Intracellular ATP Levels in CD4+ T Lymphocytes as a Prognostic Marker for 28-Day Mortality in Adult ICU Patients with Sepsis: A Retrospective Study.

OBJECTIVE: To systematically evaluate the prognostic significance of CD4⁺ T-cell intracellular adenosine triphosphate (iATP)-derived parameters in adult ICU patients with sepsis, and to explore whether integrating stimulated iATP (s-iATP) with the APACHE II score provides additional prognostic information for 28-day mortality prediction. METHODS: This single-center retrospective cohort study included adult ICU patients with sepsis admitted between May 2022 and March 2024. CD4⁺ T-cell iATP parameters, including s-iATP, non-stimulated iATP (n-iATP), the difference (s-n iATP), and the ratio (s/n iATP), were measured within 24 hours of sepsis diagnosis. Associations between iATP parameters and clinical outcomes, particularly 28-day mortality, were evaluated using survival and predictive analyses, and the prognostic value of combining s-iATP with the APACHE II score was assessed. RESULTS: A total of 131 patients were divided into high (n = 99) and low (n = 32) s-iATP groups based on the optimal cutoff value of 68 ng/mL. s-iATP showed a weak positive correlation with CD4⁺ T-cell count (r = 0.24). ROC analysis identified s-iATP as the best predictor of 28-day mortality (AUC = 0.760). Patients in the low s-iATP group had higher 28-day mortality, in-hospital mortality, progression to septic shock, and development of MODS among those without MODS at admission. After adjustment for confounders, low s-iATP remained independently associated with increased 28-day mortality (HR = 2.53, 95% CI: 1.12-5.74, P = 0.026). The combined s-iATP and APACHE II model did not show a statistically significant improvement over APACHE II alone (AUC, 0.895 vs 0.859; DeLong P = 0.081). CONCLUSION: Low s-iATP levels within 24 hours of sepsis diagnosis were independently associated with increased 28-day mortality in adult ICU patients with sepsis. s-iATP may provide functional immune information complementary to conventional severity scores, but its incremental prognostic value requires further validation in larger prospective cohorts.