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Meta-Analysis
. 2023 Dec;51(6):1797-1807.
doi: 10.1007/s15010-023-02093-w. Epub 2023 Sep 14.

Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: a systematic review and individual patient level meta-analysis

Patrick Zuercher #  1 , André Moser #  2 , Luis Garcia de Guadiana-Romualdo  3 , Martin J Llewelyn  4 , Rolf Graf  5 , Theresia Reding  5 , Philippe Eggimann  6 , Yok-Ai Que  1 , Josef Prazak  7
Affiliations
Meta-Analysis

Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: a systematic review and individual patient level meta-analysis

Patrick Zuercher et al. Infection. 2023 Dec.

Abstract

Background: Several studies suggested pancreatic stone protein (PSP) as a promising biomarker to predict mortality among patients with severe infection. The objective of the study was to evaluate the performance of PSP in predicting intensive care unit (ICU) mortality and infection severity among critically ill adults admitted to the hospital for infection.

Methods: A systematic search across Cochrane Central Register of Controlled Trials and MEDLINE databases (1966 to February 2022) for studies on PSP published in English using 'pancreatic stone protein', 'PSP', 'regenerative protein', 'lithostatin' combined with 'infection' and 'sepsis' found 46 records. The search was restricted to the five trials that measured PSP using the enzyme-linked immunosorbent assay technique (ELISA). We used Bayesian hierarchical regression models for pooled estimates and to predict mortality or disease severity using PSP, C-Reactive Protein (CRP) and procalcitonin (PCT) as main predictor. We used statistical discriminative measures, such as the area under the receiver operating characteristic curve (AUC) and classification plots.

Results: Among the 678 patients included, the pooled ICU mortality was 17.8% (95% prediction interval 4.1% to 54.6%) with a between-study heterogeneity (I-squared 87%). PSP was strongly associated with ICU mortality (OR = 2.7, 95% credible interval (CrI) [1.3-6.0] per one standard deviation increase; age, gender and sepsis severity adjusted OR = 1.5, 95% CrI [0.98-2.8]). The AUC was 0.69 for PSP 95% confidence interval (CI) [0.64-0.74], 0.61 [0.56-0.66] for PCT and 0.52 [0.47-0.57] for CRP. The sensitivity was 0.96, 0.52, 0.30 for risk thresholds 0.1, 0.2 and 0.3; respective false positive rate values were 0.84, 0.25, 0.10.

Conclusions: We found that PSP showed a very good discriminative ability for both investigated study endpoints ICU mortality and infection severity; better in comparison to CRP, similar to PCT. Combinations of biomarkers did not improve their predictive ability.

Keywords: Biomarker; Infection; Mortality; PSP; Pancreatic stone protein.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work. RG has received research grants from Gebert Rüf Foundation, in addition, Dr. Graf has a patent method for assaying sepsis and outcome in humans by detection of PSP/reg licensed to LASCCO. DS reports grants from Astra-Zeneca AG, Curetis AG, Boston Scientific, other from Astra-Zeneca AG, Novartis AG, GSK AG, Roche AG, Zambon, Pfizer and Schwabe Pharma AG, Vifor AG, outside the submitted work. PE has received research grants from Abionic outside the submitted work.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
ICU mortality meta-analysis
Fig. 3
Fig. 3
ICU mortality classification plot*.* Panel A: Sensitivity by risk threshold; Panel B: 1-Specificity by risk threshold; Risk threshold values shown for Youden index
Fig. 4
Fig. 4
Combined endpoint sepsis and septic shock meta-analysis
Fig. 5
Fig. 5
Combined endpoint sepsis and septic shock classification plot*. * Panel A: Sensitivity by risk threshold; Panel B: 1-Specificity by risk threshold; Risk threshold values shown for Youden index
See this image and copyright information in PMC

References

    1. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–377. doi: 10.1007/s00134-017-4683-6. - DOI - PubMed
    1. Greer O, Shah NM, Sriskandan S, Johnson MR. Sepsis: precision-based medicine for pregnancy and the puerperium. Int J Mol Sci. 2019;20:5388. doi: 10.3390/ijms20215388. - DOI - PMC - PubMed
    1. Aletaha D. Precision medicine and management of rheumatoid arthritis. J Autoimmun. 2020;110:102405. doi: 10.1016/j.jaut.2020.102405. - DOI - PubMed
    1. Ho D, Quake SR, McCabe ERB, Chng WJ, Chow EK, Ding X, Gelb BD, Ginsburg GS, Hassenstab J, Ho CM, et al. Enabling technologies for personalized and precision medicine. Trends Biotechnol. 2020;38:497–518. doi: 10.1016/j.tibtech.2019.12.021. - DOI - PMC - PubMed
    1. Seppälä TT, Zimmerman JW, Suri R, Zlomke H, Ivey GD, Szabolcs A, Shubert CR, Cameron JL, Burns WR, Lafaro KJ, et al. Precision medicine in pancreatic cancer: patient-derived organoid pharmacotyping is a predictive biomarker of clinical treatment response. Clin Cancer Res. 2022;28:3296–3307. doi: 10.1158/1078-0432.CCR-21-4165. - DOI - PMC - PubMed