Construction and validation of a risk prediction model for delayed discharge in elderly patients with hip fracture.

BACKGROUND: Because of their poor physical state, elderly hip fracture patients commonly require prolonged hospitalization, resulting in a drop in bed circulation rate and an increased financial burden. There are currently few predictive models for delayed hospital discharge for hip fractures. This research aimed to develop the optimal model for delayed hospital discharge for hip fractures in order to support clinical decision-making. METHODS: This case-control research consisted of 1259 patients who were continuously hospitalized in the orthopedic unit of an acute hospital in Tianjin due to a fragility hip fracture between January and December 2021. Delayed discharge was defined as a hospital stay of more than 11 days. The prediction model was constructed through the use of a Cox proportional hazards regression model. Furthermore, the constructed prediction model was transformed into a nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). the STROBE checklist was used as the reporting guideline. RESULTS: The risk prediction model developed contained the Charlson Comorbidity Index (CCI), preoperative waiting time, anemia, hypoalbuminemia, and lower limbs arteriosclerosis. The AUC for the risk of delayed discharge was in the training set was 0.820 (95% CI,0.79 ~ 0.85) and 0.817 in the testing sets. The calibration revealed that the forecasted cumulative risk and observed probability of delayed discharge were quite similar. Using the risk prediction model, a higher net benefit was observed than when considered all patients were at high risk, demonstrating good clinical usefulness. CONCLUSION: Our prediction models could support policymakers in developing strategies for the optimal management of hip fracture patients, with a particular emphasis on individuals at high risk of prolonged LOS.

Identification and characterization of the conserved nucleoside-binding sites in the Epstein-Barr virus thymidine kinase.

Thymidine kinase (TK), encoded by EBV (Epstein-Barr virus), is an attractive target for antiviral therapy and provides a novel approach to the treatment of EBV-associated malignancies. Despite the extensive use of nucleoside analogues for the treatment of viral infections and cancer, the structure-function relationship of EBV TK has been addressed rarely. In the absence of any structural information, we sought to identify and elucidate the functional roles of amino acids in the nucleoside-binding site using site-directed mutagenesis. Through alignment with other human herpesviral TK protein sequences, we predicted that certain conserved regions comprise the nucleoside-binding site of EBV TK and, through site-directed mutagenesis, showed significant changes in activity and binding affinity for thymidine of site 3 (-DRH-) and 4 (-VFP-) mutants. For site 3, only mutants D392E (Asp392-->Glu) and R393H retain activity, indicating that a negative charge is important for Asp392 and a positive charge is required for Arg393. The increased binding affinities of these two mutants for 3'-deoxy-2',3'-didehydrothymidine suggest that the two residues are also important for substrate selection. Interestingly, the changed metal-ion usage pattern of D392E reveals that Asp392 plays multiple roles in this region. His394 cannot be compensated by other amino acids, also indicating a crucial role. In site 4, the F402Y mutant retains full activity; however, F402S retains only 60% relative activity. Strikingly, when Phe402 is substituted with serine residue, the original preferred pyrimidine substrates, such as 3'-azido-3'-deoxythymidine, iododeoxyuridine and beta-L-5-iododioxolane uracil (L-form substrate), have decreased competitiveness with thymidine, suggesting that Phe402 plays a crucial role in substrate specificity and that the aromatic ring is important for function.