Joint injury dramatically enhances the onset of osteoarthritis (OA) and is responsible for an estimated 12% of OA. Post-traumatic arthritis (PTA) is especially common after intraarticular fracture, and no disease-modifying therapies are currently available. We hypothesized that the delivery of mesenchymal stem cells (MSCs) would prevent PTA by altering the balance of inflammation and regeneration after fracture of the mouse knee. Additionally, we examined the hypothesis that MSCs from the MRL/MpJ (MRL) “superhealer” mouse strain would show increased multilineage and therapeutic potentials as compared to those from C57BL/6 (B6) mice, as MRL mice have shown exceptional in vivo regenerative abilities. A highly purified population of MSCs was prospectively isolated from bone marrow using cell surface markers (CD45−/TER119−/PDGFRα+/Sca-1+). B6 MSCs expanded greater than 100,000 fold in three weeks when cultured at 2% oxygen and displayed greater adipogenic, osteogenic, and chondrogenic differentiation as compared to MRL MSCs. Mice receiving only a control saline injection after fracture demonstrated PTA after 8 weeks, but the delivery of 10,000 B6 or MRL MSCs to the joint prevented the development of PTA. Cytokine levels in serum and synovial fluid were affected by treatment with stem cells, including elevated systemic interleukin-10 at several time points. The delivery of MSCs did not reduce the degree of synovial inflammation but did show increased bone volume during repair. This study provides evidence that intra-articular stem cell therapy can prevent the development of PTA after fracture and has implications for possible clinical interventions after joint injury before evidence of significant OA.

Objective Obesity and joint injury are both primary risk factors for osteoarthritis (OA) that involve potential alterations in the biomechanical and inflammatory environments of the joint. Post-traumatic arthritis (PTA) is a frequent long-term complication of intra-articular fractures. Obesity has been linked to primary OA and may potentially contribute to the development of PTA by a variety of mechanisms. The objectives of this study were to determine if diet-induced obesity influences the severity of PTA in mice and to examine interrelationships between joint degeneration and serum levels of inflammatory cytokines and adipokines in this response. Methods C57BL/6 mice were fed either normal chow (13% fat) or a high-fat diet (60% fat) starting at 4 weeks of age. At 16 weeks, half of each group received closed intra-articular fracture of the left knee. At 8 weeks post-fracture, knee osteoarthritis was assessed by cartilage and synovium histology in addition to bone morphology. Serum cytokine concentrations were determined with multiplex assay. Results Fractured knee joints of mice on a high-fat diet showed significantly increased osteoarthritic degeneration compared to non-fractured contralateral controls, while fractured knee joints of low-fat mice did not demonstrate significant differences from non-fractured contralateral controls. High-fat diet increased serum concentrations of interleukin-12p70, interleukin-6, and keratinocyte-derived chemokine, while decreasing adiponectin concentrations. Systemic levels of adiponectin were inversely correlated with synovial inflammation in control limbs. Conclusion Diet-induced obesity significantly increased the severity of osteoarthritis following intra-articular fracture. Obesity and joint injury together can alter systemic levels of inflammatory cytokines such as IL-12p70.

Introduction: National trends reveal increased transfers to referral hospitals for surgical management of pediatric supracondylar humerus (SCH) fractures. This is partly because of the belief that pediatric orthopaedic surgeons (POs) deliver improved outcomes compared with nonpediatric orthopaedic surgeons (NPOs). We compared early outcomes of surgically treated SCH fractures between POs and NPOs at a single center where both groups manage these fractures. Methods: Patients ages 3 to 10 undergoing surgery for SCH fractures from 2014 to 2020 were included. Patient demographics and perioperative details were recorded. Radiographs at surgery and short-term follow-up assessed reduction. Primary outcomes were major loss of reduction (MLOR) and iatrogenic nerve injury (INI). Complications were compared between PO-treated and NPO-treated cohorts. Results: Three hundred and eleven fractures were reviewed. POs managed 132 cases, and NPOs managed 179 cases. Rate of MLOR was 1.5% among POs and 2.2% among NPOs (P = 1). Rate of INI was 0% among POs and 3.4% among NPOs (P = 0.041). All nerve palsies resolved postoperatively by mean 13.1 weeks. Rates of reoperation, infection, readmission, and open reduction were not significantly different. Operative times were decreased among POs (38.1 vs. 44.6 min; P = 0.030). Pin constructs were graded as higher quality in the PO group, with a higher mean pin spread ratio (P = 0.029), lower rate of "C" constructs (only 1 "column" engaged; P = 0.010) and less frequent crossed-pin technique (P < 0.001). Multivariate analysis revealed minimal positive associations only for operative time with MLOR (odds ratio = 1.021; P = 0.005) and INI (odds ratio = 1.048; P = 0.009).Conclusions: Postsurgical outcomes between POs and NPOs were similar. Rates of MLOR were not different between groups, despite differences in pin constructs. The NPO group experienced a marginally higher rate of INI, though all injuries resolved. Pediatric subspecialty training is not a prerequisite for successfully treating SCH fractures, and overall value of orthopaedic care may be improved by decreasing transfers for these common injuries. Level of Evidence: Level III-retrospective cohort study.

Glutamate racemase activity in Bacillus anthracis is of significant interest with respect to chemotherapeutic drug design, because L-glutamate stereoisomerization to D-glutamate is predicted to be closely associated with peptidoglycan and capsule biosynthesis, which are important for growth and virulence, respectively. In contrast to most bacteria, which harbor a single glutamate racemase gene, the genomic sequence of B. anthracis predicts two genes encoding glutamate racemases, racE1 and racE2. To evaluate whether racE1 and racE2 encode functional glutamate racemases, we cloned and expressed racE1 and racE2 in Escherichia coli. Size exclusion chromatography of the two purified recombinant proteins suggested differences in their quaternary structures, as RacE1 eluted primarily as a monomer, while RacE2 demonstrated characteristics of a higher-order species. Analysis of purified recombinant RacE1 and RacE2 revealed that the two proteins catalyze the reversible stereoisomerization of L-glutamate and D-glutamate with similar, but not identical, steady-state kinetic properties. Analysis of the pH dependence of L-glutamate stereoisomerization suggested that RacE1 and RacE2 both possess two titratable active site residues important for catalysis. Moreover, directed mutagenesis of predicted active site residues resulted in complete attenuation of the enzymatic activities of both RacE1 and RacE2. Homology modeling of RacE1 and RacE2 revealed potential differences within the active site pocket that might affect the design of inhibitory pharmacophores. These results suggest that racE1 and racE2 encode functional glutamate racemases with similar, but not identical, active site features.

Background: Selective fusions of the structural curve remain a common treatment strategy for adolescent idiopathic scoliosis, yet long-term outcomes are not well-understood. The purpose of this study was to report 10-year prospective radiographic and patient-rated outcomes of selective fusions of the main thoracic (MT) or thoracolumbar/lumbar (TL/L) curve, with particular attention to the behavior of the uninstrumented, compensatory curve. Methods: A prospectively collected multicenter database was used to identify patients who had been followed regularly for least 10 years after a selective MT or TL/L fusion for adolescent idiopathic scoliosis. Interval radiographs were evaluated for coronal and sagittal Cobb angles as well as overall coronal balance. Scores on the Scoliosis Research Society Questionnaire (SRS-24) were catalogued and evaluated. Radiographic outcomes and SRS-24 scores were compared between preoperative and postoperative time points using repeated-measures analysis of variance. Individual patient records were screened for recent curve progression of >5°, and these cases were methodically evaluated. Results: Fifty-one patients with selective fusions (21 MT and 30 TL/L) for adolescent idiopathic scoliosis who had been followed for at least 10 years were identified. The instrumented MT and TL/L curves were corrected by an average of 51% and 60%, respectively, at 10 years. The uninstrumented, compensatory curves had gradual spontaneous correction that approached the magnitude of the fused curve at 5 years postoperatively, with the correction maintained at 10 years. This led to excellent coronal balance. A subgroup of patients had recent progression of the primary curve adjacent to the prior fusion or within the instrumented segments, resulting in a compensatory progression of the uninstrumented curve. On the whole, SRS scores did not decrease during follow-up, and no patient had secondary operations. Conclusions: Selective fusion of a primary thoracic or lumbar curve in properly selected patients with adolescent idiopathic scoliosis will result in spontaneous correction of the uninstrumented curve and a durable result for at least 10 years. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Free flap reconstruction of the knee has a high flap survival and limb preservation rate in threatened extremities. Flap survival rates in the knee are similar to reported rates elsewhere in the lower extremity. Despite flap survival, infected nonunions that occur after bone free flap reconstruction result in a high limb amputation rate.

Background: The physical risk factors leading to distal radial fractures are poorly understood. The goal of this study was to compare postural stability between older adults with and without a prior distal radial fragility fracture. Methods: This case-control evaluation was performed at a single tertiary institution. The fracture cohort comprised 23 patients treated for a low-energy distal radial fracture within 6 to 24 months prior to this study. Twenty-three age and sex-matched control participants, without a prior fragility fracture, were selected from an outpatient clinic population. All participants completed a balance assessment with a computerized balance platform device. Dynamic motion analysis (DMA) scores ranging from 0 to 1,440 points are produced, with lower scores indicating better postural stability. Participants also completed validated questionnaires for general health quality (EuroQol-5D-3L [EQ-5D-3L]) and physical activity (Physical Activity Scale for the Elderly [PASE]) and comprehensive health and demographic information including treatment for compromised balance or osteoporosis. Statistical analysis compared data between cases and controls using either the Student t test or the Mann-Whitney U test. Results: There were no significant differences (p > 0.05) in age, sex, body mass index, physical activity score, or EQ-5D-3L general health visual analog scale score between participants with or without prior distal radial fracture. The fracture cohort demonstrated poorer balance, with higher DMA scores at 933 points compared with 790 points for the control cohort (p = 0.008). Nineteen patients (83%) in the fracture cohort reported having dual x-ray absorptiometry (DXA) scans within 5 years prior to this study, but only 2 patients (9%) had ever been referred for balance training with physical therapy. Conclusions: Older adults who sustain low-energy distal radial fractures demonstrate impaired postural stability compared with individuals of a similar age who have not sustained such fractures. Following a distal radial fracture, these patients may benefit from interventions to improve postural stability. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Approximately 1 in 4 patients with FAI presents with symptoms in the contralateral hip, and an additional 1 in 4 patients develops significant symptoms in the following 4 years. Several factors, including low activity level, less hip rotational motion, and decreased head-neck offset ratio, were significantly associated with the development of symptoms, while the alpha angle and crossover sign were not.