Host-derived delta-like canonical notch ligand-1 in sepsis and septic shock: infection site, pathogens and disease severity matter - secondary analysis of data from a randomized controlled trial

Background - Sepsis is a life-threatening condition and many biomarkers for diagnosing and treatment guidance have been investigated in recent years. However, new ones are emerging almost daily, only few markers with diagnostic value have passed to entered clinical routine application. Delta-like ca...

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Main Authors: Theobald, Vivienne (Author) , Bloos, Frank (Author) , Bauer, Michael (Author) , Brenner, Thorsten (Author) , Forst, Maik von der (Author) , Meybohm, Patrick (Author) , Schenz, Judith (Author) , Schmitt, Felix (Author) , Siegler, Benedikt Hermann (Author) , Weigand, Markus A. (Author) , Dietrich, Maximilian (Author)
Format: Article (Journal)
Language:English
Published: April 2025
In: Journal of infection
Year: 2025, Volume: 90, Issue: 4, Pages: 1-9
ISSN:1532-2742
DOI:10.1016/j.jinf.2025.106458
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jinf.2025.106458
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0163445325000520
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Author Notes:Vivienne Theobald, Frank Bloos, Michael Bauer, Thorsten Brenner, Maik von der Forst, Patrick Meybohm, Judith Schenz, Felix C.F. Schmitt, Benedikt Siegler, Markus A. Weigand, Maximilian Dietrich, for the SepNet Critical Care Trials Group

MARC

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520 |a Background - Sepsis is a life-threatening condition and many biomarkers for diagnosing and treatment guidance have been investigated in recent years. However, new ones are emerging almost daily, only few markers with diagnostic value have passed to entered clinical routine application. Delta-like canonical Notch ligand-1 (DLL-1) seems to be a potential contributor in the differentiation between sepsis and non-septic infection. Its role for clinical application and potential septic outcome prediction is yet unclear. - Methods - This study is a secondary analysis of data and DLL-1 measurements from plasma samples obtained in the SISPCT trial. Primary objective of this explorative study was to investigate the difference of DLL-1 values between patients with sepsis and septic shock. Secondary objectives were the differences in DLL-1 levels in patients with different blood culture results, with infections caused by different pathogens, by origin of infection and disease severity. Furthermore, the study investigated the use of DLL-1 for in-hospital and intensive care unit (ICU) mortality prediction. Therefore, data from 1.027 patients were analyzed. - Results - DLL-1 values were significantly higher in patients with septic shock than in septic patients (13,003 ± 7695 pg/mL and 9257 ± 4188 pg/mL, p<0.001). Patients with abdominal infections, primary bacteremia or surgical wound infections exhibited the highest DLL-1 values. In addition, patients with gram-negative pathogens had significantly higher DLL-1 levels than those with specific gram-positive pathogens or negative blood cultures (p<0.001). Infections caused by Escherichia coli, Enterobacterales, and Staphylococcus aureus were associated with the highest DLL-1 levels (18,341 pg/mL, (12,968; 23,250), 21,556 pg/mL (14,386; 30,939) and 16,352 pg/mL (11,905; 25,853), respectively). DLL-1 levels correlated with increasing SOFA scores and demonstrated predictive value for in-hospital and ICU mortality, with an AUC of 0.7, outperforming lactate and procalcitonin. - Conclusion - Delta-like canonical Notch ligand-1 (DLL-1) is increased in septic shock compared to sepsis. Its elevation appears to be dependent on the infection focus, the triggering pathogen and the disease severity. Furthermore, it has a predictive value for mortality. 
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650 4 |a Host-Derived Delta-Like Canonical Notch Ligand-1 
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650 4 |a Sepsis 
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