{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:00:48Z","timestamp":1767765648969,"version":"3.48.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Acute pancreatitis (AP) has a wide range of clinical severity, and early prediction of disease progression is still challenging. Trypsinogen-activating peptide (TAP) and trypsin-2 serve as direct biomarkers for intrapancreatic proteolytic activation and may provide earlier pathophysiological information compared with traditional markers. Materials and Methods: In this retrospective cohort analysis involving 54 AP patients, we evaluated 24 h serum and urinary TAP and trypsin-2 concentrations by Bayesian correlation, mediation analysis, unsupervised K-means clustering, and supervised machine learning (Elastic Net and Random Forest). The analyses investigated the relationships of biomarkers with inflammation (CRP), enzymatic activities (amylase, lipase), and clinical factors, as well as inflammation severity (CRP levels). Results: Bayesian correlations indicated moderate evidence for a relationship between serum TAP and CRP (BF10 = 8.42), as well as strong evidence linking age to serum TAP (BF10 = 12.75). Serum trypsin-2 showed no correlation with CRP, while urinary trypsin-2 had a correlation with amylase (BF10 = 6.89). Mediation analysis indicated that TAP and trypsin-2 accounted for 42\u201344% of the impact of CRP on pancreatic enzyme elevation. Clustering revealed three phenotypic subgroups (\u201cMild Activation\u201d, \u201cModerate System\u201d, and \u201cSevere Pancreatic-Renal\u201d), the latter showing the highest levels of CRP and biomarkers. Machine learning models highlighted urinary trypsin-2 and age as the most significant predictors of inflammation, with Random Forest achieving the highest performance (R2 = 0.53). Conclusions: Early urinary trypsin-2 outperforms serum markers as a predictor of systemic inflammatory intensity, indicating total proteolytic impairment and renal clearance. This integrative analysis reveals unique biological phenotypes and highlights the potential of these biomarkers for early assessment of the inflammatory burden. Their role in predicting clinical disease progression requires prospective validation. Integrative biomarker analysis reveals unique biological phenotypes and improves assessment of inflammatory burden in PA. Larger cohorts are required for prospective validation to incorporate these biomarkers into precision-based diagnostic frameworks.<\/jats:p>","DOI":"10.3390\/medicina62010116","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Bayesian Inference and Machine Learning to Evaluate TAP and Trypsin-2 as Early Biomarkers of Systemic Inflammation in Acute Pancreatitis"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4586-4795","authenticated-orcid":false,"given":"Alina","family":"Calin Frij","sequence":"first","affiliation":[{"name":"Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Surgery I, Sf. Spiridon Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Velicescu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Surgery I, Sf. Spiridon Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Andone","sequence":"additional","affiliation":[{"name":"Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7386-0859","authenticated-orcid":false,"given":"Roxana","family":"Covali","sequence":"additional","affiliation":[{"name":"Department of Radiology, Biomedical Engineering Faculty, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2079-2383","authenticated-orcid":false,"given":"Alin","family":"Ciubotaru","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Grigorovici","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sf. Spiridon Hospital, 700111 Iasi, Romania"},{"name":"Department of Doctoral Study, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Popa","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0732-3745","authenticated-orcid":false,"given":"Daniela","family":"Cosntantinescu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2802-5993","authenticated-orcid":false,"given":"Mariana","family":"Pavel-Tanasa","sequence":"additional","affiliation":[{"name":"Department of Immunology, Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-3991","authenticated-orcid":false,"given":"Alexandru","family":"Grigorovici","sequence":"additional","affiliation":[{"name":"Department of Surgery, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Department of Surgery I, Sf. Spiridon Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/gutjnl-2012-302779","article-title":"Classification of acute pancreatitis\u20142012: Revision of the Atlanta classification and definitions by international consensus","volume":"62","author":"Banks","year":"2013","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/ajg.2013.218","article-title":"American College of Gastroenterology guideline: Management of acute pancreatitis","volume":"108","author":"Tenner","year":"2013","journal-title":"Am. J. 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