Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study*

Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck; Ellekilde, Gertrude; Eugen‐Olsen, Jesper; Andersen, Ove

doi:10.1097/ccm.0000000000003441

Cited by 52 publications

(92 citation statements)

References 26 publications

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“…From a clinical point of view, this marker has been linked to quite a range of complications and adverse prognosis in manifold disease settings [4,8,31], and even in seemingly healthy volunteers [32,33]. The ability of suPAR to help in risk stratification is particularly interesting in the emergency room [34,35] or the ICU setting [18,36], where acutely ill patients require an early risk assessment to tailor therapeutic interventions and allocate appropriate ICU resources. However, despite its practical utility for prognostication in the ICU setting, suPAR appears to be quite non-specific as to the cause of disease, to the presence of sepsis and to the nature of concomitant organ failure(s) [30].…”

Section: Discussionmentioning

confidence: 99%

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

et al. 2019

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Background: Circulating levels of soluble urokinase plasminogen activation receptor (suPAR) have been proposed as a prognostic biomarker in patients with critical illness and sepsis. However, the origin of suPAR in sepsis has remained obscure. We investigated the potential cellular sources of suPAR by analyzing membrane-bound urokinase plasminogen activator receptor (uPAR, CD87) and evaluated its clinical relevance in critically ill patients. Methods: We studied 87 critically ill patients (44 with sepsis, 43 without sepsis) from the medical intensive care unit (ICU) in comparison to 48 standard care patients with infections and 27 healthy controls in a prospective single-center noninterventional cohort study. Cellular uPAR expression of different immune cell subsets (by flow cytometry from peripheral blood) and corresponding serum suPAR concentrations were determined upon ICU admission and at day 3. Furthermore, we analyzed the effects of serum from sepsis patients on the activation and uPAR cleavage of primary human neutrophils and macrophages in vitro. Results: In healthy controls, uPAR (CD87) expression was detected on nearly all blood neutrophils and monocytes, but only scarcely on lymphocytes. While uPAR expression on monocytes was maintained in ICU patients, only 58% of neutrophils from critically ill patients expressed uPAR, which was significantly lower than in healthy controls or standard care patients. Concomitantly, serum suPAR levels were significantly increased in ICU patients. We noted a clear inverse correlation between low neutrophilic uPAR and high serum suPAR in standard care and ICU patients, indicating that shedding of uPAR from activated neutrophils represents a main source of suPAR in systemic inflammation. Both low uPAR and high suPAR were closely associated with mortality in critically ill patients. Furthermore, serum from sepsis patients induced uPAR protein expression and subsequent receptor shedding on isolated primary neutrophils, but not on macrophages, in vitro. Conclusions: The inverse correlation between low uPAR surface expression on neutrophils and high serum suPAR in critically ill patients supports that neutrophils are a main source of shed suPAR proteins in systemic inflammation. Furthermore, high suPAR levels and low neutrophilic uPAR expression predict mortality in ICU patients.

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Section: Discussionmentioning

confidence: 99%

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

et al. 2019

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“…Some studies have reported that the predictive ability of the NEWS increases on combining several lab-oratory results with the NEWS. 9,[20][21][22] This combination method should also be validated in older patients to improve predictive ability in this patient group.…”

Section: Discussionmentioning

confidence: 99%

Use of the National Early Warning Score for predicting in-hospital mortality in older adults admitted to the emergency department

et al. 2020

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Objective The National Early Warning Score (NEWS), based on the patients' vital signs, detects clinical deterioration in critically ill patients and is used to reduce the incidence of in-hospital cardiac arrest. However, although mortality prediction based on vital signs may be difficult in older patients, the effectiveness of the NEWS has not yet been evaluated in this population. This study aimed to test the hypothesis that an elevated NEWS at admission increases the mortality risk in older patients admitted to the emergency department (ED). Methods We conducted a single-center retrospective study, including patients admitted to the ED between November 2016 and February 2017. We included patients aged > 65 years who were admitted to the ED for any medical problem. The NEWS was calculated at the time of ED admission. The primary outcome was in-hospital mortality. Results In total, 3,169 patients were included in this study. Median age was 75 years (interquartile range [IQR], 70 to 80 years), and 1,557 (49.1%) patients were male. The in-hospital mortality rate was 5.1% (161 patients). Median NEWS was higher in non-survivors than in survivors (5 [IQR, 3-8] vs. 1 [IQR, 0-3], P < 0.001). Multivariate logistic analysis showed that the NEWS was associated with in-hospital mortality, after adjusting for other confounders. The area under the curve of the NEWS for predicting in-hospital mortality was 0.820 (95% confidence interval, 0.806 to 0.833). Conclusion Our results show that the NEWS at admission is associated with in-hospital mortality among patients aged > 65 years.

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“…The available test allows a fast prognosis for patients, as the results can quickly be obtained on-site in the emergency room or other in-hospital settings, avoiding the need for samples to be passed through the clinical laboratory, or can even be obtained prior to hospitalization (time to result 20 min). Based on the aforementioned evidence, the suPAR could serve as a quick triage test and independent marker of clinical severity, 30-day readmission, complications, and mortality in this pandemic [10,19,35,36]. We believe that the results of ongoing trials in Germany, the UK, Denmark, Greece, and the USA will be important for clinicians worldwide.…”

Section: Soluble Urokinase Plasminogen Activator Receptormentioning

confidence: 98%

“…In a study of 42,452 acutely presenting patients, suPAR had the highest area under the curve of all investigated individual predictors, including C-reactive protein (CRP), while there was no significant difference in the predictive value between age groups [9]. In another study, including 17,312 acutely admitted medical patients, the addition of suPAR to National Early Warning Score significantly improved risk prediction of both low-and highrisk acute medical patients [10]. Interestingly, patients with low National Early Warning Score, but elevated suPAR had mortality risks comparable to that of patients with higher National Early Warning Score.…”

Section: Soluble Urokinase Plasminogen Activator Receptormentioning

confidence: 99%

Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients

et al. 2020

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The novel coronavirus infection has spread worldwide, causing a wide spectrum of clinical manifestations. Most patients develop moderate clinical illness, but a substantial number will experience severe pneumonia, which may rapidly progress to acute respiratory distress syndrome and multiple organ failure. In this population, soluble urokinase plasminogen activator receptor (suPAR) could serve as a quick triage test and independent marker of clinical severity, hospital and intensive care unit admission, complications, and mortality.

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Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study*

Abstract: Supplemental Digital Content is available in the text.

Cited by 52 publications

References 26 publications

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

Neutrophils are a main source of circulating suPAR predicting outcome in critical illness

Use of the National Early Warning Score for predicting in-hospital mortality in older adults admitted to the emergency department

Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients

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