C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome

  • Kensuke NakamuraEmail author
  • Kentaro Ogura
  • Hidehiko Nakano
  • Hiromu Naraba
  • Yuji Takahashi
  • Tomohiro Sonoo
  • Hideki Hashimoto
  • Naoto Morimura



Among patients surviving treatment in intensive care units (ICU), some cases exist for which inflammation persisted with prolonged hospital stays, referred as persistent inflammatory, immunosuppressed, catabolic syndrome (PIICS). C reactive protein (CRP) is regarded as the most important marker for PIICS. Nevertheless, the applicable cut-off of CRP for PIICS has never been described in the literature.


Data of patients admitted to the ICU/Emergency ward from May 2015 through June 2019 were analyzed retrospectively. Using K-means clustering, a 14-day CRP transition dataset was analyzed and categorized finally into 7 classes: 4 PIICS classes and 3 non-PIICS classes. Outcomes and the other PIICS characteristics were evaluated.


From all 5513 admitted patients, this study examined data of 539 patients who had been admitted for more than 14 days, and for whom 14 day CRP transition analysis could be performed. By the CRP transitions of 7 categorized classes, the CRP cut-off for PIICS was regarded as 3.0 mg/dl on day 14. The Barthel Index at discharge, albumin, and total lymphocyte counts on day 14 were significantly lower in PIICS classes than those of non-PIICS classes. Creatinine kinase, antithrombin activity and thrombomodulin on admission were regarded as independent risk factors for PIICS.


Among patients with prolonged hospital stay, the PIICS population had elevated CRP, but lower Barthel Index, albumin, and total lymphocyte counts. The criterion of day 14 CRP for PIICS should be 3.0 mg/dl.




Compliance with ethical standards

Conflicts of interest

The authors state that they have no conflict of interest. Kentaro Ogura and Tomohiro Sonoo are employed by TXP Medical Co. Ltd.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Emergency and Critical Care MHiedicineHitachi General HospitalHitachiJapan
  2. 2.Faculty of MedicineThe University of TokyoTokyoJapan
  3. 3.TXP Medical Co. LtdTokyoJapan
  4. 4.Department of Emergency and Critical Care MedicineThe University of Tokyo HospitalTokyoJapan

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