Identifying novel acute pancreatitis sub-phenotypes using total serum calcium trajectories

Abstract

BackgroundAcute pancreatitis (AP) has heterogeneous clinical features, and identifying clinically relevant sub-phenotypes is useful. We aimed to identify novel sub-phenotypes in hospitalized AP patients using longitudinal total serum calcium (TSC) trajectories.MethodsAP patients had at least two TSC measurements during the first 24 h of hospitalization in the US-based critical care database (Medical Information Mart for Intensive Care-III (MIMIC-III) and MIMIC-IV were included. Group-based trajectory modeling was used to identify calcium trajectory phenotypes, and patient characteristics and treatment outcomes were compared between the phenotypes.ResultsA total of 4518 admissions were included in the analysis. Four TSC trajectory groups were identified: “Very low TSC, slow resolvers” (n = 65; 1.4% of the cohort); “Moderately low TSC” (n = 559; 12.4%); “Stable normal-calcium” (n = 3875; 85.8%); and “Fluctuating high TSC” (n = 19; 0.4%). The “Very low TSC, slow resolvers” had the lowest initial, maximum, minimum, and mean TSC, and highest SOFA score, creatinine and glucose level. In contrast, the “Stable normal-calcium” had the fewest ICU admission, antibiotic use, intubation and renal replace treatment. In adjusted analysis, significantly higher in-hospital mortality was noted among “Very low TSC, slow resolvers” (odds ratio [OR], 7.2; 95% CI, 3.7 to 14.0), “moderately low TSC” (OR, 5.0; 95% CI, 3.8 to 6.7), and “Fluctuating high TSC” (OR, 5.6; 95% CI, 1.5 to 20.6) compared with the “Stable normal-calcium” group.ConclusionsWe identified four novel sub-phenotypes of patients with AP, with significant variability in clinical outcomes. Not only the absolute TSC levels but also their trajectories were significantly associated with in-hospital mortality.