Are S100A7 protein and V-set and immunoglobulin domain–containing 4 specific and robust early markers of severe acute pancreatitis?

macrophages (Kupffer cells), suggesting hepatic involvement or systemic activation.5 Furthermore, VSIG4 characterizes tumor -associated macrophages and predicts poor prognosis in aggressive malignancies.6-8 Consequently, elevated levels of VSIG4 in SAP may reflect systemic stress or occult premalignant changes rather than exclusive acute inflammatory severity.Without noncancerous septic controls, the diagnostic precision remains uncertain.Third, therapeutic heterogeneity confounds the day 2 proteomic profiles.The authors reported robust proteomic divergence on day 2 postadmission.However, according to the data presented in Supplementary material, Table S1, 75% of the SAP patients received antibiotics, as compared with only 8.3% of the MAP patients (P = 0.004).Consequently, the observed signals on day 2 likely capture the metabolic response to antimicrobial intervention rather than the natural disease trajectory alone.We believe addressing these issues in future validation studies-specifically by including MSAP patients, appropriate disease control groups (for example, patients with nonpancreatitic sepsis or nonsevere AP with systemic inflammation), and adjusting for treatment exposurewill be essential to establish the role of S100A7 and VSIG4 as viable clinical tools.