Validation of AIA-360 for Determination of Presepsin: A Useful Tool for the Diagnosis of Sepsis at the Emergency Department
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Instrument Characteristics
2.3. Precision Study
2.4. Linearity Assessment
2.5. Carryover
2.6. Repeatability
2.7. Statistical Analysis
3. Results
3.1. Discrimination Among Study Groups
3.2. Validation of AIA-360 Instrument
3.3. ROC Analysis of Presepsin: Diagnostic Role as Sepsis Biomarker
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Geroulanos, S.; Douka, E.T. Historical perspective of the word “sepsis”. Intensive Care Med. 2006, 32, 2077. [Google Scholar] [CrossRef] [PubMed]
- Singer, M.; Deutschman, C.S.; Seymour, C.W.; Shankar-Hari, M.; Annane, D.; Bauer, M.; Bellomo, R.; Bernard, G.R.; Chiche, J.-D.; Coopersmith, C.M.; et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016, 315, 801–810. [Google Scholar] [CrossRef]
- Memar, M.Y.; Baghi, H.B. Presepsin: A promising biomarker for the detection of bacterial infections. Biomed. Pharmacother. 2019, 111, 649–656. [Google Scholar] [CrossRef]
- Piccioni, A.; Santoro, M.C.; de Cunzo, T.; Tullo, G.; Cicchinelli, S.; Saviano, A.; Valletta, F.; Pascale, M.M.; Candelli, M.; Covino, M.; et al. Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review. Medicina 2021, 57, 770. [Google Scholar] [CrossRef]
- Kim, H.I.; Park, S. Sepsis: Early Recognition and Optimized Treatment. Tuberc. Respir. Dis. 2019, 82, 6–14. [Google Scholar] [CrossRef]
- Fleischmann, M.C.; Scherag, A.; Adhikari, N.K.J.; Hartog, C.S.; Tsaganos, T.; Schlattmann, P.; Angus, D.C.; Reinhart, K. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am. J. Respir. Crit. Care Med. 2016, 193, 259–272. [Google Scholar] [CrossRef] [PubMed]
- Sinha, M.; Jupe, J.; Mack, H.; Coleman, T.P.; Lawrence, S.M.; Fraley, S.I. Emerging Technologies for Molecular Diagnosis of Sepsis. Clin. Microbiol. Rev. 2018, 31, e00089-17. [Google Scholar] [CrossRef]
- Lin, G.-L.; McGinley, J.P.; Drysdale, S.B.; Pollard, A.J. Epidemiology and Immune Pathogenesis of Viral Sepsis. Front. Immunol. 2018, 9, 2147. [Google Scholar] [CrossRef] [PubMed]
- Pieri, M.; Ciotti, M.; Nuccetelli, M.; Perrone, M.A.; Caliò, M.T.; Lia, M.S.; Minieri, M.; Bernardini, S. Serum Amyloid A Protein as a useful biomarker to predict COVID-19 patients severity and prognosis. Int. Immunopharmacol. 2021, 95, 107512. [Google Scholar] [CrossRef]
- Gavelli, F.; Castello, L.M.; Avanzi, G.C. Management of sepsis and septic shock in the emergency department. Intern. Emerg. Med. 2021, 16, 1649–1661. [Google Scholar] [CrossRef] [PubMed]
- Spoto, S.; Cella, E.; de Cesaris, M.; Locorriere, L.; Mazzaroppi, S.; Nobile, E.; Lanotte, A.M.; Pedicino, L.; Fogolari, M.; Costantino, S.; et al. Procalcitonin and MR-Proadrenomedullin Combination with SOFA and qSOFA Scores for Sepsis Diagnosis and Prognosis: A Diagnostic Algorithm. Shock 2018, 50, 44–52. [Google Scholar] [CrossRef]
- Piano, S.; Bartoletti, M.; Tonon, M.; Baldassarre, M.; Chies, G.; Romano, A.; Viale, P.; Vettore, E.; Domenicali, M.; Stanco, M.; et al. Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections. Gut 2018, 67, 1892–1899. [Google Scholar] [CrossRef]
- Sinha, M.; Desai, S.; Mantri, S.; Kulkarni, A. Procalcitonin as an adjunctive biomarker in sepsis. Indian J. Anaesth. 2011, 55, 266–270. [Google Scholar] [CrossRef]
- Park, J.; Yoon, J.H.; Ki, H.K.; Ko, J.-H.; Moon, H.-W. Performance of presepsin and procalcitonin predicting culture-proven bacterial infection and 28-day mortality: A cross sectional study. Front. Med. 2022, 9, 954114. [Google Scholar] [CrossRef]
- Largman-Chalamish, M.; Wasserman, A.; Silberman, A.; Levinson, T.; Ritter, O.; Berliner, S.; Zeltser, D.; Shapira, I.; Rogowski, O.; Shenhar-Tsarfaty, S. Differentiating between bacterial and viral infections by estimated CRP velocity. PLoS ONE 2022, 17, e0277401. [Google Scholar] [CrossRef] [PubMed]
- Covington, E.W.; Roberts, M.Z.; Dong, J. Procalcitonin Monitoring as a Guide for Antimicrobial Therapy: A Review of Current Literature. Pharmacotherapy 2018, 38, 569–581. [Google Scholar] [CrossRef]
- Riedel, S.; Melendez, J.H.; An, A.T.; Rosenbaum, J.E.; Zenilman, J.M. Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am. J. Clin. Pathol. 2011, 135, 182–189. [Google Scholar] [CrossRef] [PubMed]
- Pradhan, S.; Ghimire, A.; Bhattarai, B.; Khanal, B.; Pokharel, K.; Lamsal, M.; Koirala, S. The role of C-reactive protein as a diagnostic predictor of sepsis in a multidisciplinary Intensive Care Unit of a tertiary care center in Nepal. Indian J. Crit. Care Med. 2016, 20, 417–420. [Google Scholar] [CrossRef]
- Ryoo, S.M.; Han, K.S.; Ahn, S.; Shin, T.G.; Hwang, S.Y.; Chung, S.P.; Hwang, Y.J.; Park, Y.S.; Jo, Y.H.; Chang, H.L.; et al. The usefulness of C-reactive protein and procalcitonin to predict prognosis in septic shock patients: A multicenter prospective registry-based observational study. Sci. Rep. 2019, 9, 6579. [Google Scholar] [CrossRef]
- Minieri, M.; Di Lecce, V.N.; Lia, M.S.; Maurici, M.; Leonardis, F.; Longo, S.; Colangeli, L.; Paganelli, C.; Levantesi, S.; Terrinoni, A.; et al. Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department. Diagnostics 2022, 12, 1971. [Google Scholar] [CrossRef]
- Minieri, M.; Di Lecce, V.N.; Lia, M.S.; Maurici, M.; Bernardini, S.; Legramante, J.M. Role of MR-proADM in the risk stratification of COVID-19 patients assessed at the triage of the Emergency Department. Crit. Care 2021, 25, 407. [Google Scholar] [CrossRef]
- Spoto, S.; Legramante, J.M.; Minieri, M.; Fogolari, M.; Terrinoni, A.; Valeriani, E.; Sebastiano, C.; Bernardini, S.; Ciccozzi, M.; Angeletti, S. How biomarkers can improve pneumonia diagnosis and prognosis: Procalcitonin and mid-regional-pro-adrenomedullin. Biomark Med. 2020, 14, 549–562. [Google Scholar] [CrossRef]
- Maddaloni, C.; De Rose, D.U.; Santisi, A.; Martini, L.; Caoci, S.; Bersani, I.; Ronchetti, M.P.; Auriti, C. The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. Int. J. Mol. Sci. 2021, 22, 12154. [Google Scholar] [CrossRef]
- Velissaris, D.; Zareifopoulos, N.; Lagadinou, M.; Platanaki, C.; Tsiotsios, K.; Stavridis, E.L.; Kasartzian, D.; Pierrakos, C.; Karamouzos, V. Procalcitonin and sepsis in the Emergency Department: An update. Eur. Rev. Med. Pharmacol. Sci. 2021, 25, 466–479. [Google Scholar]
- Dugar, S.; Choudhary, C.; Duggal, A. Sepsis and septic shock: Guideline-based management. Clevel. Clin. J. Med. 2020, 87, 53–64. [Google Scholar] [CrossRef] [PubMed]
- Rahmel, T. SSC International Guideline 2016—Management of Sepsis and Septic Shock. Anasthesiol. Intensiv. Notfallmed. Schmerzther. 2018, 53, 142–148. [Google Scholar]
- Shakoor, M.; Dar, R.; Javed, K. Diagnostic Accuracy of Serum Presepsin as Biomarker of Bacterial Sepsis in Paediatric Patients. J. Coll. Physicians Surg. Pak. 2023, 33, 1288–1292. [Google Scholar] [PubMed]
- Pietrasanta, C.; Ronchi, A.; Vener, C.; Poggi, C.; Ballerini, C.; Testa, L.; Colombo, R.M.; Spada, E.; Dani, C.; Mosca, F.; et al. Presepsin (Soluble CD14 Subtype) as an Early Marker of Neonatal Sepsis and Septic Shock: A Prospective Diagnostic Trial. Antibiotics 2021, 10, 580. [Google Scholar] [CrossRef] [PubMed]
- Ulla, M.; Pizzolato, E.; Lucchiari, M.; Loiacono, M.; Soardo, F.; Forno, D.; Morello, F.; Lupia, E.; Moiraghi, C.; Mengozzi, G.; et al. Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: A multicenter prospective study. Crit. Care 2013, 17, R168. [Google Scholar] [CrossRef] [PubMed]
- Wei, S.; Shen, Z.; Yin, Y.; Cong, Z.; Zeng, Z.; Zhu, X. Advances of presepsin in sepsis-associated ARDS. Postgrad. Med. J. 2024, 100, 209–218. [Google Scholar] [CrossRef]
- Vidali, M.; Tronchin, M.; Dittadi, R. Protocol for the comparison of two laboratory methods. Biochim. Clin. 2016, 40, 129–142. [Google Scholar]
- Nahm, F.S. Receiver operating characteristic curve: Overview and practical use for clinicians. Korean J. Anesthesiol. 2022, 75, 25–36. [Google Scholar] [CrossRef] [PubMed]
- Shankar-Hari, M.; Phillips, G.S.; Levy, M.L.; Seymour, C.W.; Liu, V.X.; Deutschman, C.S.; Angus, D.C.; Rubenfeld, G.D.; Singer, M. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016, 315, 775–787. [Google Scholar] [CrossRef]
- Enguix-Armada, A.; Escobar-Conesa, R.; García-De La Torre, A.; De La Torre-Prados, M.V. Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin. Clin. Chem. Lab. Med. 2016, 54, 163–168. [Google Scholar] [CrossRef]
- Angeletti, S.; Battistoni, F.; Fioravanti, M.; Bernardini, S.; Dicuonzo, G. Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis. Clin. Chem. Lab. Med. 2013, 51, 1059–1067. [Google Scholar] [CrossRef] [PubMed]
- Póvoa, P.; Coelho, L.; Dal-Pizzol, F.; Ferrer, R.; Huttner, A.; Morris, A.C.; Nobre, V.; Ramirez, P.; Rouze, A.; Salluh, J.; et al. How to use biomarkers of infection or sepsis at the bedside: Guide to clinicians. Intensive Care Med. 2023, 49, 142–153. [Google Scholar] [CrossRef]
- Bennett, S.R. Sepsis in the intensive care unit. Surgery 2015, 33, 565–571. [Google Scholar]
- de Guadiana Romualdo, L.G.; Torrella, P.E.; Acebes, S.R.; Otón, M.D.A.; Sánchez, R.J.; Holgado, A.H.; Santos, E.J.; Freire, A.O. Diagnostic accuracy of presepsin (sCD14-ST) as a biomarker of infection and sepsis in the emergency department. Clin. Chim. Acta 2017, 464, 6–11. [Google Scholar] [CrossRef]
- Behnes, M.; Bertsch, T.; Lepiorz, D.; Lang, S.; Trinkmann, F.; Brueckmann, M.; Borggrefe, M.; Hoffmann, U. Diagnostic and prognostic utility of soluble CD 14 subtype (presepsin) for severe sepsis and septic shock during the first week of intensive care treatment. Crit. Care 2014, 18, 507. [Google Scholar] [CrossRef] [PubMed]
- Guirgis, F.; Black, L.P.; DeVos, E.L. Updates and controversies in the early management of sepsis and septic shock. Emerg. Med. Pract. 2018, 20, 1–28. [Google Scholar]
- Agnello, L.; Giglio, R.V.; Bivona, G.; Scazzone, C.; Gambino, C.M.; Iacona, A.; Ciaccio, A.M.; Sasso, B.L.; Ciaccio, M. The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis. Diagnostics 2021, 11, 1881. [Google Scholar] [CrossRef] [PubMed]
- Levy, M.M.; Evans, L.E.; Rhodes, A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensiv. Care Med. 2018, 44, 925–928. [Google Scholar] [CrossRef] [PubMed]
GROUP 0 | GROUP 1 | GROUP 2 | |
---|---|---|---|
SAMPLES | 38 | 44 | 15 |
BIOLOGICAL SEX | MALE: 30 | MALE: 23 | MALE: 10 |
FEMALE: 8 | FEMALE: 21 | FEMALE: 5 | |
HOSPITAL UNIT | TRANSFUSION DEPT | EMERGENCY DEPT | EMERGENCY DEPT |
CLINICAL SIGNS | NONE, GOOD HEALTH | FEVER | FEVER, TACHYPNEA, ALTERATION OF CONSCIOUSNESS STATE, HYPOTENSION |
PROCALCITONIN | <0.01 | 77% NEG; 23% POS 0.36 (IQR 0.16 to 0.72) | 100% POS 6.0 (IQR 1.31 to 14.32) |
C-REACTIVE PROTEIN | <1.00 | 93% POS; 7% NEG 61.6 (IQR: 39.75 to 103.92) | 100% POS 140.8 (IQR: 81.75 to 221.37) |
SARS-CoV-2 RT-PCR SWAB | NEG | NEG | NEG |
BLOOD CULTURE | N/A | NEG | POS |
SEPSIS DIAGNOSIS | N/A | NEG | POS |
Within-Run | Between-Run | Total Precision | ||||
---|---|---|---|---|---|---|
CV% Manufacturer | CV% Laboratory | CV% Manufacturer | CV% Laboratory | CV% Manufacturer | CV% Laboratory | |
ICQ Level 1 | / | 3.5 | 3.8 | 3.8 | 4.5 | 4.8 |
ICQ Level 2 | / | 2.7 | 4.5 | 1.8 | 4.5 | 2.8 |
Presepsin pg/mL | Diagnosis |
---|---|
<200 pg/mL | Sepsis excluded (Negative Predictive Value, NPV = 98%) |
<300 pg/mL | Systemic infection is not probable |
<600 pg/mL | Systemic infection (sepsis) is possible |
<1000 pg/mL | Significant risk of progression of systemic infection (sepsis), increased risk of unfavorable outcome |
>1000 pg/mL | High risk of progression of systemic infection (sepsis, septic shock); high risk of 30-day mortality comparable to SOFA score ≥ 8 |
CARRYOVER | pg/mL |
---|---|
HIGH–LOW Media | 172.784 |
Minimum Concentration | 167.545 |
Maximum Concentration | 4935.995 |
LOW–LOW media | 174.25 |
Carryover effect | −1.4662 |
Error Limit | 15.40710327 |
Samples | Media (pg/mL) | SD | CV% |
---|---|---|---|
Normal | 386.44 | 14.84 | 4 |
Pathological | 2679.64 | 80.27 | 3 |
Presepsin (pg/mL) | n | Minimum | 25th Percentile | Median (pg/mL) | 75th Percentile | Maximum |
---|---|---|---|---|---|---|
Control group (0) | 38 | 84.30 | 345.35 | 473.90 * | 598.82 | 1066.70 |
Non-septic inflammatory condition group (1) | 44 | 283.60 | 633.95 | 874.40 * | 1171.55 | 5112.20 |
Confirmed sepsis group (2) | 15 | 314.70 | 1164.20 | 1467.10 * | 2782.10 | 16,272.20 |
Biomarker | AUC | Cut-Off Level | Sensitivity (%) (CI 95%) | Specificity (%) (CI 95%) | LR (+) (CI 95%) | LR (−) (CI 95%) |
---|---|---|---|---|---|---|
Presepsin (pg/mL) | 0.876 (CI: 0.705 to 0.934) | 890 a | 93.33 (68.1−99.8) | 76.19 (65.7−84.8) | 3.92 (2.6−5.9) | 0.088 (0.01−0.6) |
Procalcitonin (ng/mL) | 0.926 (CI: 0.813 to 0.982) | 0.5 | 100 (78.2−100) | 69.70 (51.3−84.4) | 3.30 (2−5.5) | 0 |
C-Reactive Protein (mg/L) | 0.718 (CI: 0.579 to 0.832) | 97.7 | 73.33 (44.9−92.2) | 74.36 (57.9−87) | 2.86 (1.5−5.3) | 0.36 (0.2−0.8) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Giovannelli, A.; Pieri, M.; Nicolai, E.; Pelagalli, M.; Calabrese, C.; Tomassetti, F.; Legramante, J.M.; Terrinoni, A.; Bernardini, S.; Minieri, M. Validation of AIA-360 for Determination of Presepsin: A Useful Tool for the Diagnosis of Sepsis at the Emergency Department. LabMed 2025, 2, 1. https://doi.org/10.3390/labmed2010001
Giovannelli A, Pieri M, Nicolai E, Pelagalli M, Calabrese C, Tomassetti F, Legramante JM, Terrinoni A, Bernardini S, Minieri M. Validation of AIA-360 for Determination of Presepsin: A Useful Tool for the Diagnosis of Sepsis at the Emergency Department. LabMed. 2025; 2(1):1. https://doi.org/10.3390/labmed2010001
Chicago/Turabian StyleGiovannelli, Alfredo, Massimo Pieri, Eleonora Nicolai, Martina Pelagalli, Cinzia Calabrese, Flaminia Tomassetti, Jacopo Maria Legramante, Alessandro Terrinoni, Sergio Bernardini, and Marilena Minieri. 2025. "Validation of AIA-360 for Determination of Presepsin: A Useful Tool for the Diagnosis of Sepsis at the Emergency Department" LabMed 2, no. 1: 1. https://doi.org/10.3390/labmed2010001
APA StyleGiovannelli, A., Pieri, M., Nicolai, E., Pelagalli, M., Calabrese, C., Tomassetti, F., Legramante, J. M., Terrinoni, A., Bernardini, S., & Minieri, M. (2025). Validation of AIA-360 for Determination of Presepsin: A Useful Tool for the Diagnosis of Sepsis at the Emergency Department. LabMed, 2(1), 1. https://doi.org/10.3390/labmed2010001