Integrated nutritional-inflammatory and frailty-based model for mortality risk stratification following hip fracture...

Mortality after hip-fracture surgery remains high, and current prognostic tools often assess frailty or nutritional-inflammatory status separately. We hypothesised that integrating frailty with composite immune-nutritional indices, particularly the C-reactive protein-albumin-lymphocyte (CALLY) index and the Global Immuno-Nutrition Inflammation (GINI) index, would enhance mortality risk stratification in older hip-fracture patients.

This multicentre retrospective cohort study included 517 patients aged ≥ 65 years who underwent surgical treatment for hip fracture between 2018 and 2024. Baseline data included demographics, established frailty measures, fracture characteristics, and surgical delay. Nutritional-inflammatory status was assessed using routine laboratory-based indices, including albumin, C-reactive protein, Prognostic Nutritional Index, Geriatric Nutritional Risk Index, CALLY, and GINI. Multivariable logistic regression models were developed to predict in-hospital, 30-day, 90-day, and 1-year mortality. Model discrimination, calibration, and reclassification performance were evaluated using AUC, information criteria, calibration metrics (Hosmer-Lemeshow test, Brier score), and continuous net reclassification improvement. Multicollinearity was rigorously assessed using variance inflation factors (VIF). Sensitivity and specificity were evaluated across multiple probability thresholds (0.20-0.50) to optimize clinical utility.

One-year mortality was 28.8%. Frailty measures remained independent predictors of mortality, while the addition of nutritional-inflammatory indices significantly improved 1-year risk stratification (AUC increase from 0.666 to 0.673; NRI + 14.9%). Incorporation of CALLY and GINI provided further, albeit modest, improvement (AUC 0.678; NRI + 11.7%). All models demonstrated excellent calibration (Hosmer-Lemeshow p > 0.69, Brier scores 0.12-0.19). Patients in the lowest CALLY or highest GINI quartiles exhibited substantially higher 1-year mortality (~ 40%) compared with those in the highest CALLY or lowest GINI quartiles (~ 18%; p < 0.001). However, severe multicollinearity among frailty scores (VIF 12-34) and nutritional indices (VIF 139-277) resulted in paradoxical coefficient estimates. At the optimal probability threshold (0.34), Model 3 achieved sensitivity of 51.7% and specificity of 75.0% for 1-year mortality prediction.

An integrated nutritional-inflammatory and frailty-based approach, incorporating the CALLY and GINI indices derived from routine laboratory parameters, offers clinically meaningful improvement in mortality risk stratification after hip-fracture surgery. While multicollinearity limits coefficient interpretability, excellent calibration and improved risk reclassification support clinical utility. Threshold optimization (0.30-0.35) is recommended to maximize sensitivity for screening purposes. Prospective validation and nutrition-targeted interventional studies are warranted.