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Background <p>Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) is increasingly recognised as a critical contributor to adverse outcomes in critically ill patients, yet its clinical implications in paediatric populations remain under-explored. The aim of this study was to apply the established PICS diagnostic criteria to a cohort in a paediatric intensive care unit (PICU) to identify clinical factors associated with mortality and characterise phenotype with distinct outcomes.</p> Methods <p>We conducted a retrospective analysis of 536 PICU patients admitted for ≥ 15 days between 2019 and 2024 at a single tertiary centre. Paediatric PICS was defined as elevated C-reactive protein (&gt; 2.0&#xa0;mg·dL<sup>–1</sup>), hypoalbuminaemia (&lt; 3.0&#xa0;g·dL<sup>–1</sup>), and lymphopenia (&lt; 800 µL<sup>–1</sup>) on days 13–15. Twenty-two clinical variables measured at or around day 14 were analysed using principal component analysis (PCA) followed by k-means clustering of retained principal component scores. Weighted clustering using the original variables was performed as a sensitivity analysis. Survival differences between PCA-derived phenotypes were assessed using Kaplan–Meier analysis.</p> Results <p>Paediatric PICS was diagnosed in 64 patients (11.9%), who exhibited higher mortality rates (42% vs. 15%). PCA-based clustering identified three clusters (interpreted as phenotypes) with distinct mortality gradients. The first principal component represented a high-risk axis characterised by greater organ dysfunction, hyperbilirubinaemia, coagulopathy, metabolic derangement, and thrombocytopenia. A concordant high-risk phenotype was reproduced in the weighted-clustering sensitivity analysis. In the PCA-based main analysis, 1-year survival differed significantly across three clusters (log-rank χ² = 11.85, <i>P</i> = 0.0027).</p> Conclusions <p>Paediatric PICS appears to be phenotypically heterogeneous and may include higher-risk phenotypes. These findings are exploratory and require external validation before clinical implementation.</p> Graphical Abstract <p></p>

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Mortality-associated high-risk phenotype in paediatric persistent inflammation, immunosuppression, and catabolism syndrome: single-centre retrospective cohort study, 2019–2024

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  • 发表日期：

    2026年5月22日

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  • Soichiro Tanimura,
  • Norihiko Tsuboi,
  • Eisaku Nashiki,
  • Saki Endo,
  • Shin Tsubokura,
  • Shotaro Matsumoto

摘要

Background

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) is increasingly recognised as a critical contributor to adverse outcomes in critically ill patients, yet its clinical implications in paediatric populations remain under-explored. The aim of this study was to apply the established PICS diagnostic criteria to a cohort in a paediatric intensive care unit (PICU) to identify clinical factors associated with mortality and characterise phenotype with distinct outcomes.

Methods

We conducted a retrospective analysis of 536 PICU patients admitted for ≥ 15 days between 2019 and 2024 at a single tertiary centre. Paediatric PICS was defined as elevated C-reactive protein (> 2.0 mg·dL–1), hypoalbuminaemia (< 3.0 g·dL–1), and lymphopenia (< 800 µL–1) on days 13–15. Twenty-two clinical variables measured at or around day 14 were analysed using principal component analysis (PCA) followed by k-means clustering of retained principal component scores. Weighted clustering using the original variables was performed as a sensitivity analysis. Survival differences between PCA-derived phenotypes were assessed using Kaplan–Meier analysis.

Results

Paediatric PICS was diagnosed in 64 patients (11.9%), who exhibited higher mortality rates (42% vs. 15%). PCA-based clustering identified three clusters (interpreted as phenotypes) with distinct mortality gradients. The first principal component represented a high-risk axis characterised by greater organ dysfunction, hyperbilirubinaemia, coagulopathy, metabolic derangement, and thrombocytopenia. A concordant high-risk phenotype was reproduced in the weighted-clustering sensitivity analysis. In the PCA-based main analysis, 1-year survival differed significantly across three clusters (log-rank χ² = 11.85, P = 0.0027).

Conclusions

Paediatric PICS appears to be phenotypically heterogeneous and may include higher-risk phenotypes. These findings are exploratory and require external validation before clinical implementation.

Graphical Abstract