Potential biomarkers that discriminate rheumatoid arthritis and osteoarthritis based on the analysis and validation of datasets.

BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) share some similar arthritic symptoms, but different mechanisms underlie the pathogenesis of these two diseases. Analysis of differentially expressed molecules in rheumatoid arthritis and osteoarthritis may assist in improving diagnosis and treatment strategies in clinical practice. METHODS: Microarray and RNA-seq data were acquired from the gene expression omnibus database. Differentially expressed genes (DEGs) were identified using Bioconductor packages. Receiver operating characteristic curves were plotted to assess performance. Gene ontology enrichment analysis was conducted using the clusterProfiler application. During validation, synovial fluid was harvested from patients who had undergone in-hospital joint replacement, in which the expression of proteins was measured using enzyme-linked immunosorbent assays. RESULTS: Compared with OA samples, RA samples showed 14 genes to be upregulated and 3 to be downregulated. Gene ontology analysis indicated that DEGs principally included molecules responsible for the regulation of a synovial tissue inflammatory response. Seven genes displayed a good discriminatory power with an AUC higher than 0.90. ADAMDEC1 was the biomarker that most clearly discriminated RA from OA in the database, exhibiting an AUC of 0.999, a sensitivity of 100%, and a specificity of 97.8%. Following validation, the expression levels of ADAMDEC1 in the synovial fluid from RA patients were significantly higher than those in the synovial fluid from OA patients (P < 0.05). At the cut-off value of 1957 pg/mL, ADAMDEC1 expression in the synovial fluid discriminated RA from OA with an AUC of 0.951, a specificity of 88.6%, and a sensitivity of 92.9%. CONCLUSION: The differential expression of genes in RA compared with OA indicates potential targets for molecular diagnosis and treatment. The presence of ADAMDEC1 in synovial fluid is a good biomarker of RA.

Risk Factors and Outcomes for Preoperative Asymptomatic Pulmonary Embolism in Patients Aged 60 Years and Over with Hip Fracture.

OBJECTIVE: To investigate the risk factors for, and outcomes of, preoperative asymptomatic pulmonary embolism (PE) in patients ≥60 years old following delayed operation for hip fracture. METHODS: From March 2017 to December 2018, 90 patients aged ≥60 years with hip fracture who suffered a delay in surgery were recruited to this prospective study following admission to our hospital. Computed tomography pulmonary angiography (CTPA) was used to detect preoperative asymptomatic PE and calculated its incidence. Time from injury to admission, baseline characteristics, medical comorbidities, and blood biomarker levels were evaluated as potential risk factors. Logistic regression analysis was used to identify risk factors. Mortality and major bleeding events were recorded and compared between individuals with PE and without. Data were analyzed by t-test, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis. RESULTS: The incidence of preoperative asymptomatic PE was 18.9% (17/90 patients). In the univariate analysis, the risk factors for preoperative asymptomatic PE were male sex, hypertension, cerebrovascular accident, smoking, plasma D-dimer level, potassium level, urea level, creatinine level, and cysteine level. Multivariate logistic regression analysis showed that the risk of preoperative asymptomatic PE was higher in patients with hypertension (odds ratio [OR] = 10.048; 95% confidence interval [CI], 1.118-90.333), cerebrovascular accident (OR = 20.135; 95% CI, 1.875-216.164), smoking (OR = 48.741; 95% CI, 4.155-571.788), high plasma D-dimer levels (OR = 1.200; 95% CI, 1.062-157.300), and high plasma potassium levels (OR = 12.928; 95% CI, 1.062-157.300). All patients were followed up for 21.0 months (range, 2 to 36 months). Mortality within the first year postoperatively was higher in patients with PE (29.41% vs 9.59%, P = 0.046). CONCLUSIONS: In view of the high incidence of preoperative asymptomatic PE and the inferior prognosis in individuals with PE, routine CTPA examination for preoperative asymptomatic PE could be useful for patients aged ≥60 years with hip fracture for whom surgery is delayed.

Risk factors of perioperative blood transfusion in elderly patients with femoral intertrochanteric fracture.

This study aimed to discuss the risk factors of perioperative blood transfusion after the application of proximal femoral nail antirotation (PFNA) in the treatment of elderly patients with femoral intertrochanteric fracture (FIF). Moreover, this study also aimed to analyze the causes of perioperative blood transfusion and provide guidance for clinical treatment.Records of elderly patients with FIF who were treated with PFNA in our hospital from September 2014 to May 2017 were reviewed. They were divided into transfused and nontransfused groups. The Student t test, Chi-squared test, and Fisher exact test were used in univariate analysis of 11 variables. Multivariate logistic regression analysis was performed to analyze the possible risk factors associated with postoperative blood transfusion after the application of PFNA in elderly patients with FIF. Correlations were sought using the Spearman rank correlation analysis.The univariate analysis showed that age, sex, type of fracture, admission hemoglobin (Hb), admission albumin, and intraoperative blood loss were significantly associated with perioperative blood transfusion (P = .000, .019, .000, .000, .000, and .007, respectively). The multivariate logistic regression analysis demonstrated that age (P = .019, odds ratio [OR] = 1.062), type of fracture (P = .001, OR = 4.486), and admission Hb (P = .000, OR = 0.883) were independent risk factors of postoperative blood transfusion. We found a significant positive correlation between perioperative blood transfusion and age (r = 0.264, P = .000) and type of fracture (r = 0.409, P = .000), but a negative correlation between perioperative blood transfusion and admission Hb (r = -0.641, P = .000).The main factors affecting perioperative blood transfusion are age, fracture type, and admission Hb. These results indicate that, in high-risk patients who are older in age, more unstable fractures, and lower admission Hb, monitoring Hb concentrations during the perioperative period is important to correct severe anemia in a timely manner and avoid exacerbating existing underlying diseases and inducing severe complications.

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.

Correlation between genetic polymorphism of angiopoietin-2 gene and clinical aspects of rheumatoid arthritis.

The Angiopoietin-2 (Ang2) gene encodes angiogenic factor, and the polymorphisms of Ang2 gene predict risk of various human diseases. We want to investigate whether the single nucleotide polymorphisms (SNPs) of the Ang2 gene can predict the risk of rheumatoid arthritis (RA). Between 2016 and 2018, we recruited 335 RA patients and 700 control participants. Comparative genotyping for SNPs rs2442598, rs734701, rs1823375 and rs12674822 was performed. We found that when compared with the subjects with the A/A genotype of SNP rs2442598, the subjects with the T/T genotype were 1.78 times likely to develop RA. The subjects with C/C genotype of SNP rs734701 were 0.53 times likely to develop RA than the subjects with TT genotype, suggesting the protective effect. The subjects with G/G genotype of SNP rs1823375 were 1.77 times likely to develop RA than the subjects with C/C genotype. The subjects with A/C and C/C genotype of SNP rs11137037 were 1.65 and 2.04 times likely to develop RA than the subjects with A/A genotype. The subjects with G/T and T/T genotype of SNP rs12674822 were 2.42 and 2.25 times likely to develop RA than the subjects with G/G genotype. The T allele over rs734701 can lead to higher serum erythrocyte sedimentation rate level (p = 0.006). The A allele over rs11137037 was associated with longer duration between disease onset and blood sampling (p = 0.003). Our study suggested that Ang2 might be a diagnostic marker and therapeutic target for RA therapy. Therapeutic agents that directly or indirectly modulate the activity of Ang2 may be the promising modalities for RA treatment.

Myostatin induces tumor necrosis factor-α expression in rheumatoid arthritis synovial fibroblasts through the PI3K-Akt signaling pathway.

In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor-α (TNF-α), a well-known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose-dependently induced TNF-α expression through the phosphatidylinositol 3-kinase (PI3K)-Akt-AP-1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP-1-induced luciferase activity and activation of the c-Jun binding site on the TNF-α promoter. Our results indicated that myostatin increases TNF-α expression via the PI3K-Akt-AP-1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.

A comparative study of less invasive stabilization system and titanium elastic nailing for subtrochanteric femur fractures in older children.

The objective of this study was to compare prospectively the complications and the radiographic and clinical outcomes of reverse less invasive stabilization system (LISS) and titanium elastic nailing (TEN) for the treatment of subtrochanteric femur fractures in older children. From April 2004 to February 2012, 52 children aged from 10 to 15 years old with subtrochanteric fractures were included in this study. 26 patients were treated with reverse LISS (LISS group) and 26 children treated with titanium elastic nails (TEN group) respectively. Perioperative care was standardized. Surgical time, blood loss, length of hospitalization, hospital costs, fracture union time, full weight-bearing time and complications were analyzed. The radiologic results as well as hip functional outcomes were evaluated. The average follow-up time of LISS group was 36.5±9.3 months and TEN group was 40.2±10.6 months. No significant difference between these two groups was found in union time, full weight-bearing time and average length of hospitalization. However, the patients of LISS group had longer operation time (60.0±10.6 min vs. 40.5±7.4 min, p<0.01), more blood loss (130.0±45.0 ml vs. 15.5±10.2 ml, p<0.01), and more hospital costs (25000±700 RMB vs. 10800±500 RMB, p<0.01). The overall complication rate was significantly higher in the LISS group than in the TEN group (12/26 vs. 5/26, p=0.039). There was no significant difference between the two groups in terms of early and late radiological results. Using the Sanders score system, there were 13 excellent, 6 good and 7 fair results in the LISS group compared with 22 excellent and 4 good results in the TEN group. The excellent and good rate was significantly different between the two groups (p=0.010). Our results indicated that TEN fixation of subtrochanteric femur fractures in older children was associated with better function scores and a lower overall complication rate when compared with reverse LISS.

Risk factors for limb overgrowth after the application of titanium elastic nailing in the treatment of pediatric femoral fracture.

PURPOSE: The objective of this study was to discuss the risk factors of postoperative limb overgrowth after the application of titanium elastic nailing (TEN) in the treatment of pediatric femoral fractures as well as analyze the causes and provide guidance for clinical treatment. METHODS: The study included children with femoral fractures who were treated with TEN at our hospital from February 2005 to December 2009. Their age, gender, weight, cause of injury, having head trauma or not, fracture site, fracture type and nail-canal diameter (NCD) ratio were recorded. Student's t-test, chi-square test or Fisher's exact test was used for univariate analysis of the above factors, and then multivariate logistic regression analysis was used to analyze the possible risk factors in order to determine which ones are associated with limb overgrowth after the application of TEN to treat children with femoral fractures. RESULTS: Univariate analysis showed that the age, gender, weight, cause of injury, having head trauma or not, and the fracture site did not have a statistically significant association with limb overgrowth (P = 0.741, 0.900, 0.253, 0.739, 0.967 and 0.105, respectively). The fracture type and NCD ratio were significantly associated with limb overgrowth (P = 0.003 and 0.000, respectively). Multivariate logistic regression analysis demonstrated that the fracture type (P = 0.021, OR = 2.757) and NCD ratio (P = 0.002, OR = 2.422) were independent risk factors for limb overgrowth. CONCLUSIONS: The main factors affecting postoperative limb overgrowth are the fracture type and NCD ratio. In order to avoid limb overgrowth, unstable fractures should be fixed as firmly as possible, and the NCD ratio should be ≥0.8.

A randomised prospective study of two different combined internal and external fixation techniques for distal tibia shaft fractures.

BACKGROUND: External fixation combined with limited open reduction and internal fixation (EF + LORIF) is a well-accepted and effective method for distal tibia shaft fractures, but it was also related to complications. The objective of this study was to compare external fixation combined with closed reduction and internal fixation (EF + CRIF) with EF + LORIF in the treatment of distal tibia shaft fractures, and explore the benefits and defects of these two techniques. METHODS: Fifty-six patients were randomised to operative stabilisation either by an external fixator combined with two closed titanium elastic nails or by external fixation combined with limited open reduction and internal fixation. Pre-operative variables included the patients' age, sex, the affected side, cause of injury, Tscherne classification of soft tissue injury, fracture pattern, and time from injury to surgery. Peri-operative variables were the operating time and the radiation time. Postoperative variables were wound problems and other complications, union time, time of recovery to work, the functional American Orthopaedic Foot and Ankle surgery (AOFAS) score. RESULTS: There was no significant difference in the mean operating time (72.6 ± 11.5 vs. 78.5 ± 16.4 min, P = 0.125), the time to union (21.2 ± 11.0 vs. 22.5 ± 12.3 weeks, P = 0.678), the time of recovery to work (25.0 ± 14.5 vs. 26.4 ± 13.6 weeks, P = 0.711), pin track infection (3/28 vs. 4/28, P = 1.000), delayed union (2/28 vs. 3/28, P = 1.000), pain (38.3 ± 1.6 vs. 38.7 ± 1.5, P = 0.339), function (44.4 ± 6.0 vs. 45.0 ± 5.5, P = 0.698), and total AOFAS scores (91.5 ± 7.4 vs. 93.4 ± 6.8, P = 0.322) between the two groups. However, the mean radiation time was longer in the EF + CRIF group than in the EF + LORIF group (2.0 ± 1.2 vs. 0.3 ± 0.1 min, P < 0.01). The EF + CRIF group had no wound complications while the EF + LORIF group had five wound complications, though the difference was not statistically significant (P = 0.052). Acceptable alignment was obtained in 50 patients (22 in EF + CRIF vs. 28 in EF + LORIF, P = 0.023). Two cases with EF + CRIF had a 6 degrees of recurvatum deformity and four had 6­9 degrees of valgus deformity. CONCLUSION: Our results indicated that both EF + CRIF and EF + LORIF were reliable methods in treatment of distal tibia shaft fractures. EF + CRIF had fewer wound complications and broader indications while EF + LORIF had lower radiation exposure and better alignment.