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Trauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra‐articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug‐loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra‐articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post‐traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2949–2955, 2018. Trauma, surgery, and inflammatory diseases can cause joint contractures. We investigated the therapeutic potential of rosiglitazone‐loaded oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. Scaffolds were implanted into 12 rabbits that received rosiglitazone‐loaded hydrogels and 12 that received vehicle‐loaded hydrogels. After 8 weeks of joint immobilization, rabbits remobilized for 16 weeks. Flexion contractures treated with rosiglitazone significantly improved compared to controls. Intra‐articular delivery of rosiglitazone via OPF hydrogels improves contractures without any notable adverse effects. [ABSTRACT FROM AUTHOR]

Background: The use of chemoprophylaxis to prevent thromboembolic disease after primary THA and TKA can be associated with postoperative bleeding complications. Mechanical prophylaxis has been studied as an alternative to chemoprophylaxis with greater safety in patients undergoing THA, but no data have been published comparing the safety of chemoprophylaxis versus mechanical methods for patients undergoing TKA. The risk of readmission resulting from bleeding and venous thromboembolism (VTE) has also not been determined for patients undergoing THA or TKA when treated with low-molecular-weight heparin (LMWH) alone compared with mechanical prophylaxis plus aspirin (ASA).Question/purposes: We sought to answer four questions: For the THA and TKA cohorts, respectively, (1) was the incidence of readmission resulting from VTE and bleeding complications higher with LMWH than mobile compression plus ASA; and (2) was the incidence of wound bleeding complications higher with LMWH than mechanical compression plus ASA? For the TKA cohort specifically, (3) was the frequency of systemic bleeding events and complications related to chemical prophylaxis higher with LMWH compared with mechanical compression plus ASA? (4) Was there a difference in symptomatic VTEs between LMWH and mechanical compression plus ASA?Methods: Between November 2008 and April 2011, 632 patients underwent primary THA and TKA. Seventy-two patients (11%) were identified before surgery as being at high risk for VTE (31 patients) or bleeding (41 patients) and were excluded from the study. Five hundred sixty patients (89%) were considered to be at standard risk for VTE and bleeding and comprise the study cohort. Between November 2008 and November 2009, 252 patients (76 THAs, 176 TKAs) underwent THA and TKA and were treated with LMWH (5 mg dalteparin given subcutaneously daily for 14 days) and in-hospital nonmobile mechanical compression. Between November 2009 and April 2011, a total of 308 patients undergoing THA and TKA (108 THAs, 200 TKAs) were treated using a mobile compression device plus oral aspirin once daily for 2 weeks after surgery. All complications and readmissions that occurred within 6 weeks of surgery were noted. There were no differences between the VTE treatment groups with regard to age, sex, or body mass index.Results: For the THA cohort, there was no difference in the frequency of readmission for a bleeding complication (wound or systemic) between the two groups (2.6% for LMWH versus 0.9% for mobile compression; p = 0.57; odds ratio [OR], 2.9). Patients undergoing TKA treated with LMWH had higher readmission rates within 6 weeks of surgery because of a bleeding complication, a wound infection, or the development of a VTE (6.8% for LMWH versus 1.5% for mobile compression; p = 0.015; OR, 4.8). For the THA cohort, there was higher wound bleeding complication frequency with LMWH (9.2% for LMWH versus 0.9% for mechanical compression; p = 0.009; OR, 10.9). Patients undergoing TKA treated with LMWH had a higher frequency of wound bleeding complications or infection (3.9% for LMWH versus 0.5% for mobile compression; p = 0.028; OR, 8.2). Patients undergoing TKA treated with LMWH had higher rates of systemic bleeding or a complication secondary to LMWH administration (2.8% for LMWH versus 0% for mobile compression; p = 0.022; OR, 12.8). No difference was noted in the rate of symptomatic VTEs between either group (for THA: 2.6% for the LMWH group versus 1.9% for the mechanical compression group; p = 1; for TKA: 1.1% versus 0%, respectively; p = 0.22).Conclusions: Based on these results, we advocate for routine use of mobile mechanical compression devices in the prevention of VTEs and complications associated with more potent chemical anticoagulants. However, more focused randomized clinical trials are needed to validate these findings.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Dupuytren's disease is an inherited disorder in which patients develop fibrotic contractures of the hand. Current treatment strategies include surgical excision or enzymatic digestion of fibrotic tissue. MicroRNAs, which are key posttranscriptional regulators of genes expression, have been shown to play an important regulatory role in disorders of fibrosis. Therefore in this investigation, we apply high throughput next generation RNA sequencing strategies to characterize microRNA expression in diseased and healthy palmar fascia to elucidate molecular mechanisms responsible for pathogenic fibrosis. Methods: We applied high throughput RNA sequencing techniques to quantify the expression of all known human microRNAs in Dupuytren's and control palmar fascia. MicroRNAs that were differentially expressed between diseased and healthy tissue samples were used for computational target prediction using the bioinformatics tool ComiR. Molecular pathways that were predicted to be differentially expressed based on computational analysis were validated by performing RT-qPCR on RNA extracted from diseased and non-diseased palmar fascia biopsies. Results: A comparison of microRNAs expressed in Dupuytren's fascia and control fascia identified 74 microRNAs with a 2-fold enrichment in Dupuytren's tissue, and 32 microRNAs with enrichment in control fascia. Computational target prediction for differentially expressed microRNAs indicated preferential targeting of collagens and extracellular matrix related proteins in control palmar fascia. RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues. Discussion: Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia. Thus alterations in microRNA regulatory networks may play an important role in driving the pathogenic fibrosis seen in Dupuytren's disease via direct regulatory effects on extracellular matrix protein synthesis. Conclusion: Dupuytren's fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins. [ABSTRACT FROM AUTHOR]

Background: We observed isolated tibial component debonding from the cement in one modern primary TKA design (NexGen LPS 3° tibial tray; Zimmer, Warsaw, IN, USA). This failure mechanism is sparsely reported in the literature. Questions/Purposes: We (1) assessed survivorship of this tibial tray with special emphasis on debonding; (2) described clinical and radiographic features associated with tibial failure; and (3) compared patient and radiographic features of the failures with a matched cohort. Methods: A total of 1337 primary TKAs were performed with a cemented NexGen LPS 3° tibial tray over an 11-year period. Twenty-five knees (1.9%) were revised for tibial debonding. BMI and radiographic alignment in the tibial debonding group were compared with a matched control group. Implant survivorship was assessed using tibial debonding as the end point. Results: Survival free of revision from tibial debonding was 100% at 1 year and 97.8% at 5 years. The tibial failures shared a typical radiographic pattern with debonding at the cement-implant interface and subsidence into varus and flexion. We found no link between limb alignment or individual component alignment and failure because 22 of the 25 failures occurred in well-aligned knees. Conclusions: Our standardized followup of patients undergoing TKA at routine intervals allowed us to discover a higher rate of revision resulting from tibial debonding. We have discontinued the use of this particular tibial tray for primary TKA and surveillance for patients undergoing TKA continues to be warranted. Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Cementation of a constrained liner is a viable option for treating instability after total hip arthroplasty (THA) when the acetabular component is well fixed and well aligned. However, concerns regarding long-term mechanical failure and recurrent instability remain. The aim of this study was to evaluate the long-term survivorship, complications, and clinical and radiographic outcomes of constrained polyethylene liners cemented into well-fixed acetabular components at the time of revision THA.Methods: We identified 125 cases in which a constrained liner of 1 design was cemented into a retained, osseointegrated acetabular component during revision THA between 1998 and 2006. The mean patient age at revision was 70 years. Mean follow-up was 7 years. Survivorship data, risk of instability, and clinical and radiographic outcomes were analyzed.Results: Survivorship free from revision for instability was 86% at 5 years and 81% at 10 years. Survivorship free from aseptic acetabular component revision was 78% at 5 years and 65% at 10 years, with the most common failure mechanism being dissociation of the constrained liner from the acetabular component. Survivorship free from revision for any reason was 76% at 5 years and 60% at 10 years. The most common complications were instability and periprosthetic joint infection, with cumulative incidences at 7 years of 18% and 11%, respectively. Harris hip scores did not significantly improve. Cup position did not affect implant survivorship or risk of dislocation.Conclusions: Cementing a constrained liner into a retained acetabular shell at the time of revision THA has durable long-term results, with 8 in 10 patients free from instability at 10 years. Aseptic acetabular survivorship was worse (65%) at 10 years, primarily due to dissociation of the constrained liner from the acetabular component.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Case: A 43-year-old woman with dermatomyositis presented with Mycobacterium avium complex (MAC) knee septic arthritis with superimposed polymicrobial infection. After poor infection control with antibiotic therapy, she underwent debridement and antibiotic cement spacer placement, followed by knee arthrodesis 6 months later. At 2-year follow-up, she had no pain and was ambulating without assistive devices. Conclusion: As far as we know, this is the first reported case of MAC native-knee septic arthritis successfully treated with antibiotic cement spacer followed by knee arthrodesis. This case sheds insight on treatment strategies for a rare native-knee infection. [ABSTRACT FROM AUTHOR]