Admission D-Dimer for Early Risk Stratification of in-Hospital Mortality in Adults with Non-HIV Cryptococcal Meningitis: A Retrospective Cohort Study.

BACKGROUND

Cryptococcal meningitis (CM) is a life-threatening central nervous system fungal infection. In adults without human immunodeficiency virus (HIV) infection, early prognostic indicators remain limited. D-dimer reflects activation of coagulation and fibrinolysis and may provide prognostic information in severe infections, but its significance in non-HIV CM is unclear.

METHODS

We retrospectively included consecutive adults with microbiologically confirmed non-HIV CM admitted to a tertiary teaching hospital from January 2012 to December 2023. The primary outcome was all-cause in-hospital mortality. Missing data were handled using multiple imputation. Candidate predictors were selected using least absolute shrinkage and selection operator regression across five imputed datasets. Multivariable analysis used Firth's penalized logistic regression, and coefficients were pooled according to Rubin's rules. Model performance was assessed using receiver operating characteristic analysis, calibration plots, decision curve analysis, and bootstrap internal validation.

RESULTS

Among 104 patients, 22 (21.2%) died during hospitalization. Admission D-dimer was independently associated with in-hospital mortality (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.03-1.94, P = 0.033). Cerebral infarction, cerebrospinal fluid (CSF) adenosine deaminase (ADA), and CSF cryptococcal antigen positivity were retained in the exploratory model but were not statistically significant. The model showed acceptable apparent discrimination (area under the receiver operating characteristic curve [AUC] 0.793, 95% CI 0.675-0.911). Bootstrap internal validation yielded an optimism-corrected AUC of 0.753 and calibration slope of 0.790. Log-transformed D-dimer showed directionally consistent results.

CONCLUSION

Elevated admission D-dimer was independently associated with in-hospital mortality in adults with non-HIV CM. D-dimer may help early risk stratification, but the exploratory model requires external validation before clinical implementation.