Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women.

BackgroundTrigger finger (TF), a painful condition involving a finger flexor tendon, is a common problem with a prevalence of ~2-3% in the general population. However, the TF prevalence is higher among diabetic patients-ranges from 6.7% to 10%. We have analyzed the expression of the extracellular matrix, inflammation, and epigenetic related genes in diabetic and non-diabetes TF. We hypothesized that Diabetes condition induces alter the expression of epigenetic modification genes in diabetic patients and one of the underlying determinants for more prevalence of TF in diabetic patients.MethodTissues from the fingers of patients with symptomatic trigger fingers were collected. We had three groups: carpal tunnel syndrome (as a control), trigger finger, and diabetic trigger finger. A quantitative real-time polymerase chain reaction was performed. The gene expression of Extracellular matrix (ECM) components [COL-I, COL-II, COL-X, Aggrecan], DNA methyltransferases enzymes (DNMT1, DNMT3), growth factors (TGF-b, IGF), and Histone deacetylase enzymes (HDAC1, HDAC2) were evaluated in all groups.ResultsThe mRNA expression of COL-I, COL-II, Aggrecan was significantly higher in the pully A1 of diabetic patients (p= 0.0164, p=0.0351, p=0.0399, respectively) as compared to non-diabetic TF patients. Diabetes was associated with a significant increase in the DNMT3 expression compared to non-diabetic TF patients (p=0.0485). HDAC1 and HDAC2 gene expression were up-regulated in diabetic TF than non-diabetic TF.ConclusionThe chronic state of hyperglycemia induces epigenetic modification of gene expressions in trigger fingers. This seems to have a significant impact on the development, recurrence, and progression of trigger finger in diabetic patients.

Trigger finger is a common yet vastly understudied fibroproliferative hand pathology, severely affecting patients’ quality of life. Consistent trauma due to inadequate positioning within the afflicted finger’s tendon/pulley system leads to cellular dysregulation and eventual fibrosis. While the genetic characteristics of the fibrotic tissue in the trigger finger have been studied, the pathways that govern the initiation and propagation of fibrosis are still unknown. The complete gene expression profile of the trigger finger has never been explored. Our study has used the Nanostring nCounter gene expression assay to investigate the molecular signaling involved in trigger finger pathogenesis. We collected samples from patients undergoing trigger finger (n = 4) release surgery and compared the gene expression to carpal tunnel tissue (n = 4). Nanostring nCounter analysis identified 165 genes that were differentially regulated; 145 of these genes were upregulated, whereas 20 genes were downregulated. We found that several collagen genes were significantly upregulated, and a regulatory matrix metalloproteinase (MMP), MMP-3, was downregulated. Bioinformatic analysis revealed that several known signaling pathways were dysregulated, such as the TGF-β1 and Wnt signaling pathways. We also found several novel signaling pathways (e.g., PI3K, MAPK, JAK-STAT, and Notch) differentially regulated in trigger finger. The outcome of our study helps in understanding the molecular signaling pathway involved in the pathogenesis of the trigger finger.

Introduction Distal radius fractures (DRFs) are among the most common orthopaedic injuries. The prevalence of DRFs is increasing across all age groups but remains the second most common fracture in the elderly. The modified frailty index (MFI) often predicts morbidity and mortality in orthopaedic injuries. This study aims to determine the predictive value of MFI on complication rates following DRF and the patient length of stay and discharge outcomes. Methods We utilized our MFI to perform a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Results In a total of 22,313 patients, the average age was 46 ± 16. An increase in MFI led to an increase in the odds ratio of readmission and reoperation (p < 0.001). MFI predicted complications, doubling the rate as the score increased from 1 to 2 (p < 0.001). An MFI of 2 also led to a delayed hospital stay of 5 days (p < 0.001), as well as an increase in the odds of patients not being sent home at discharge (p < 0.001). Finally, life-threatening complications were also predicted with an increased MFI, the odds of a life-threatening complication increasing 488.20 times at an MFI of 3 (p < 0.001). Discussion and Conclusion While surgical decision-making for frail patients with DRFs remains contentious, this novel 8-item MFI score was significantly associated with the probability of hospital readmission/reoperation, postoperative complications, and delayed hospital length of stay. Three new parameters were incorporated into our 8-item score compared with the conventional 5; hypoalbuminemia status (< 3.5 mg/dL), previous diagnosis of osteoporosis, and severe obesity (body mass index > 35) enhancing its sensitivity. Future studies are warranted for its prospective utility in ruling out postsurgical comorbidity.