Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced bone regeneration disorders. In summary, our findings confirm the endogenous inhibitory effect of Nr4a1 on TGF- β1 and uncover the effectiveness of Nr4a1 agonists as a therapeutic tool to improve bone regeneration, which provides a new solution strategy for the treatment of clinical bone defects and inflammatory skeletal diseases.
Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.Aims
Methods
During the pandemic of COVID-19, some patients with COVID-19 may need emergency surgeries. As spine surgeons, it is our responsibility to ensure appropriate treatment to the patients with COVID-19 and spinal diseases. A protocol for spinal surgery and related management on patients with COVID-19 has been reviewed. Patient preparation for emergency surgeries, indications, and contraindications of emergency surgeries, operating room preparation, infection control precautions and personal protective equipments (PPE), anesthesia management, intraoperative procedures, postoperative management, medical waste disposal, and surveillance of healthcare workers were reviewed. It should be safe for surgeons with PPE of protection level 2 to perform spinal surgeries on patients with COVID-19. Standardized and careful surgical procedures should be necessary to reduce the exposure to COVID-19.
Obesity has previously been demonstrated to be an independent risk factor for increased complications following total hip (THA) and total knee arthroplasty (TKA). The purpose of this study was to compare the effects of obesity and BMI to determine whether the magnitude of the effect was similar for both procedures. We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to identify patients who underwent primary THA or TKA between 2010 and 2014. Patients were stratified by procedure and classified as non-obese, obese, or morbidly obese according to BMI. Thirty-day rates of wound complications, deep infection, total complications, and reoperation were compared using univariate and multivariate logistic regression analyses.Purpose
Materials & Methods
Obesity has previously been demonstrated to be an independent risk factor for increased complications following total hip (THA) and total knee arthroplasty (TKA). The purpose of this study was to compare the effects of obesity and BMI to determine whether the magnitude of the effect was similar for both procedures. We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to identify patients who underwent primary THA or TKA between 2010 and 2014. Patients were stratified by procedure and classified as non-obese, obese, or morbidly obese according to BMI. Thirty-day rates of wound complications, deep infection, total complications, and reoperation were compared using univariate and multivariate logistic regression analyses. We identified 64,648 patients who underwent THA and 97,137 patients who underwent TKA. Obese THA patients had significantly higher rates of wound complications (1.53% vs 0.96%), deep infection (0.31% vs 0.17%), reoperation rate (2.11% vs 1.02%), and total complications (5.22% vs. 4.63%) compared to TKA patients. Morbidly obese patients undergoing THA were also found to have significantly higher rates of wound complications (3.25% vs 1.52%), deep infection (0.84% vs 0.23%), reoperation rate (3.65% vs 1.60%), and total complications (7.36% vs. 5.57%). Multivariate regression analysis identified increasingly higher odds of each outcome measure as BMI increased. This study demonstrates the impact of obesity on postoperative complications is more profound for THA than TKA. This emphasizes the importance of considering patient comorbidities in the context of the specific procedure (hips and knees should be analyzed independently) when assessing risks of surgery.
Fracture around the knee can lead to posttraumatic osteoarthritis (PTOA) of the knee. Malunion, malalignment, intra-articular osseous defects, retained internal fixation devices, and compromised soft tissues may affect the outcome of total knee replacement (TKR). On average, the posttraumatic patient subsets were 10.4 years younger than those for primary knee OA. Recently, there were several studies reporting the outcome of THA for posttraumatic OA hip. However, no current literature defines the comparative functional outcome between PTOA and primary OA knee. The purpose of our study was to compare the midterm outcomes of patients undergoing TKR following periarticular knee fractures/ligamentous injuries versus primary osteoarthritis (PO) of the knee. Retrospective chart reviews of patients underwent TKR between 2008 and 2013 were identified. 136 patients underwent open reduction and internal fixation with plate and screws or ligament reconstruction while 716 patients were primary OA. Mean follow up time was comparable in both groups. Demographic data, medical comorbidities, WOMAC, visual analogue scale, and complications were recorded.Introduction
Materials and methods
Readmission following any total joint arthroplasty has become a closely watched metric for many hospitals in the United States because financial penalties imposed by CMS for excessive readmissions occurring within thirty days of discharge has occurred since 2015. The purpose of this study was to identify both preoperative comorbidities associated with and postoperative reasons for readmission within thirty days following primary total joint arthroplasty in the lower extremity. Retrospective data was collected for patients who underwent elective primary total hip arthroplasty (CPT code 27130), total knee arthroplasty (27447), and total ankle arthroplasty (27702) from January 1, 2008, to December 31, 2013 at our institution. The sample was separated into readmitted and non-readmitted cohorts. Demographic variables, preoperative comorbidities, Charlson Comorbidities Index (CCI), operative parameters, readmission rates, and causes of readmission were compared between the groups using univariate and multivariate regression analysis.Background
Methods
Readmission following any total joint arthroplasty has become a closely watched metric for many hospitals in the United States because financial penalties imposed by CMS for excessive readmissions occurring within thirty days of discharge will be forthcoming in 2015. The purpose of this study was to identify both preoperative comorbidities associated with and postoperative reasons for readmission within thirty days following primary total joint arthroplasty in the lower extremity. Retrospective data was collected for patients who underwent elective primary total hip arthroplasty (CPT code 27130), total knee arthroplasty (27447), and total ankle arthroplasty (27702) from January 1, 2008, to December 31, 2013 at our institution. The sample was separated into readmitted and non-readmitted cohorts. Demographic variables, preoperative comorbidities, Charlson Comorbidities Index (CCI), operative parameters, readmission rates, and causes of readmission were compared between the groups using univariate and multivariate regression analysis.Background
Methods
Circulating exosomes represent novel biomarkers for multiple diseases. In this study, we investigated whether circulating exosome levels could be used as a diagnostic biomarker for steroid-induced osteonecrosis of the femoral head (ONFH). We assessed the serum exosome level of 85 patients with steroid-induced ONFH and 115 healthy donors by Nanosight detection. We then assessed the diagnostic accuracy of serum exosomes by receiver operating characteristic curve analysis.Objectives
Methods
The first 101 posterior cruciate retaining modular tibial components of a single design performed by a single surgeon in 75 patients were evaluated at a minimum 20-year follow-up. All components were fixed with cement. These patients had been prospectively followed at five-year intervals and evaluated clinically using Knee Society ratings and documenting any need for reoperation. Serial radiographs were evaluated for radiolucencies, osteolysis or component migration until the time of patient death or at minimum 20-year follow-up. At minimum 20-year follow-up, five knees (5%) had required a revision operation. All revisions occurred greater than 10 years following the index procedures. Benefits of modularity (i.e. retention of the tibial tray) were utilized in three of five cases in this closely followed cohort. Survivorship from any revision was 90.8% at 20 years. For the 16 living patients with 22 knees, the average Knee Society Clinical and Functional scores were 91 and 59, respectively, and the average range of motion was 115 degrees. When considering gamma irradiated in air polyethylene and a first generation locking mechanism were utilized, these results encourage the authors to continue to use modular tibial trays.
