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Diagnostic performance of calprotectin and APPY-1 test in pediatric acute appendicitis: a systematic review and a meta-analysis

  • Review Article
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European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

A Correction to this article was published on 05 July 2022

This article has been updated

Abstract

Background

Pediatric acute appendicitis (AA) is a challenging pathology to diagnose. In the last decades, multiple biomarkers have been evaluated in different human biological samples to improve diagnostic performance. This study aimed to examine the diagnostic performance of serum, fecal and urinary calprotectin as well as the role of the APPY-1 biomarker panel in pediatric acute appendicitis.

Methods

We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and two random-effect meta-analyses, one for serum calprotectin and one for APPY-1, were performed.

Results

The research resulted in 173 articles. Thirty-eight duplicates were removed. Among the remaining 135 articles, we excluded 125 following the inclusion and exclusion criteria, resulting in the 10 studies included in this review. This systematic review included data from of 3901 participants (1276 patients with confirmed diagnosis of AA and 2625 controls). The age of the participants ranged from 0 to 21 years. Four of the studies compared serum calprotectin values and reported significant differences between groups, but inconsistent results regarding cutoff points, sensitivity and specificity. Two publications compared urinary values of calprotectin and presented inconsistent results regarding sensitivity and specificity as well. One publication evaluated the diagnostic performance of fecal calprotectin, but it did not provide data on measured values. Four studies evaluated the diagnostic performance of APPY-1 test in pediatric acute appendicitis. The calculated pooled sensitivity and specificity of those studies were 97.37 (95% CI 95.60–98.44) and 36.74 (95% CI 32.28–41.44), respectively, and the calculated pooled NLR, 0.0714 (95% CI 0.041–0.115).

Conclusion

Serum calprotectin has limited diagnostic yield in pediatric acute appendicitis. Its performance seems to increase with the hours of clinical evolution and in advanced AA, although the evidence is limited. There is not enough evidence on the usefulness of urinary or fecal calprotectin in the diagnosis of pediatric acute appendicitis. On the other hand, the APPY-1 is a reliable test to exclude the diagnosis of AA in patients at low or moderate risk according to PAS and Alvarado Score.

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Data availability

The data used to carry out this systematic review are available upon request from the review authors.

Change history

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Acknowledgements

No acknowledgements to report.

Funding

This review did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. None of the authors has external funding to declare.

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Authors and Affiliations

  1. Pediatric Surgery Department, Hospital Universitario de Navarra, Pamplona, Spain

    Javier Arredondo Montero, Carlos Bardají Pascual & Giuseppa Antona

  2. School of Medicine, Department of Preventive Medicine and Public Health, University de Navarra, Calle Irunlarrea 1, 31008, Pamplona, Navarra, Spain

    Nerea Martín-Calvo

  3. IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain

    Nerea Martín-Calvo

  4. Pathology Department, Hospital Universitario de Navarra, Pamplona, Spain

    Mónica Bronte Anaut

  5. Cardiovascular Translational Research, NavarraBiomed (Miguel Servet Foundation), Hospital Universitario de Navarra, Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain

    Natalia López-Andrés

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  1. Javier Arredondo Montero
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Contributions

JAM: Conceptualization and study design; literature search and selection, data curation and extraction, formal analysis; investigation; methodology; project administration; resources; validation; visualization; writing—original draft; writing—review and editing. CBP: Literature search and selection, data curation and extraction; investigation; writing—original draft. MBA: Literature search and selection, data curation and extraction, formal analysis; investigation; writing—original draft. GA: Literature search and selection, data curation and extraction; investigation; writing—original draft. NMC: Conceptualization and study design; literature search and selection, data curation and extraction, formal analysis; investigation; methodology; project administration; resources; validation; visualization; writing—original draft; writing—review and editing.

Corresponding author

Correspondence to Nerea Martín-Calvo.

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The authors declare that they have no conflict of interest. No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Ethical approval

This study did not involve the participation of human or animal subjects, and therefore, was exempt from formal assessment by the ethics committee for clinical research of our center.

Additional information

The original online version of this article was revised due to a retrospective Open Access cancellation.

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Arredondo Montero, J., Bardají Pascual, C., Antona, G. et al. Diagnostic performance of calprotectin and APPY-1 test in pediatric acute appendicitis: a systematic review and a meta-analysis. Eur J Trauma Emerg Surg 49, 763–773 (2023). https://doi.org/10.1007/s00068-022-02000-2

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