ABSTRACT
Objective: With a rapidly aging global population, the assessment of mortality risk following hip fracture in older adults has received increasing attention. Recently, the system inflammation response index (SIRI) has been identified as a novel prognostic marker to reflect both systemic inflammation and immune status. However, it is not yet known whether SIRI is a potential predictor of subsequent death in hip fracture patients. Therefore, this study aimed to investigate the association between SIRI and mortality in older patients with hip fracture. Methods: A total of 1,206 older hip fracture patients undergoing surgery between January 2013 and December 2022 were consecutively derived from our longitudinal database. Patients were divided into three groups according to SIRI tertiles, calculated as neutrophil × monocyte / lymphocyte. Survival status was obtained from medical records or telephone interviews, and the study outcome was all-cause mortality after hip fracture at the longest follow-up. Multivariate Cox proportional hazard model and restricted cubic spline (RCS) regression model were used to evaluate the association between SIRI and mortality. Moreover, a series of sensitivity analyses were conducted to further validate the robustness of the association. Results: During a median follow-up of 43.85 months, 337 patients (27.94%) died. After full adjustment, each unit increase in SIRI was significantly associated with a 2.2% increase in overall mortality (95% confidence interval [CI]: 1.001-1.042, p = 0.029). Similarly, compared with the first tertile of SIRI, the second and third tertile showed a 1.335-fold (95% CI: 1.011-1.762, p = 0.042) and 1.447-fold (95% CI, 1.093-1.917, p = 0.010) higher risk of death. Sensitivity analyses confirmed the stability of the association. Moreover, RCS analysis revealed a positive non-linear relationship between SIRI and mortality (P for nonlinearity = 0.021). Conclusion: High SIRI level at admission was significantly and positively associated with an increased risk of death, suggesting that SIRI may be an independent predictor of mortality in older patients with hip fracture.
ABSTRACT
This study aims to characterize the bone-protecting effects of Alpha-lipoic acid (ALA), a potent antioxidant, against the detrimental effects of the coexistence of type 2 diabetes mellitus (T2DM) and postmenopausal osteoporosis (POP) and identify the possible mechanisms with particular reference to its modulation of YAP/Glut4 pathway. The T2DM and POP coexisting model was induced in mice by high fat diet (HFD) + Streptozocin (STZ) + ovariectomy (OVX). The mice in the treatment groups were given ALA for 10 weeks. In the in vitro study, MC3T3-E1 cells were induced with 500 µM methylglyoxal for 24 h with or without pretreatment with ALA for 24 h. The oxidative and antioxidative biomarkers, bone microarchitecture, histo-morphology, and related protein expression of apoptosis, osteogenic differentiation and the YAP/Glut4 pathway were detected. The results showed ALA could improve glucose tolerance, inhibit oxidative stress and apoptosis and alleviate bone loss. Further study by siRNA technology revealed that the YAP/Glut4 pathway was implicated in the pathogenesis of bone loss due to the coexistence of T2DM and POP. Taken together, the present study has demonstrated for the first time that ALA exerts potent protective effects against bone loss in T2DM and POP coexisting conditions by modulating the YAP/Glut4 pathway.