IL-21 receptor expression in human tendinopathy.

The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1ß) in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

Hypoxia: a critical regulator of early human tendinopathy.

OBJECTIVES: To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. METHODS: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. RESULTS: Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. CONCLUSION: Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.

Vancomycin Wrap for Anterior Cruciate Ligament Surgery: Molecular Insights.

BACKGROUND: The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft. PURPOSE: To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression. RESULTS: Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05). CONCLUSION: Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment. CLINICAL RELEVANCE: Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.

30-day outcomes in hip fracture patients during the COVID-19 pandemic compared to the preceding year.

AIMS: To establish if COVID-19 has worsened outcomes in patients with AO 31 A or B type hip fractures. METHODS: Retrospective analysis of prospectively collected data was performed for a five-week period from 20 March 2020 and the same time period in 2019. The primary outcome was mortality at 30 days. Secondary outcomes were COVID-19 infection, perioperative pulmonary complications, time to theatre, type of anaesthesia, operation, grade of surgeon, fracture type, postoperative intensive care admission, venous thromboembolism, dislocation, infection rates, and length of stay. RESULTS: In all, 76 patients with hip fractures were identified in each group. All patients had 30-day follow-up. There was no difference in age, sex, American Society of Anesthesiologists (ASA) classification or residence at time of injury. However, three in each group were not fit for surgery. No significant difference was found in 30-day mortality; ten patients (13%) in 2019 and 11 patients (14%) in 2020 (p = 0.341). In the 2020 cohort, ten patients tested positive for COVID-19, two (20%) of whom died. There was no significant increase in postoperative pulmonary complications. Median time to theatre was 20 hours (interquartile range (IQR) 16 to 25) in 2019 versus 23 hours (IQR 18 to 30) in 2020 (p = 0.130). Regional anaesthesia increased from 24 (33%) cases in 2019 to 46 (63%) cases in 2020, but ten (14%) required conversion to general anaesthesia. In both groups, 53 (70%) operations were done by trainees. Hemiarthroplasty for 31 B type fractures was the most common operation. No significant difference was found for intensive care admission or 30-day venous thromboembolism, dislocation or infection, or length of stay. CONCLUSION: Little information exists on mortality and complications after hip fracture during the COVID-19 pandemic. At the time of writing, no other study of outcomes in the UK has been published.Cite this article: Bone Joint Open 2020;1-7:415-419.

S100A8 & S100A9: Alarmin mediated inflammation in tendinopathy.

Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers and cellular damage. They are constitutively expressed in immune cells such as monocytes and neutrophils and their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore identifying early immune effectors is essential to understanding the pathology. Based on our previous investigations highlighting tendinopathy as an alarmin mediated pathology we sought evidence of S100A8 & A9 expression in a human model of tendinopathy and thereafter, to explore mechanisms whereby S100 proteins may regulate release of inflammatory mediators and matrix synthesis in human tenocytes. Immunohistochemistry and quantitative RT-PCR showed S100A8 & A9 expression was significantly upregulated in tendinopathic tissue compared with control. Furthermore, treating primary human tenocytes with exogenous S100A8 & A9 significantly increased protein release of IL-6, IL-8, CCL2, CCL20 and CXCL10; however, no alterations in genes associated with matrix remodelling were observed at a transcript level. We propose S100A8 & A9 participate in early pathology by modulating the stromal microenvironment and influencing the inflammatory profile observed in tendinopathy. S100A8 and S100A9 may participate in a positive feedback mechanism involving enhanced leukocyte recruitment and release of pro-inflammatory cytokines from tenocytes that perpetuates the inflammatory response within the tendon in the early stages of disease.

Unusual complication of a tattoo in an immunosuppressed patient.

Tattooing for decorative body art is becoming more popular and, as a result, so are tattoo-related complications. Patients are unlikely to discuss tattoos with medical professionals, even though these might be relevant. Long-term immunosuppressed patients are often young adults who may wish to consider tattooing. It is well recognised that immunosuppressed patients are at increased risk of infection including cutaneous mycobacterial infections. They therefore represent a group that is at a potentially higher risk of tattoo-related complications and warrant special consideration.We present the first documented case of inflammatory myopathy as a complication following tattooing in an immunosuppressed individual. This unusual case presented as distal thigh and medial knee pain and it was only after some time that a link to the tattoo was made. This serves as a reminder to consider tattoo-related complications in the differential diagnosis of unusual atraumatic musculoskeletal pain, especially in immunosuppressed individuals.

IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.

Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.

Brachial artery transection associated with closed and open dislocation of the elbow.

Acute dislocations of the elbow complicated by brachial artery involvement are rare but serious injuries. Rapid assessment and a high index of suspicion are essential to facilitate prompt treatment, as delay in diagnosis is associated with a poorer outcome. We present two cases of brachial artery transection after closed and open dislocation of the elbow, and discuss the appropriate management of such patients.

Does degree of trochlear dysplasia and position of femoral tunnel influence outcome after medial patellofemoral ligament reconstruction?

BACKGROUND: The medial patellofemoral ligament (MPFL) is the main restraining force against lateral patellar displacement. It is disrupted after patellar subluxation or dislocation. Reconstruction of the MPFL is frequently performed when nonoperative management fails and the patient experiences recurrent patellar dislocation. PURPOSE: To determine the relationship between the degree of trochlear dysplasia and femoral tunnel position and outcome after MPFL reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 68 patients (72 knees) with recurrent dislocation of the patella underwent MPFL reconstruction. The mean follow-up was 31.3 months (range, 13-72 months). Clinical and functional outcomes were recorded using the Kujala, Lysholm, and Tegner scores. Postoperative complications, participation in sporting activity, and overall patient satisfaction were determined. Radiographs were analyzed to evaluate congruence angle, lateral patellofemoral angle, patellar height, trochlear dysplasia, trochlear boss height, and position of the femoral tunnel. RESULTS: The mean Kujala, Lysholm, and Tegner scores postoperatively were 76.2, 73.8, and 3.6, respectively (n = 61). The mean congruence angle (n = 30) improved from 22.5° to 1.0° postoperatively (P = .000038), the lateral patellofemoral angle (n = 30) improved from 7.4° to 7.8° postoperatively (P = .048), and the patellar height (n = 46) using the Caton-Deschamps method improved from 1.1 to 1.0 postoperatively (P = .000016). Mild trochlear dysplasia grade A/B was found in 89% of patients (n = 54), and 11% of patients (n = 7) had severe grade C/D dysplasia. The mean distance from the anatomic insertion of the MPFL to the center of the tunnel was 9.3 mm (range, 0.5-28.2 mm), with 71.7% thought to be within 10 mm of the anatomic position defined by Schottle (n = 46). When patients with high-grade trochlear dysplasia were excluded, anatomically placed femoral tunnels demonstrated significantly better clinical scores than did tunnels not placed anatomically (Kujala score, P = .028; Lysholm score, P = .012). A multivariate logistic regression analysis also demonstrated that the distance of the femoral tunnel from the anatomic position predicted clinical outcome (Kujala score, P = .043; Lysholm score, P = .028). All of the patients with severe trochlear dysplasia (n = 7) suffered from recurrent dislocations postoperatively, compared with only 9.3% of patients (n = 5) with mild trochlear dysplasia (P = .0001). Four patients had patellar fractures postoperatively. Of patients with mild dysplasia, 83% were either very satisfied or satisfied with the outcome of their surgery compared with only 57% with severe dysplasia (P = .05). Of patients with mild trochlear dysplasia, 56% returned to sport postoperatively compared with only 43% of patients with severe trochlear dysplasia (P = .526). CONCLUSION: This study demonstrates the importance of restoration of the anatomic insertion point of the MPFL when performing MPFL reconstruction and proposes that this procedure should not be performed in isolation in patients with high-grade trochlear dysplasia.

Tibial shaft fractures in football players.

BACKGROUND: Football is officially the most popular sport in the world. In the UK, 10% of the adult population play football at least once a year. Despite this, there are few papers in the literature on tibial diaphyseal fractures in this sporting group. In addition, conflicting views on the nature of this injury exist. The purpose of this paper is to compare our experience of tibial shaft football fractures with the little available literature and identify any similarities and differences. METHODS AND RESULTS: A retrospective study of all tibial football fractures that presented to a teaching hospital was undertaken over a 5 year period from 1997 to 2001. There were 244 tibial fractures treated. 24 (9.8%) of these were football related. All patients were male with a mean age of 23 years (range 15 to 29) and shin guards were worn in 95.8% of cases. 11/24 (45.8%) were treated conservatively, 11/24 (45.8%) by Grosse Kemp intramedullary nail and 2/24 (8.3%) with plating. A difference in union times was noted, conservative 19 weeks compared to operative group 23.9 weeks (p < 0.05). Return to activity was also different in the two groups, conservative 27.6 weeks versus operative 23.3 weeks (p < 0.05). The most common fracture pattern was AO Type 42A3 in 14/24 (58.3%). A high number 19/24 (79.2%) were simple transverse or short oblique fractures. There was a low non-union rate 1/24 (4.2%) and absence of any open injury in our series. CONCLUSION: Our series compared similarly with the few reports available in the literature. However, a striking finding noted by the authors was a drop in the incidence of tibial shaft football fractures. It is likely that this is a reflection of recent compulsory FIFA regulations on shinguards as well as improvements in the design over the past decade since its introduction.