Development and Validation of a Risk-Prediction Nomogram for Preoperative Blood Type and Antibody Testing in Spinal Fusion Surgery.

OBJECTIVE: With advancements in minimally invasive techniques, the use of spinal fusion surgery is rapidly increasing and transfusion rates are decreasing. Routine preoperative ABO/Rh blood type and antibody screening (T&S) laboratory tests may not be appropriate for all spinal fusion patients. Herein, we constructed a nomogram to assess patient transfusion risk based on various risk factors in patients undergoing spinal fusion surgery, so that preoperative T&S testing can be selectively scheduled in appropriate patients to reduce healthcare and patient costs. METHODS: Patients who underwent spinal fusion surgery between 01/2020 and 03/2023 were retrospectively examined and classified into the training (n = 3533, 70%) and validation (n = 1515, 30%) datasets. LASSO and multivariable logistic regression were used to analyze risk factors for blood transfusion. Nomogram predictive model was built according to the independent predictors and mode predictive power was validated using consistency index (C-index), Hosmer-Lemeshow (HL) test, calibration curve analysis and area under the curve (AUC) for receiver operating characteristic (ROC) curve. Bootstrap resampling was used for internal validation. Decision curve analysis (DCA) was applied to evaluate the model's performance in the clinic. RESULTS: Being female, age, BMI, admission route, critical patient, operative time, heart failure, end-stage renal disease or chronic kidney disease (ESRD or CKD), anemia, and coagulation defect were predictors of blood transfusion for spinal fusion. A prediction nomogram was developed according to a multivariate model with good discriminatory power (C-index = 0.887); Bootstrap resampling internal validation C-index was 0.883. Calibration curves showed strong matching between the predicted and actual probabilities of the training and validation sets. HL tests for the training and validation sets had p-values of 0.327 and 0.179, respectively, indicating good calibration. When applied to the training set, the following parameters were found: AUC: 0.895, 95% CI: 0.871-0.919, sensitivity 78.2%, specificity 86.7%, positive predictive value 29.4% and negative predictive value 98.2%. If the model were applied in the training set, 2911 T&S tests (82.4%) would be eliminated, equaling a RMB349,320 cost reduction. The AUC in the internal validation was: 0.879, 95% CI: 0.839-0.927, sensitivity 75.2%, specificity 88.8%, positive predictive value 34.3%, negative predictive value 97.9%, would eliminate 1276 T&S tests (84.2%), saving RMB 153,120. The DCA curve indicated good clinical application value. CONCLUSION: The nomogram based on 10 independent factors can help healthcare professionals predict the risk of transfusion for patients undergoing spinal fusion surgery to target preoperative T&S testing to appropriate patients and reduce healthcare costs.

Single-cell sequencing analysis reveals the relationship between tumor microenvironment cells and oxidative stress in breast cancer bone metastases.

Bone metastasis (BM) is one of the main manifestations of advanced breast cancer (BC), causing complications such as pathological fractures, which seriously affects the quality of life of patients and even leads to death. In our study, a global single-cell landscape of the tumor microenvironment was constructed using single cell RNA sequencing data from BM. BC cells were found to be reduced in the BM, while mesenchymal stem cells (MSCs), Fibroblasts and other cells were significantly more abundant in the BM. The subpopulations of these cells were further identified, and the pathways, developmental trajectories and transcriptional regulation of different subpopulations were discussed. The results suggest that with the development of BM, BC cells were vulnerable to oxidative damage, showing a high level of oxidative stress, which played a key role in cell apoptosis. Fibroblasts were obviously involved in the biological processes (BPs) related to ossification and bone remodeling, and play an important role in tumor cell inoculation to bone marrow and growth. MSC subpopulations were significantly enriched in a number of BPs associated with bone growth and development and oxidative stress and may serve as key components of BC cells homing and adhesion to the ecological niche of BM. In conclusion, our research results describe the appearance of tumor microenvironment cell subpopulations in breast cancer patients, reveal the important role of some cells in the balance of BM bone remodeling and the imbalance of BM development, and provide potential therapeutic targets for BM.

A tool for predicting overall survival in patients with Ewing sarcoma: a multicenter retrospective study.

OBJECTIVE: The aim of this study was to establish and validate a clinical prediction model for assessing the risk of metastasis and patient survival in Ewing's sarcoma (ES). METHODS: Patients diagnosed with ES from the Surveillance, Epidemiology and End Results (SEER) database for the period 2010-2016 were extracted, and the data after exclusion of vacant terms was used as the training set (n=767). Prediction models predicting patients' overall survival (OS) at 1 and 3 years were created by cox regression analysis and visualized using Nomogram and web calculator. Multicenter data from four medical institutions were used as the validation set (n=51), and the model consistency was verified using calibration plots, and receiver operating characteristic (ROC) verified the predictive ability of the model. Finally, a clinical decision curve was used to demonstrate the clinical utility of the model. RESULTS: The results of multivariate cox regression showed that age, , bone metastasis, tumor size, and chemotherapy were independent prognostic factors of ES patients. Internal and external validation results: calibration plots showed that the model had a good agreement for patient survival at 1 and 3 years; ROC showed that it possessed a good predictive ability and clinical decision curve proved that it possessed good clinical utility. CONCLUSIONS: The tool built in this paper to predict 1- and 3-year survival in ES patients ( https://drwenleli0910.shinyapps.io/EwingApp/ ) has a good identification and predictive power.

Development of a borosilicate bioactive glass scaffold incorporating calcitonin gene-related peptide for tissue engineering.

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350-400 µm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7 days of immersion in SBF, reaching a final released concentration of 893.00 ± 63.30 ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications.

FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis.

PURPOSE: Postmenopausal osteoporosis (PMOP) is a common and debilitating chronic disease, but it has just no cure options. The objective of this study was to identify genes associated with osteoporosis and reveal potential therapeutic targets. METHODS: Expression profiles from GSE13850 and GSE56815 datasets were combined for differential expression analysis. Extraction of intersecting genes from the combined datasets and the differentially expressed genes in GSE56814 were performed to construct a multi-scale embedded gene co-expression network analysis (MEGENA) to obtain module genes. Module genes with an area under the receiver operating characteristic curve (AUC) >0.60 were chosen to construct the least absolute shrinkage and selection operator (LASSO) model to obtain feature genes. A regulated network was constructed using differentially expressed micro-RNAs (miRNAs) in GSE74209 and feature genes. Finally, key genetic pathways and pathways of the Kyoto Encyclopedia of Genes and Genomes were identified and explored. RESULTS: The commonly identified differentially expressed genes involve oxidative phosphorylation and caffeine metabolism. We identified 66 modules with 2354 module genes based on MEGENA. CARD8, FOXO4, IL1R2, MPHOSPH6, MPRIP, MYOM1, PRR5L and YIPF4 were identified as feature genes by the LASSO model. Furthermore, predicted miRNA target genes included 8 genes associated with PMOP. The largest AUC was observed for FOXO4, which was found at the nexus of feature genes and miRNA-regulated genes and which correlated with the upregulation of dendritic cells. Moreover, FOXO4 was found to be involved in ABC transporters, as well as cocaine and nicotine addiction. CONCLUSION: FOXO4 may serve as potential biomarker and therapeutic target for PMOP.

The global burden of decubitus ulcers from 1990 to 2019.

There are no studies assessing the epidemiology and burden of decubitus ulcers at global, regional, and national levels. We aim to report this issue from 1990 to 2019 by extracting data from the Global Burden of Disease Study (GBD) 2019 and stratifying it by age, gender, and socio-demographic index (SDI). Globally, the number of prevalent cases of decubitus ulcers in 2019 is 0.85 (95% UI 0.78 to 0.94) million. The age-standardized rates of prevalence, incidence, and years lived with disability (YLDs) in 2019 are 11.3 (95% UI 10.2 to 12.5), 41.8 (37.8 to 46.2), and 1.7 (1.2 to 2.2) per 100,000 population, and compared with 1990, it has decreased by 10.6% (95% UI 8.7% to 12.3%), 10.2% (8.2 to 11.9%), and 10.4% (8.1 to 12.5%), respectively. In addition, the global prevalence rate of decubitus ulcers increases with age, peaking at the > 95 age group among men and women. At the regional and national levels, we observe a positive correlation between age-standardized YLDs and SDI. Malaysia, Saudi Arabia, and Thailand experienced the most significant increases in age-standardized prevalence rates at the national level. Finally, we concluded that the age-standardized prevalence, incidence, and YLDs rates of decubitus ulcer declined from 1990 to 2019, with significant regional differences. In order to monitor the dynamic changes of decubitus ulcers burden, it is recommended to improve the quality of decubitus ulcer health data in all regions and countries.

Correlations between posterior longitudinal ligament status and size of bone fragment in thoracolumbar burst fractures.

This study aim to determine the correlation between the size of bone fragment and injury of posterior longitudinal ligament (PLL). In this study retrospectively analyze medical chart of patients with thoracolumbar burst fractures from June 2010 to December 2012. Patients were divided into two groups (Intact group and Disrupted group) according to the result of MRI assessing status of PLL. All the fractures were classified according to the Arbeit Fuer Osteoosynthese (AO) classification system. Neurological status was classified according to American Spinal Injury Association (ASIA). Mimics measured the height and width of bone fragment (HBF and WBF), transverse canal diameter (TCD) and calculate the height of posterior wall of the injury vertebrae, ratio of height of bone fragment occupying height of posterior wall of vertebrae body (RHBF) and ratio of width of bone fragment occupying transverse canal diameter (RWBF). The results indicated that 52 patients were included in the study. There are 31 patients with intact PLL and 21 patients with disrupted PLL. There was significant difference on the HBF (t = -3.646, P = 0.001), WBF (t = -3.615, P = 0.001), RHBF (t = -4.124, P = 0.000) and RWBF (t = -3.305, P = 0.002) between the intact group and injury group. There was a significant correlation between injury of PLL and ASIA grade (OR = 7.851, P = 0.005), and AO classification (OR = 6.401, P = 0.011), and RHBF (OR = 6.455, P = 0.011), and HBF (OR = 5.208, P = 0.022). In conclusion, the results of this study indicate that AO classification, ASIA grade, HBF and RHBF could act as the predictors of injury of PLL.

The association of MDM2 c.346G>A genetic variant with the risk of osteosarcoma in Chinese.

Previous studies suggest that the MDM2 gene is one of the most important candidate genes for influencing the risk of osteosarcoma. This study aims to investigate the potential association of MDM2 c.346G>A genetic variant with the risk of osteosarcoma in Chinese. A total of 738 subjects were recruited in this study. The genotypes of MDM2 c.346G>A genetic variant were detected by the created restriction site-polymerase chain reaction. Our data suggest that the MDM2 c.346G>A genetic variant is associated with the increased risk of osteosarcoma in the homozygote comparison (AA vs. GG: odds ratio [OR]=2.36, 95% confidence interval [CI] 1.30-4.28, χ2=8.35, p=0.004), recessive model (AA vs. GA/GG: OR=2.32, 95% CI 1.30-4.13, χ2=8.50, p=0.004), and allele comparison (A vs. G: OR=1.27, 95% CI 1.01-1.60, χ2=4.34, p=0.037). Results from this study indicated that the allele-A and genotype-AA of MDM2 c.346G>A genetic variant could be an increased risk factor for the susceptibility to osteosarcoma and might be used as a potential molecular marker for evaluating the risk of osteosarcoma.

Two-stage nicking enzyme signal amplification combined with DNAzyme amplification for the detection of bone morphogenetic protein 6 mRNA.

Highly sensitive detection of bone morphogenetic protein 6 (BMP6) mRNA is essential to monitor bone regeneration in the regenerating defects. In this work, we proposed a quantitative approach based on two-stage nicking enzyme signal amplification (NESA) and DNAzyme amplification for highly sensitive detection of BMP6 mRNA. The two-stage NESA involves two templates and two-stage amplification reactions under isothermal conditions. The first template contains two repeat sequences that could hybridize to the target RNA, triggering an exponential amplification. The amplified product was a short single-stranded DNA with the same sequence as the target RNA. The single-stranded DNA can trigger another linear NESA and produces a large amount of horseradish peroxidase (HRP)-mimicking G-quadruplex DNAzyme. This proposed assay showed a quantitative analysis of BMP6 mRNA in a wide range from 1 fM to 100 nM with a detection limit of 0.01 fM.

Transcript levels of major interleukins in relation to the clinicopathological profile of patients with tuberculous intervertebral discs and healthy controls.

OBJECTIVES: The purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27) and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs. METHODS: Clinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction. RESULTS: IL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05). Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05). Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05). CONCLUSIONS: The experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis.

[Comminuted distal humeral fractures treated with Y-type anatomical plate].

OBJECTIVE: To explore the efficacy of Y-type anatomical plate in patients with distal humeral fracture. METHODS: Thirty three patients suffered from comminuted distal humeral fracture undertook the operation. Among them, 15 were supracondyle fracture, and the other 18 were intercondyle fracture. All patients were treated with middle post elbow incision, reposition, and fixed with Y-type anatomical steel plate. RESULTS: All patients were followed up for 16 months after the operation, and all fractures healed. The average healing time was 3. 5 months. The elbow joint function according to Aitken and Rombeck's elbow function rating system was evaluated, and the results were as follows: the function recovery was excellent in 29 patients, good in 2 and fair in the other 2 patients. The excellence rate was 93. 9%. CONCLUSION: Y-type anatomical steel plate is excellent in the treatment of distal humeral fracture.