Development and validation of models for predicting mortality in intertrochanteric fracture surgery patients with perioperative blood transfusion: a prospective multicenter cohort study.

BACKGROUND: The association between allogenic blood transfusions (ABT) and all-cause mortality in surgically treated hip fracture patients with perioperative transfusion (STHFPT) remained unknown. We aim to introduce transfusion-related factors, new variables to develop and validate models to predict mortality in these patients. METHODS: A prospective multicenter cohort study was conducted with STHFPT hospitalized during Jan. 2018 and Jun. 2021. The database was divided into training cohort and validation cohort in a ratio of 70% to 30% using the randomization method. All participants received a minimum of 2-year follow-up and all participants' overall and eight time-specific survival status were recorded. Prediction models were developed using multivariate logistic regression and Cox regression for variable selection. Model performance was measured by determining discrimination, calibration, overall model performance or precision, and utility. Sensitivity analyses were performed to test robustness of the results. RESULTS: A total of 7074 consecutive patients were prospectively screened and assessed for eligibility to participate. Finally, 2490 patients met our inclusion and exclusion criteria and 1743 (70%) patients were randomized to the training cohort and 747 (30%) to the validation cohort. The median duration of follow-up was 38.4 months (IQR 28.0-62.0). Our novel models highlight that preoperative transfusion is of significance for short-term mortality while mid-term outcomes are predominantly determined by severe complications, pulmonary complications, and advanced age. Our models showed high discriminative power, good calibration and precision for mortality prediction in both training and validation cohorts, especially in short-term mortality prediction. CONCLUSIONS: We introduce transfusion-related factors, new variables to develop and validate models to predict mortality with STHFPT. The models can be further tested and updated with the ultimate goal of assisting in optimizing individual transfusion strategy.

Efficacy of surgical intervention over conservative management in intertrochanteric fractures among nonagenarians and centenarians: a prospective cohort study.

BACKGROUND: Optimal treatment strategy for nonagenarians and centenarians with hip fractures (NCHF) remained unknown. The authors aimed to compare the outcomes of surgical and conservative management in NCHF. METHODS: A prospective cohort study was conducted based on CPMHF database with NCHF patients hospitalized during 2014-2020. Comorbidities were evaluated by mECM score and restricted cubic spline was utilized to visually assess the dose-effect relationship between the mECM and outcomes. Propensity score matching was performed to balance baseline characteristics between nonsurgical and surgical groups. Multivariate logistic regression, Cox proportional hazard analysis, and survival analysis were employed for unfavorable outcomes (UFO) evaluation. Competing risk of death were analyzed based on Fine and Gray's hazard model and then constructed nomogram models for predicting survival rates. Subgroup analyses were used to determine potential population heterogeneity and sensitivity analyses were performed to test robustness of the results. RESULTS: The authors found increasing trends for UFO with the increase in the mECM score, and that high mECM score (HMS, ≥3) was independently associated with a 2.42-fold (95% CI: 2.07-3.54; P =0.024) increased risk of UFO, which remained significant after considering the competing role of death and were more pronounced in nonsurgical treatment, women, no insurance, and patients with spouse (all P for interaction <0.05). Surgical intervention was identified to be significant protective factors for UFO (RR, 0.59; 95% CI: 0.46-0.75; P <0.001) and severe complications (RR, 0.63; 95% CI: 0.41-0.96; P =0.033) after propensity score matching, as well as survival (HR, 0.40, 95% CI: 0.28-0.58; P <0.001), which remained significant after considering the competing role of death and in all sensitivity analyses and were more pronounced in HMS participants ( P for interaction=0.006). Subgroup analyses revealed surgical patients with HMS had a significantly higher UFO rate (excluding death, P <0.001) while nonsurgical patients with HMS had higher mortality rate as compared to the others ( P =0.005). CONCLUSION: Surgical treatment for NCHF yields better outcomes compared to conservative treatment.

Formononetin attenuates osteoclast differentiation and calcium loss by mediating transcription factor AP-1 in type I diabetic mice.

Formononetin (FMN) has been reported as a prospective antiosteoporotic medication. However, the antiosteoporotic properties of FMN are still unclear in a mouse model with diabetes-induced osteoporosis. An osteoporotic or osteopenic mouse model with type I diabetes mellitus (T1DM) was established using streptozotocin (40 mg/kg) injection for 5 consecutive days. After 12 weeks with FMN intragastric administration (0.5, 5, 20 mg/kg), the antiosteoporotic activity of FMN was evaluated in T1DM mice. FMN supplementation effectively improves Ca excretion and trabecular bone degeneration and impedes osteoclast differentiation and function to attenuate hyperglycemia-induced bone deterioration. In addition, FMN inhibited activating protein 1 (AP-1) and osteoclast-specific gene expression, Nfatc1, Ctsk, and TRAP. The administration of FMN has a beneficial effect to attenuate hyperglycemia-induced bone deteriorations, including osteoclastogenesis, trabecular bone, and Ca loss. Our study provided a prospective medication for the treatment of T1DM-related osteopenia or osteoporosis with FMN.

An experimental study on stress-shielding effects of locked compression plates in fixing intact dog femur.

BACKGROUND: In orthopedic application, stress-shielding effects of implant materials cause bone loss, which often induces porosis, delayed bone healing, and other complications. We aimed to compare the stress-shielding effects of locked compression plate (LCP) and limited-contact dynamic compression plate (LC-DCP) in dogs with plate-fixed femurs. METHODS: Bilateral intact femurs of 24 adult dogs were fixed by adult forearm 9-hole titanium plates using minimally invasive plate osteosynthesis (MIPPO) technology, with LCP on the left and LC-DCP on the right femurs. Dogs were sacrificed at 6 weeks, 12 weeks, and 24 weeks after surgery, and bone specimens were used to evaluate the efficacies of different fixing methods on bones through X-ray, dual-energy X-ray absorptiometry (DEXA), histology, MicroCT, and biomechanics analyses. RESULTS: X-ray results showed significant callus formation and periosteal reaction in the LC-DCP group. Bone cell morphology, degree of osteoporosis, and bone mineral density (BMD) changes of the LCP group were significantly better than that of the LC-DCP group. MicroCT results showed that the LCP group had significantly reduced degree of cortical bone osteoporosis than the LC-DCP group. Tissue mineral density (TMD) in the LCP group was higher than that in the LC-DCP group at different time points (6 weeks, 12 weeks, and 24 weeks). Biomechanics analyses demonstrated that the compressive strength and flexural strength of bones fixed by LCP were better than that by LC-DCP. CONCLUSIONS: Stress-shielding effects of LCP are significantly weaker than that of LC-DCP, which is beneficial to new bone formation and fracture healing, and LCP can be widely used in clinic for fracture fixation.

Assessment of osteoinduction using a porous hydroxyapatite coating prepared by micro-arc oxidation on a new titanium alloy.

Surface modification and material improvement is now an important way to improve the osseointegration between bone and uncemented prothesis. The purpose of this study was to investigate the bone ingrowth potential of porous hydroxyapatite (HA) coatings prepared by micro-arc oxidation (MAO) on Ti-3Zr-2Sn-3Mo-25Nb, a new titanium alloy. HA-coated specimens were implanted in the left proximal femoral medullary canal of beagles for 4, 12, and 24 weeks, and uncoated specimens were implanted in the right as a control. The surface morphology and phase composition were investigated with environmental scanning electron microscopy and X-ray diffractometry. The bone ingrowth was assessed by histomorphometry. A pull-out test was performed to assess the mechanical performance of the bone-implant interface. A porous coating was well prepared on the new titanium alloy by using the MAO method. The bone-to-implant contact was significantly higher for the HA-coated group compared to that in the uncoated group. Mechanical tests showed that the HA-coated group had significantly higher maximum force at the bone-implant interface compared to the uncoated specimens. MAO is a suitable coating approach for this new titanium alloy. The HA coating prepared by this approach can significantly promote bone ingrowth and the mechanical performance of the bone-implant interface.

Role of miR-146a in human chondrocyte apoptosis in response to mechanical pressure injury in vitro.

MicroRNA (miR)-146a is known to be overexpressed in osteoarthritis (OA). However, the role of miR-146a in OA has not yet been fully elucidated. In the present study, we applied mechanical pressure of 10 MPa to human chondrocytes for 60 min in order to investigate the expression of miR-146a and apoptosis following the mechanical pressure injury. Normal human chondrocytes were transfected with an miR-146a mimic or an inhibitor to regulate miR-146a expression. Potential target genes of miR-146a were predicted using bioinformatics. Moreover, luciferase reporter assay confirmed that Smad4 was a direct target of miR-146a. The expression levels of miR-146a, Smad4 and vascular endothelial growth factor (VEGF) were quantified by quantitative reverse transcription PCR and/or western blot analysis. The effects of miR-146a on apoptosis were detected by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry. The results indicated that mechanical pressure affected chondrocyte viability and induced the early apoptosis of chondrocytes. Mechanical pressure injury increased the expression levels of miR-146a and VEGF and decreased the levels of Smad4 in the chondrocytes. In the human chondrocytes, the upregulation of miR-146a induced apoptosis, upregulated VEGF expression and downregulated Smad4 expression. In addition, the knockdown of miR-146a reduced cell apoptosis, upregulated Smad4 expression and downregulated VEGF expression. Smad4 was identified as a direct target of miR-146a by harboring a miR­146a binding sequence in the 3'-untranslated region (3'-UTR) of its mRNA. Furthermore, the upregulation of VEGF induced by miR­146a was mediated by Smad4 in the chondrocytes subjected to mechanical pressure injury. These results demonstrated that miR-146a was overexpressed in our chondrocyte model of experimentally induced human mechanical injury, accompanied by the upregulation of VEGF and the downregulation of Smad4 in vitro. Moreover, our data suggest that miR-146a is involved in human chondrocyte apoptosis in response to mechanical injury, and may contribute to the mechanical injury of chondrocytes, as well as to the pathogenesis of OA by increasing the levels of VEGF and damaging the transforming growth factor (TGF)-ß signaling pathway through the targeted inhibition of Smad4 in cartilage.