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      A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome

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          ABSTRACT

          Introduction

          Differentiation between sepsis and systemic inflammation response syndrome (SIRS) remains a diagnostic challenge for clinicians as both may have similar clinical presentation. A quick and accurate diagnostic tool that can discriminate between these two conditions would aid in appropriate therapeutic decision-making. This prospective study was conducted to evaluate the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) and procalcitonin (PCT) in sepsis and SIRS patients.

          Materials and methods

          Eighty-eight patients were enrolled, of which 29 were SIRS and 59 were sepsis patients. The levels of suPAR and PCT were measured on the day of admission (day 1), day 3, and day 7.

          Results

          The levels of suPAR and PCT were significantly higher ( p = 0.05 and p < 0.001, respectively) in sepsis group as compared to the SIRS group. The soluble urokinase-type plasminogen activator receptor was a better diagnostic tool in predicting sepsis over PCT [area under curve (AUC) 0.89 vs 0.82] on day 1. The best cutoff for suPAR was 5.58 pg/mL [96% sensitivity and 90% negative predictive value (NPV)] and the best cut-off for PCT was 1.96 ng/mL (93.1% sensitivity and 80% NPV). However, PCT had better prognostic trends ( p = 0.006) to identify nonsurvivors in sepsis group.

          Conclusion

          Our findings suggest that both suPAR and PCT can be used as potential test tools to differentiate between SIRS and sepsis. Procalcitonin showed significant prognostic trends to identify nonsurvivors. The soluble urokinase-type plasminogen activator receptor showed better diagnostic potential than PCT on day 1.

          Clinical significance

          Both suPAR and PCT can be used as surrogate biomarkers to distinguish sepsis from SIRS. Procalcitonin showing a significant prognostic trend to identify nonsurvivors can help the clinicians to take relevant clinical decisions. Also, the use of biomarkers like PCT and suPAR could reduce the inappropriate use of antibiotics in noninfective SIRS.

          How to cite this article

          Sharma A, Ray S, Mamidipalli R, Kakar A, Chugh P, Jain R, et al. A Comparative Study of the Diagnostic and Prognostic Utility of Soluble Urokinase-type Plasminogen Activator Receptor and Procalcitonin in Patients with Sepsis and Systemic Inflammation Response Syndrome. Indian J Crit Care Med 2020;24(4):245–251.

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          Most cited references24

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          Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003.

          To determine recent trends in rates of hospitalization, mortality, and hospital case fatality for severe sepsis in the United States. Trend analysis for the period from 1993 to 2003. U.S. community hospitals from the Nationwide Inpatient Sample that is a 20% stratified sample of all U.S. community hospitals. Subjects of any age with sepsis including severe sepsis who were hospitalized in the United States during the study period. None. Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for septicemia and major organ dysfunction, we identified 8,403,766 patients with sepsis, including 2,857,476 patients with severe sepsis, who were hospitalized in the United States from 1993 to 2003. The percentage of severe sepsis cases among all sepsis cases increased continuously from 25.6% in 1993 to 43.8% in 2003 (p < .001). Age-adjusted rate of hospitalization for severe sepsis grew from 66.8 +/- 0.16 to 132.0 +/- 0.21 per 100,000 population (p < .001). Age-adjusted, population-based mortality rate within these years increased from 30.3 +/- 0.11 to 49.7 +/- 0.13 per 100,000 population (p < .001), whereas hospital case fatality rate fell from 45.8% +/- 0.17% to 37.8% +/- 0.10% (p < .001). During each study year, the rates of hospitalization, mortality, and case fatality increased with age. Hospitalization and mortality rates in males exceeded those in females, but case fatality rate was greater in females. From 1993 to 2003, age-adjusted rates for severe sepsis hospitalization and mortality increased annually by 8.2% (p < .001) and 5.6% (p < .001), respectively, whereas case fatality rate decreased by 1.4% (p < .001). The rate of severe sepsis hospitalization almost doubled during the 11-yr period studied and is considerably greater than has been previously predicted. Mortality from severe sepsis also increased significantly. However, case fatality rates decreased during the same study period.
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            Epidemiology of sepsis in Germany: results from a national prospective multicenter study.

            To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Prospective, observational, cross-sectional 1-day point-prevalence study. 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (
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              Procalcitonin increase after endotoxin injection in normal subjects.

              As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.
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                Author and article information

                Journal
                Indian J Crit Care Med
                Indian J Crit Care Med
                IJCCM
                Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine
                Jaypee Brothers Medical Publishers
                0972-5229
                1998-359X
                April 2020
                : 24
                : 4
                : 245-251
                Affiliations
                [1,5,6,8 ]Department of Research, Sir Ganga Ram Hospital, New Delhi, India
                [2 ]Department of Critical Care Medicine, Artemis Hospital, Gurugram, Haryana, India
                [3,4 ]Department of Medicine, Sir Ganga Ram Hospital, New Delhi, India
                [7 ]Department of Biotechnology, University Institute of Engineering and Technology, Maharshi Dayanand University, Rohtak, Haryana, India
                Author notes
                Sumit Ray, Department of Critical Care Medicine, Artemis Hospital, Gurugram, Haryana, India, Phone: +91-011-42252421, e-mail: drsray2014@ 123456gmail.com
                Article
                10.5005/jp-journals-10071-23385
                7297249
                02bcd31b-6bd2-4f07-a04e-a7cd322235a6
                Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.

                © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Categories
                Original Article

                Emergency medicine & Trauma
                procalcitonin,sepsis,soluble urokinase-type plasminogen activator receptor,systemic inflammation response syndrome

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