art","volume":"8","author":"Onghena","year":"2016","journal-title":"World J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1093\/cid\/ciz1113","article-title":"Burden and Timeline of Infectious Diseases in the First Year After Solid Organ. Transplantation in the Swiss Transplant. Cohort Study","volume":"71","author":"Stampf","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","first-page":"145","article-title":"Early Postoperative Infections after Liver Transplant","volume":"16","author":"Akdur","year":"2018","journal-title":"Exp. Clin. Transplant."},{"key":"ref_6","first-page":"7","article-title":"Biomarkers for Sepsis: What is and What Might Be?","volume":"10","author":"Biron","year":"2015","journal-title":"Biomark. Insights"},{"key":"ref_7","first-page":"1179","article-title":"Prognostic Value of Procalcitonin, CRP, Serum Amyloid A, Lactate and IL-6 Markers in Liver Transplant Patients Admitted to ED with Suspected Infection","volume":"31","author":"Turtay","year":"2017","journal-title":"In Vivo"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1016\/j.transproceed.2014.08.048","article-title":"Kinetics of interleukin-6, procalcitonin, and C-reactive protein after pediatric liver transplantation","volume":"46","author":"Zant","year":"2014","journal-title":"Transplant. Proc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/00003643-201406001-00599","article-title":"Procalcitonin after liver transplantation. Kinetics and correlation with postoperative complications: 12AP5-10","volume":"31","author":"Agudo","year":"2014","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fcimb.2018.00241","article-title":"The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes","volume":"8","author":"Hildebrand","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3389\/fcimb.2019.00267","article-title":"Host-Derived Delta-Like Canonical Notch Ligand 1 as a Novel Diagnostic Biomarker for Bacterial Sepsis-Results From a Combinational Secondary Analysis","volume":"9","author":"Hildebrand","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00423-019-01769-y","article-title":"New approaches for the detection of invasive fungal diseases in patients following liver transplantation-results of an observational clinical pilot study","volume":"404","author":"Decker","year":"2019","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_13","unstructured":"Heidelberg University Hospital (2006). Heidelberger Manual der Lebertransplantation, Heidelberg University Hospital. [2nd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/j.1600-6143.2005.01207.x","article-title":"American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation","volume":"6","author":"Humar","year":"2006","journal-title":"Am. J. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1111\/ajt.13909","article-title":"2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection","volume":"16","author":"Demetris","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin. Pract."},{"key":"ref_17","first-page":"2526","article-title":"Acute respiratory distress syndrome: The Berlin Definition","volume":"307","author":"Force","year":"2012","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1056\/NEJMra064928","article-title":"Infection in solid-organ transplant recipients","volume":"357","author":"Fishman","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.3748\/wjg.v20.i20.6211","article-title":"Bacterial infection after liver transplantation","volume":"20","author":"Kim","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.surg.2018.04.039","article-title":"Early mortality after liver transplantation: Defining the course and the cause","volume":"164","author":"Bagante","year":"2018","journal-title":"Surgery"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1097\/CCM.0b013e31827e83af","article-title":"Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012","volume":"41","author":"Dellinger","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1097\/CCM.0000000000001249","article-title":"Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections","volume":"43","author":"Vincent","year":"2015","journal-title":"Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1128\/JCM.00745-12","article-title":"Multiplex PCR for rapid and improved diagnosis of bloodstream infections in liver transplant recipients","volume":"50","author":"Rath","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_24","first-page":"1237","article-title":"Daily serum inflammatory cytokine (tumor necrosis factor-alpha, interleukin-6) monitoring in liver transplantation focusing on allograft rejection: A five-case report","volume":"28","author":"Kita","year":"1996","journal-title":"Transplant. Proc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/s41467-017-00953-2","article-title":"Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia","volume":"8","author":"Krishnasamy","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7638","DOI":"10.1073\/pnas.1230693100","article-title":"The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase","volume":"100","author":"Six","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1074\/jbc.M605451200","article-title":"Proteolytic processing of delta-like 1 by ADAM proteases","volume":"282","author":"Dyczynska","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1111\/ajt.15141","article-title":"Circulating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppression","volume":"19","author":"Norum","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/01.tp.0000234905.56926.7f","article-title":"Induction immunosuppression","volume":"82","author":"Kirk","year":"2006","journal-title":"Transplantation"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bush, W.W. (1999). Overview of transplantation immunology and the pharmacotherapy of adult solid organ transplant recipients: Focus on immunosuppression. AACN Clin. Issues, 10.","DOI":"10.1097\/00044067-199905000-00011"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.4254\/wjh.v7.i10.1355","article-title":"Review on immunosuppression in liver transplantation","volume":"7","author":"Moini","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00204-014-1247-1","article-title":"Pharmacology and toxicology of mycophenolate in organ transplant recipients: An update","volume":"88","author":"Staatz","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/ki.2008.487","article-title":"Inhibition of JAK2 protects renal endothelial and epithelial cells from oxidative stress and cyclosporin A toxicity","volume":"75","author":"Neria","year":"2009","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.cardfail.2015.07.012","article-title":"Increased Serum Levels of the Notch Ligand DLL1 are Associated with Diastolic Dysfunction, Reduced Exercise Capacity, and Adverse Outcome in Chronic Heart Failure","volume":"22","author":"Norum","year":"2016","journal-title":"J. Card. Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s12265-017-9748-y","article-title":"The Notch Ligands DLL1 and Periostin Are Associated with Symptom Severity and Diastolic Function in Dilated Cardiomyopathy","volume":"10","author":"Norum","year":"2017","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Berg, J., Halvorsen, A.R., Bengtson, M.-B., Task\u00e9n, K.A., Maelandsmo, G.M., Yndestad, A., Halvorsen, B., Brustugun, O.T., Aukrust, P., and Ueland, T. (2018). Levels and prognostic impact of circulating markers of inflammation, endothelial activation and extracellular matrix remodelling in patients with lung cancer and chronic obstructive pulmonary disease. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4659-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/lt.22165","article-title":"Posttransplant bacteremia in adult living donor liver transplant recipients","volume":"16","author":"Iida","year":"2010","journal-title":"Liver Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/lt.20215","article-title":"Risk factors for renal dysfunction in the postoperative course of liver transplant","volume":"10","author":"Gallardo","year":"2004","journal-title":"Liver Transplant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.jhep.2013.11.028","article-title":"Notch signaling and new therapeutic options in liver disease","volume":"60","author":"Morell","year":"2014","journal-title":"J. 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