The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
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Vincenzo Roccaforte
, Giovanni Sabbatini
, Angelo Pezzi
Abstract
Objectives
The aim of the study was to evaluate the predictive value of cell population data (CPD) parameters in comparison with procalcitonin (PCT) and C-reactive protein (CRP) for an early diagnosis of sepsis in intensive care unit (ICU). The effect of renal function on CPD, PCT and CRP, in septic and non-septic patients was also investigated.
Methods
This is a retrospective, observational and single-center study, performed with data collected from patients consecutively admitted to the ICU of the Edoardo Bassini Hospital in Milan. Patients were divided in septic and non-septic according to Sepsis-III criteria. The control group was formed by critically ill patients without sepsis. Patients with sepsis were further divided in patients with sepsis and patients with septic shock.
Results
A significant difference between septic and non-septic patients was found for neutrophils complexity (NE-SSC), neutrophils fluorescence intensity (NE-SFL), width of dispersion of neutrophils fluorescence (NE-WY), monocytes complexity (MO-X), monocytes fluorescence intensity (MO-Y), PCT and CRP parameters. PCT, neutrophils sixe (NE-FSC), NE-WY, width of dispersion of neutrophils size (NE-WZ) and MO-X discriminated sepsis and septic-shock patients. CPD parameters were not influenced by renal function. CPD, PCT and CRP had a heterogeneous diagnostic performance efficiency in the prediction of sepsis. Overall, NE-SSC, NE-SFL, width of dispersion of neutrophils complexity (NE-WX), MO-X, MO-Y, PCT and CRP displayed the best diagnostic performance for sepsis.
Conclusions
This study suggested that some CPD parameters (i.e., NE-SFL and MO-X) might provide useful information for diagnosis and management of sepsis.
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Research ethics: This study was approved by the Ethics Committee of Milano Area 3 (Reference No.4801/2024, September 11, 2024) in accordance with the Declaration of Helsinki (2013 revision).
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Informed consent: Written informed consent was waived because of the retrospective nature of the study and data were treated anonymously according to the General Data Protection Regulation-GDPR UE 679/2016.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: None declared.
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Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
1. Singer, M, Deutschman, CS, Seymour, CW, Shankar-Hari, M, Annane, D, Bauer, M, et al.. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801–10. https://doi.org/10.1001/jama.2016.0287.Search in Google Scholar PubMed PubMed Central
2. Chiu, C, Legrand, M. Epidemiology of sepsis and septic shock. Curr Opin Anaesthesiol 2021;34:71–6. https://doi.org/10.1097/ACO.0000000000000958.Search in Google Scholar PubMed
3. WHO. Global Report on the Epidemiology and Burden of Sepsis: Current Evidence. Identifying gaps and future directions. Geneva, Switzerland: World Health Organization; 2020.Search in Google Scholar
4. Liu, V, Escobar, GJ, Greene, JD, Soule, J, Whippy, A, Angus, DC, et al.. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA 2014;312:90–2. https://doi.org/10.1001/jama.2014.5804.Search in Google Scholar PubMed
5. Torio, CM, Moore, BJ. National inpatient hospital costs: the most expensive conditions by Payer, 2013. 2016 May. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006. Statistical Brief #204.Search in Google Scholar
6. Marik, PE, Taeb, AM. SIRS, qSOFA and new sepsis definition. J Thorac Dis 2017;9:943–5. https://doi.org/10.21037/jtd.2017.03.125.Search in Google Scholar PubMed PubMed Central
7. Lippi, G, Montagnana, M, Balboni, F, Bellone, A, Casagranda, I, Cavazza, M, et al.. Academy of Emergency Medicine and Care-Society of Clinical Biochemistry and Clinical Molecular Biology consensus recommendations for clinical use of sepsis biomarkers in the emergency department. Emerg Care J 2017;13:6877. https://doi.org/10.4081/ecj.2017.6877.Search in Google Scholar
8. Sinha, M, Jupe, J, Mack, H, Coleman, TP, Lawrence, SM, Fraley, SI. Emerging technologies for molecular diagnosis of sepsis. Clin Microbiol Rev 2018;31. https://doi.org/10.1128/CMR.00089-17.Search in Google Scholar PubMed PubMed Central
9. Yang, HS, Hur, M, Yi, A, Kim, H, Lee, S, Kim, SN. Prognostic value of presepsin in adult patients with sepsis: systematic review and meta-analysis. PLoS One 2018;13:e0191486. https://doi.org/10.1371/journal.pone.0191486.Search in Google Scholar PubMed PubMed Central
10. Bartoletti, M, Antonelli, M, Bruno Blasi, FA, Casagranda, I, Chieregato, A, Fumagalli, R, et al.. Procalcitonin-guided antibiotic therapy: an expert consensus. Clin Chem Lab Med 2018;56:1223–9. https://doi.org/10.1515/cclm-2018-0259.Search in Google Scholar PubMed
11. Formenti, P, Gotti, M, Palmieri, F, Pastori, S, Roccaforte, V, Menozzi, A, et al.. Presepsin in critical illness: current knowledge and future perspectives. Diagnostics 2024;14:1311. https://doi.org/10.3390/diagnostics14121311.Search in Google Scholar PubMed PubMed Central
12. Eidizadeh, A, Asif, AR, von Ahsen, N, Binder, L, Schnelle, M. Differences in procalcitonin measurements between three BRAHMS-partnered immunoassays (Liaison, Elecsys and Architect). Clin Chem Lab Med 2019;57:e207–10. https://doi.org/10.1515/cclm-2018-0916.Search in Google Scholar PubMed
13. Buoro, S, Seghezzi, M, Vavassori, M, Dominoni, P, Apassiti Esposito, S, Manenti, B, et al.. Clinical significance of cell population data (CPD) on Sysmex XN-9000 in septic patients with our without liver impairment. Ann Transl Med 2016;4:418. https://doi.org/10.21037/atm.2016.10.73.Search in Google Scholar PubMed PubMed Central
14. Urrechaga, E, Bóveda, O, Aguirre, U. Role of leucocytes cell population data in the early detection of sepsis. J Clin Pathol 2018;71:259–66. https://doi.org/10.1136/jclinpath-2017-204524 [Epub 2017 Aug 18].Search in Google Scholar PubMed
15. Finazzi, S, Paci, G, Antiga, L, Brissy, O, Carrara, G, Crespi, D, et al.. PROSAFE: a European endeavor to improve quality of critical care medicine in seven countries. Minerva Anestesiol 2020;86:1305–20. https://doi.org/10.23736/s0375-9393.20.14112-9.Search in Google Scholar
16. de Grooth, H-J, Geenen, IL, Girbes, AR, Vincent, J-L, Parienti, J-J, Oudemans-van Straaten, HM. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care 2017;21:38. https://doi.org/10.1186/s13054-017-1609-1.Search in Google Scholar PubMed PubMed Central
17. Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012;120:c179–84. https://doi.org/10.1159/000339789.Search in Google Scholar PubMed
18. Martin, P, Awan, AA, Berenguer, MC, Bruchfeld, A, Fabrizi, F, Goldberg, DS, et al.. Executive summary of the KDIGO 2022 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int 2022;102:1228–37. https://doi.org/10.1016/j.kint.2022.07.012.Search in Google Scholar PubMed
19. Daves, M, Roccaforte, V, Lombardi, F, Panella, R, Pastori, S, Spreafico, M, et al.. Modern hematology analyzers: beyond the simple blood cells count (with focus on the red blood cells). J Lab Precis Med 2023;23–32. https://doi.org/10.21037/jlpm-23-32.Search in Google Scholar
20. Mandrekar, JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol 2010;5:1315–16. https://doi.org/10.1097/jto.0b013e3181ec173d.Search in Google Scholar PubMed
21. Linssen, J, Aderhold, S, Nierhaus, A, Frings, D, Kaltschmidt, C, Zänker, K. Automation and validation of a rapid method to assess neutrophil and monocyte activation by routine fluorescence flow cytometry in vitro. Cytometry B Clin Cytom 2008;74:295–309. https://doi.org/10.1002/cyto.b.20422.Search in Google Scholar PubMed
22. Klebanoff, SJ. Myeloperoxidase: friend and foe. J Leukoc Biol 2005;77:598–625. https://doi.org/10.1189/jlb.1204697.Search in Google Scholar PubMed
23. Formenti, P, Isidori, L, Pastori, S, Roccaforte, V, Mantovani, EA, Iezzi, M, et al.. A secondary retrospective analysis of the predictive value of neutrophil-reactive intensity (NEUT-RI) in septic and non-septic patients in intensive care. Diagnostics 2024;14:821. https://doi.org/10.3390/diagnostics14080821.Search in Google Scholar PubMed PubMed Central
24. Mantovani, EA, Formenti, P, Pastori, S, Roccaforte, V, Gotti, M, Panella, R, et al.. The potential role of neutrophil-reactive intensity (NEUT-RI) in the diagnosis of sepsis in critically ill patients: a retrospective cohort study. Diagnostics 2023;13:1781. https://doi.org/10.3390/diagnostics13101781.Search in Google Scholar PubMed PubMed Central
25. Buoro, S, Manenti, B, Seghezzi, M, Dominoni, P, Barbui, T, Ghirardi, A, et al.. Innovative haematological parameters for early diagnosis of sepsis in adult patients admitted in intensive care unit. J Clin Pathol 2018;71:330–5. https://doi.org/10.1136/jclinpath-2017-204643 [Epub 2017 Aug 20].Search in Google Scholar PubMed
26. Razeghi, E, Parkhideh, S, Ahmadi, F, Khashayar, P. Serum CRP levels in pre-dialysis patients. Ren Fail 2008;30:193–8. https://doi.org/10.1080/08860220701810539.Search in Google Scholar PubMed
27. Park, JH, Kim, DH, Jang, HR, Kim, M-J, Jung, SH, Lee, JE, et al.. Clinical relevance of procalcitonin and C-reactive protein as infection markers in renal impairment: a cross-sectional study. Crit Care 2014;18:640. https://doi.org/10.1186/s13054-014-0640-8.Search in Google Scholar PubMed PubMed Central
28. Han, S, Kim, MJ, Ko, HJ, Lee, EJ, Kim, HR, Jeon, JW, et al.. Diagnostic and prognostic roles of C-reactive protein, procalcitonin, and presepsin in acute kidney injury patients initiating continuous renal replacement therapy. Diagnostics 2023;13:777. https://doi.org/10.3390/diagnostics13040777.Search in Google Scholar PubMed PubMed Central
29. Zhang, W, Zhang, Z, Pan, S, Li, J, Yang, Y, Qi, H, et al.. The clinical value of hematological neutrophil and monocyte parameters in the diagnosis and identification of sepsis. Ann Transl Med 2021;9:1680. https://doi.org/10.21037/atm-21-5639.Search in Google Scholar PubMed PubMed Central
30. Lee, J, Gu, J, Seo, JE, Kim, JW, Kim, HK. Diagnostic and prognostic values of neutrophil Reactivity intensity (NEUT-RI) in pediatric systemic inflammatory response syndrome and sepsis. Ann Clin Lab Sci 2023;53:173–80.Search in Google Scholar
31. Agnello, L, Bivona, G, Vidali, M, Scazzone, C, Giglio, RV, Iacolino, G, et al.. Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department. Clin Chem Lab Med 2020;58:1951–7. https://doi.org/10.1515/cclm-2020-0417.Search in Google Scholar PubMed
32. Vivas, MC, Villamarin Guerrero, HF, Tascon, AJ, Valderrama-Aguirre, A. Plasma interleukin-6 levels correlate with survival in patients with bacterial sepsis and septic shock. Intervent Med Appl Sci 2021;11:224–30. https://doi.org/10.1556/1646.2020.00006.Search in Google Scholar PubMed PubMed Central
© 2024 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
- Reviews
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
- Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part V – Benefits for stakeholders other than participants
- Opinion Papers
- Not all biases are created equal: how to deal with bias on laboratory measurements
- Krebs von den Lungen-6 (KL-6) as a diagnostic and prognostic biomarker for non-neoplastic lung diseases
- General Clinical Chemistry and Laboratory Medicine
- Evaluation of performance in preanalytical phase EQA: can laboratories mitigate common pitfalls?
- Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR)
- The different serum albumin assays influence calcium status in haemodialysis patients: a comparative study against free calcium as a reference method
- Measurement of 1,25-dihydroxyvitamin D in serum by LC-MS/MS compared to immunoassay reveals inconsistent agreement in paediatric samples
- Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers
- Quality indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?
- Reference Values and Biological Variations
- Biological variation of cardiac biomarkers in athletes during an entire sport season
- Increased specificity of the “GFAP/UCH-L1” mTBI rule-out test by age dependent cut-offs
- Cancer Diagnostics
- An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
- Cardiovascular Diseases
- Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
- Infectious Diseases
- The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
- Letters to the Editor
- Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
- Does blood tube filling influence the Athlete Biological Passport variables?
- Influence of data visualisations on laboratorians’ acceptance of method comparison studies
- An appeal for biological variation estimates in deep immunophenotyping
- Serum free light chains reference intervals for the Lebanese population
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Articles in the same Issue
- Frontmatter
- Editorial
- Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
- Reviews
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
- Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories
- Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part V – Benefits for stakeholders other than participants
- Opinion Papers
- Not all biases are created equal: how to deal with bias on laboratory measurements
- Krebs von den Lungen-6 (KL-6) as a diagnostic and prognostic biomarker for non-neoplastic lung diseases
- General Clinical Chemistry and Laboratory Medicine
- Evaluation of performance in preanalytical phase EQA: can laboratories mitigate common pitfalls?
- Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR)
- The different serum albumin assays influence calcium status in haemodialysis patients: a comparative study against free calcium as a reference method
- Measurement of 1,25-dihydroxyvitamin D in serum by LC-MS/MS compared to immunoassay reveals inconsistent agreement in paediatric samples
- Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers
- Quality indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?
- Reference Values and Biological Variations
- Biological variation of cardiac biomarkers in athletes during an entire sport season
- Increased specificity of the “GFAP/UCH-L1” mTBI rule-out test by age dependent cut-offs
- Cancer Diagnostics
- An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
- Cardiovascular Diseases
- Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
- Infectious Diseases
- The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
- Letters to the Editor
- Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
- Does blood tube filling influence the Athlete Biological Passport variables?
- Influence of data visualisations on laboratorians’ acceptance of method comparison studies
- An appeal for biological variation estimates in deep immunophenotyping
- Serum free light chains reference intervals for the Lebanese population
- Applying the likelihood ratio concept in external quality assessment for ANCA
- A promising new direct immunoassay for urinary free cortisol determination