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Admission D-Dimer for Early Risk Stratification of in-Hospital Mortality in Adults with Non-HIV Cryptococcal
Qiong Wu1, Xiangzhi Xiao2, Huashan Zhou3
1Department of Neurosurgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People's Republic of China.
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.
Insights
Elevated D-dimer levels in adults with cryptococcal meningitis (CM) without HIV infection are linked to higher in-hospital mortality. This finding suggests D-dimer could aid early risk assessment for non-HIV CM patients.
Area of Science:
- Neurology
- Infectious Diseases
- Hematology
Background:
- Cryptococcal meningitis (CM) is a severe fungal infection of the central nervous system.
- Prognostic indicators for non-HIV-associated CM are limited.
- D-dimer, a marker of coagulation activation, has unclear prognostic value in non-HIV CM.
Purpose of the Study:
- To investigate the association between admission D-dimer levels and in-hospital mortality in adults with non-HIV CM.
- To identify early prognostic indicators for non-HIV CM.
Main Methods:
- Retrospective study of 104 adults with confirmed non-HIV CM.
- Analysis of in-hospital mortality as the primary outcome.
- Multivariable logistic regression with Firth's penalized method and multiple imputation for missing data.
- Model performance assessed using ROC analysis and internal validation.
Main Results:
- 21.2% of patients died during hospitalization.
- Admission D-dimer was independently associated with in-hospital mortality (OR 1.41, P=0.033).
- The predictive model demonstrated acceptable discrimination (AUC 0.753 after validation).
Conclusions:
- Elevated admission D-dimer is an independent predictor of mortality in non-HIV CM.
- D-dimer may assist in early risk stratification for these patients.
- Further external validation is needed before clinical use of the predictive model.
