Development and Validation of a Nomogram for Adverse Outcomes of Geriatric Trauma Patients Based on Frailty Syndrome.

Purpose: Currently, assessing trauma severity alone in geriatric trauma patients (GTPs) cannot accurately predict the risk of serious adverse outcomes during hospitalization. As an emerging concept in recent years, frailty syndrome is closely related to the poor prognosis of many diseases in elderly patients, including trauma. A logistic model for predicting adverse outcomes in elderly trauma patients during hospitalization was constructed in elderly patients, and the predictive efficacy of the model was verified. Patients and Methods: Trauma patients aged ≥65 years between June 2020 and September 2021 were selected and randomly divided into a training set and validation set at a ratio of 3:1. Mid arm muscle circumference (MAMC) was measured to determine the degree of frailty. LASSO regression was used to screen appropriate variables for the construction of a prognostic model. The logistic regression model was established and presented in the form of a nomogram. Calibration curves and ROC curves were used to verify the performance of the model. Results: A total of 209 patients were enrolled, including 143 (68.4%) males and 66 (31.6%) females, with an average age of 70.8 ± 4.8 years. Ageless Charlson comorbidity index, BT unit, ISS, GCS, MAMC, prealbumin and lactic acid levels were screened by LASSO regression to construct a prognostic model. The AUC of the ROC analysis prediction model was 0.89 (95% CI 0.80-0.97) in the validation set. The results of the Hosmer-Lemeshow test for the validation set were χ2 = 11.23, P = 0.189. Conclusion: The prognostic model of adverse outcomes in GTPs has good accuracy and differentiation, which can improve the prediction results of risk stratification of GTPs during hospitalization by medical staff and provide a new idea for prognostic prediction.

Predictive Value of the Geriatric Trauma Outcome Score in Older Patients After Trauma: A Retrospective Cohort Study.

Purpose: The Geriatric Trauma Outcome Score (GTOS) has been developed and indicate to be a valid prognostic tool for the prediction of mortality in geriatric trauma patients (GTPs) during hospitalization. However, the predictive value of the GTOS for morbidity is still unclear. We aimed to evaluate the association between GTOS, morbidity and mortality in GTPs. Patients and Methods: We performed a retrospective cohort study between June 1, 2016, and May 31, 2020, and collected data for patients aged 65 years or older. These patients were treated at the Trauma Center of Tongji Hospital, Wuhan, China. Clinical data were retrieved from the trauma registry. The GTOS was calculated with the following formula: age + ISS * 2.5 + 22 (if any packed red blood cells were transfused within 24 hours after admission). The outcomes were mortality, morbidity, length of hospital stay (LOS), and functional outcome at discharge. Results: A total of 485 patients were enrolled: 214 (44.1%) were classified into the low-GTOS group, and 271 (55.9%) were classified into the high-GTOS group. The median (IQR) age was 68 (66-71) years; 361 (74.4%) were male. The most common mechanism of injury was vehicle collision (66.4%), followed by falls <2 m (19.6%). The median (IQR) ISS was 18 (14-22). The median (IQR) GCS was 13 (9-15). A high GTOS was associated with high rates of all-cause mortality (13.3% vs 0.9%, P < 0.001), complications (88.2% vs 31.8%, P < 0.001), unplanned intubation (19.2% vs 1.4%, P < 0.001), and unplanned admissions to the intensive care unit (8.5% vs 0.5%, P < 0.001). In multivariable logistic regression analysis, GTOS was associated with morbidity (OR 1.07, 95% CI, 1.05-1.09, p < 0.001) and mortality (OR 1.04, 95% CI, 1.02-1.06, p < 0.001). Conclusion: The GTOS is an independent predictor of morbidity and mortality in GTPs, and it will help us identify patients at high risk on admission.

Inhibition of the C3a receptor attenuates sepsis-induced acute lung injury by suppressing pyroptosis of the pulmonary vascular endothelial cells.

Acute lung injury (ALI) is the leading cause of bacterial sepsis-related death because of disrupted pulmonary endothelial barrier, resulting in protein-rich pulmonary oedema, an influx of pro-inflammatory cells and refractory hypoxaemia. Several studies have reported that C3a levels are significantly higher in organs with sepsis and their peripheral organs and are closely associated with organ dysfunction and poor prognosis in sepsis. However, the role of the C3a complement in sepsis ALI remains unclear. Therefore, this study aimed to investigate the important role and mechanism of C3a in preventing the occurrence of pyroptosis (a pro-inflammatory form of cell death) to protect the lung endothelial cells (ECs) in sepsis-induced ALI. A septic mouse model was established with cecal ligation and puncture (CLP), which demonstrated that C3a mediated EC pyroptosis through its C3aR receptor. Furthermore, inhibition of the C3a-C3aR axis could block both NLRP3/caspase-1 and caspase-11 pathways, thus preventing pulmonary EC from pyroptosis. These results indicate that inhibition of the C3A-C3AR complement axis can inhibit pulmonary vascular EC pyroptosis, a potential target for the treatment of ALI.

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD.

Intestinal barrier dysfunction is associated with the occurrence and development of sepsis. Further, aerobic glycolysis plays an essential role in inflammation and cell death. This study is aimed at investigating the protective effect and mechanism of PFKFB3 inhibition on intestinal barrier dysfunction in sepsis mice. Sepsis mouse models were established by cecal ligation and puncture (CLP) in wild-type mice and Gsdmd-/- mice. The results showed that the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in the small intestines was significantly upregulated in sepsis. 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), the specific inhibitor of PFKFB3, and Gsdmd gene knockout significantly inhibited the inflammatory response and cell death caused by sepsis, thus alleviating intestinal damage and barrier dysfunction. 3PO was also shown to significantly inhibit oxidative stress and NLRP3/caspase-1/GSDMD-dependent cell pyroptosis in the small intestines. The in vitro studies revealed that 3PO reduced NLRP3/caspase-1/GSDMD-dependent cell pyroptosis by inhibiting ROS. Taken together, our results suggest that PFKFB3 is involved in inflammation, oxidative stress, and pyroptosis during sepsis and enhances intestinal damage, which may provide important clues about the potential targets to be exploited in this highly lethal disease.