{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:09:31Z","timestamp":1779887371482,"version":"3.53.1"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Healthcare-associated infections remain a major cause of morbidity and mortality in paediatric patients, particularly among those undergoing surgery or requiring intensive care. Distinguishing postoperative sterile inflammation from early sepsis is clinically challenging because conventional biomarkers such as C-reactive protein (CRP) and procalcitonin lack sufficient specificity. This narrative review aimed to analyse current evidence on pancreatic stone protein (PSP) as an emerging biomarker for the detection and risk stratification of infection in paediatric populations. A structured literature search was performed in PubMed and Web of Science for studies published between 2020 and 2026 using terms related to nosocomial infections, paediatric surgery, and PSP, identifying 147 articles; 54 met the inclusion criteria after screening. The analysed studies show that PSP levels increase significantly in children with sepsis compared with those with non-infectious systemic inflammation and are associated with bacteraemia, organ dysfunction, and mortality. In several paediatric cohorts, PSP demonstrated diagnostic performance comparable to or better than traditional markers, with reported AUROC values up to approximately 0.82 for distinguishing sepsis from non-infectious inflammation. Evidence from neonatal and high-risk populations also suggests strong sensitivity and specificity for early infection detection. Overall, PSP appears to be a promising biomarker for the early identification and prognostic stratification of paediatric sepsis; however, variability among studies highlights the need for larger multicentre prospective investigations and for integrating PSP into multimarker diagnostic algorithms.<\/jats:p>","DOI":"10.3390\/ijms27114827","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"4827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pancreatic Stone Protein as an Emerging Biomarker in Paediatric Nosocomial and Postoperative Sepsis: An Integrative Review of Diagnostic and Prognostic Performance"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2885-0683","authenticated-orcid":false,"given":"Adrian","family":"Ram\u00edrez Quintana","sequence":"first","affiliation":[{"name":"Department of Fundamental, Prophylactic and Clinical Disciplines, Faculty of Medicine, Transilvania University of Brasov, 56 Nicolae Balcescu, 500019 Brasov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Laura","family":"Gaman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bdul Eroilor Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4824-2175","authenticated-orcid":false,"given":"Mihaela","family":"Badea","sequence":"additional","affiliation":[{"name":"Department of Fundamental, Prophylactic and Clinical Disciplines, Faculty of Medicine, Transilvania University of Brasov, 56 Nicolae Balcescu, 500019 Brasov, Romania"},{"name":"Research Center for Fundamental Research and Prevention Strategies in Medicine, Research and Development Institute, Transilvania University of Brasov, 10 Institutului St., 500484 Brasov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Mihaela","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Department of Fundamental, Prophylactic and Clinical Disciplines, Faculty of Medicine, Transilvania University of Brasov, 56 Nicolae Balcescu, 500019 Brasov, Romania"},{"name":"Research Center for Fundamental Research and Prevention Strategies in Medicine, Research and Development Institute, Transilvania University of Brasov, 10 Institutului St., 500484 Brasov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41390-023-02499-0","article-title":"Pediatric sepsis diagnostic and prognostic biomarkers: Pancreatic stone protein, copeptin, and apolipoprotein A-V","volume":"94","author":"Saleh","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13052-023-01540-6","article-title":"Accuracy of Pancreatic Stone Protein for the diagnosis of sepsis in children admitted to paediatric intensive care or high-dependency care: A pilot study","volume":"49","author":"Bottari","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"154772","DOI":"10.1016\/j.jcrc.2024.154772","article-title":"Serial monitoring of pancreatic stone protein for the detection of sepsis in intensive care unit patients with complicated abdominal surgery: A prospective, longitudinal cohort study","volume":"82","author":"Filippidis","year":"2024","journal-title":"J. Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ventura, F., Eggimann, P., Daix, T., Fran\u00e7ois, B., and Pugin, J. (2023). Usefulness of pancreatic stone protein measurement to screen and diagnose sepsis in the context of the Surviving Sepsis Campaign recommendations. Med. Res. Arch., 11.","DOI":"10.18103\/mra.v11i12.4893"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1080\/1354750X.2025.2579636","article-title":"Pancreatic Stone Protein levels reflect sepsis severity and bloodstream infections in critically ill children: A retrospective cohort analysis","volume":"30","author":"Bottari","year":"2025","journal-title":"Biomarkers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1097\/PCC.0000000000003565","article-title":"Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Centre Prospective Cohort Study","volume":"25","author":"Bottari","year":"2024","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s13054-021-03609-2","article-title":"Accuracy of pancreatic stone protein for the diagnosis of infection in hospitalised adults: A systematic review and individual patient-level meta-analysis","volume":"25","author":"Prazak","year":"2021","journal-title":"Crit. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jped.2025.04.006","article-title":"Combining procalcitonin, C-reactive protein, and white blood cell count in predicting infections in paediatric open cardiac surgery with cardiopulmonary bypass","volume":"101","author":"Ha","year":"2025","journal-title":"J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Hond, T., Oosterheert, J., Van Hemert-Glaubitz, S., Musson, R., and Kaasjager, K. (2022). Pancreatic Stone Protein as a Biomarker for Sepsis at the Emergency Department of a Large Tertiary Hospital. Pathogens, 11.","DOI":"10.3390\/pathogens11050559"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00134-022-06769-z","article-title":"Presymptomatic diagnosis of postoperative infection and sepsis using gene expression signatures","volume":"48","author":"Lukaszewski","year":"2022","journal-title":"Intensive Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mai, B., Zhou, L., Wang, Q., Ding, B., Zhan, Y., Qin, S., Zhu, N., Li, Z., and Lei, Z. (2024). Diagnostic accuracy of pancreatic stone protein in patients with sepsis: A systematic review and meta-analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09347-4"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fidalgo, P., Nora, D., Coelho, L., and P\u00f3voa, P. (2022). Pancreatic Stone Protein: Review of a New Biomarker in Sepsis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11041085"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Arturi, F., Melegari, G., Mancano, R., Gazzotti, F., Bertellini, E., and Barbieri, A. (2025). Pancreatic Stone Protein as a Versatile Biomarker: Current Evidence and Clinical Applications. Diseases, 13.","DOI":"10.3390\/diseases13080240"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.21608\/azjp.2024.354185","article-title":"Role of Serum Pancreatic Stone Protein as a New Biomarker for Diagnosis of Late-Onset Neonatal Sepsis","volume":"27","author":"Fathi","year":"2024","journal-title":"Al-Azhar J. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, P., Xiao, Z., Lu, X., Zhang, X., and Huang, J. (2025). Pancreatic stone protein inhibits pyroptosis of pancreatic acinar cells in sepsis-associated pancreatic injury. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1566728"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ceccato, A., Camprub\u00ed-Rimblas, M., Bos, L., P\u00f3voa, P., Mart\u00edn-Loeches, I., Forn\u00e9, C., Areny-Balaguer\u00f3, A., Campa\u00f1a-Duel, E., Morales-Quinteros, L., and Quero, S. (2023). Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102676"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1007\/s15010-023-02093-w","article-title":"Discriminative performance of pancreatic stone protein in predicting ICU mortality and infection severity in adult patients with infection: A systematic review and individual patient level meta-analysis","volume":"51","author":"Zuercher","year":"2023","journal-title":"Infection"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2023065","DOI":"10.4084\/MJHID.2023.065","article-title":"Kinetics and Role of Pancreatic Stone Protein and Midregional Proadrenomedullin as Predictors of Sepsis and Bacteremia in Children with Hematological Malignancies","volume":"15","author":"Antari","year":"2023","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40635-024-00634-7","article-title":"Examining pancreatic stone protein response in ICU-acquired bloodstream infections: A matched event analysis","volume":"12","author":"Verlaan","year":"2024","journal-title":"Intensive Care Med. Exp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2147\/IDR.S457991","article-title":"Nosocomial Infections After Paediatric Congenital Heart Disease Surgery: Data from the National Centre for Cardiovascular Diseases in China","volume":"17","author":"Wang","year":"2024","journal-title":"Infect. Drug Resist."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jpedsurg.2022.09.019","article-title":"Association of dysglycaemia with post-operative outcomes in paediatric surgery","volume":"58","author":"Vanderhoek","year":"2023","journal-title":"J. Paediatr. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s10096-022-04502-8","article-title":"A longitudinal analysis of nosocomial bloodstream infections among preterm neonates","volume":"41","author":"Jansen","year":"2022","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hasan, M.S., Islam, N., and Mitul, A.R. (2022). Neonatal Surgical Morbidity and Mortality at a Single Tertiary Centre in a Low- and Middle-Income Country: A Retrospective Study of Clinical Outcomes. Front. Surg., 9.","DOI":"10.3389\/fsurg.2022.817528"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1055\/s-0040-1714256","article-title":"The Spanish National Network \u2018Grupo Castrillo\u2019: 22 Years of Nationwide Neonatal Infection Surveillance","volume":"37","year":"2020","journal-title":"Am. J. Perinatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"744","DOI":"10.55730\/1300-0144.5844","article-title":"Prognostic and diagnostic utility of pancreatic stone protein in paediatric sepsis and mortality","volume":"54","author":"Ceran","year":"2024","journal-title":"Turk. J. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1035856","DOI":"10.1155\/2016\/1035856","article-title":"The Role of Pancreatic Stone Protein in Diagnosis of Early Onset Neonatal Sepsis","volume":"2016","author":"Rass","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"489","DOI":"10.23736\/S0026-4946.16.04317-X","article-title":"The value of pancreatic stone protein in the prediction of infected neonates","volume":"69","author":"Wu","year":"2017","journal-title":"Minerva Paediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cyto.2014.01.009","article-title":"Pancreatic stone protein\u2014A possible biomarker of multiorgan failure and mortality in paediatric sepsis","volume":"66","author":"Fedora","year":"2014","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Schlapbach, L.J., Giannoni, E., Wellmann, S., Stocker, M., Ammann, R.A., and Graf, R. (2015). Normal values for pancreatic stone protein in different age groups. BMC Anesthesiol., 15.","DOI":"10.1186\/s12871-015-0149-y"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/jpen.2195","article-title":"Elimination of hospital-acquired central line-associated bloodstream infection on a mixed-service paediatric unit","volume":"46","author":"Mezoff","year":"2022","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.ajic.2020.02.011","article-title":"Routine scrubbing reduced central line-associated bloodstream infection in the NICU","volume":"48","author":"Oh","year":"2020","journal-title":"Am. J. Infect. Control"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13208","DOI":"10.1111\/tid.13208","article-title":"Bacterial infections in children after liver transplantation: A single-centre surveillance study of 345 consecutive transplants","volume":"22","author":"Guiddir","year":"2020","journal-title":"Transpl. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tural Kara, T., A\u00e7ik, A.K., Tekeli, O., and \u00c7a\u011flar Kizil, H.B. (2026). Clinical, Laboratory and Prognostic Features of Nosocomial Infections Caused by Carbapenemase-producing Klebsiella pneumoniae in Paediatric Patients. Pediatr. Infect. Dis. J.","DOI":"10.1097\/INF.0000000000005182"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/jgid.jgid_130_24","article-title":"Antimicrobial Resistance in Hospital-acquired Bloodstream Infections among Children in a Paediatric Hospital in Bolivia","volume":"17","author":"Rodriguez","year":"2025","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"326","DOI":"10.5144\/0256-4947.2025.326","article-title":"Epidemiology of paediatric Acinetobacter spp bacteraemia at a tertiary care centre in Riyadh, Saudi Arabia","volume":"45","author":"Gashgarey","year":"2025","journal-title":"Ann. Saudi Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Peng, X., Zhou, W., Zhu, Y., and Wan, C. (2021). Epidemiology, risk factors and outcomes of bloodstream infection caused by ESKAPEEc pathogens among hospitalised children. BMC Paediatr., 21.","DOI":"10.1186\/s12887-021-02661-9"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/bmjqs-2023-016831","article-title":"Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: A cross-sectional study","volume":"33","author":"Leekha","year":"2024","journal-title":"BMJ Qual. Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/jbcr\/irae111","article-title":"FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Paediatric Burn Injury","volume":"45","author":"Penatzer","year":"2024","journal-title":"J. Burn Care Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1203\/00006450-199410000-00022","article-title":"Developmental gene expression in the human foetal pancreas","volume":"36","author":"Mally","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.pan.2020.01.016","article-title":"Pancreatic stone protein\u2014Sepsis and the riddles of the exocrine pancreas","volume":"20","author":"Graf","year":"2020","journal-title":"Pancreatology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, Z., Downing, S., and Tzanakakis, E.S. (2019). Forty years of research on the Reg family: Still riddles?. Front. Cell Dev. Biol., 7.","DOI":"10.3389\/fcell.2019.00235"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1515\/bmc.2011.055","article-title":"Regenerating proteins and their expression, regulation and signalling","volume":"3","author":"Parikh","year":"2012","journal-title":"Biomol. Concepts"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"30162","DOI":"10.18632\/oncotarget.16282","article-title":"The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP\/regI and PAP\/regIII","volume":"8","author":"Reding","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/carcin\/bgm250","article-title":"REG I\u03b1 protein mediates an anti-apoptotic effect of STAT3 signalling in gastric cancer cells","volume":"29","author":"Sekikawa","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Calderari, S., Irminger, J.-C., Giroix, M.-H., Gangnerau, M.-N., Coulaud, J., Rickenbach, K., Gauguier, D., Halban, P., Serradas, P., and Homo-Delarche, F. (2014). Regenerating 1 protein is involved in the inflammatory response in islet beta-cells from Goto-Kakizaki diabetic rats with peri-islet macrophage infiltration and IL-6 secretion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090045"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1097\/CCM.0b013e31819da7d6","article-title":"Pancreatic stone protein is highly increased during post-traumatic sepsis and activates neutrophil granulocytes","volume":"37","author":"Keel","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2217\/bmm-2018-0194","article-title":"Measurement of pancreatic stone protein in the identification and management of sepsis","volume":"13","author":"Eggimann","year":"2019","journal-title":"Biomark. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1172\/JCI114762","article-title":"Enhanced expression of an exocrine pancreatic protein in Alzheimer\u2019s disease and the developing human brain","volume":"86","author":"Ozturk","year":"1990","journal-title":"J. Clin. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4827\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:42:13Z","timestamp":1779885733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114827"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114827","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}