Assessment of the effectiveness of weight-adjusted antibiotic administration, for reduced duration, in surgical prophylaxis of primary hip and knee arthroplasty.

BACKGROUND: Prophylactic antibiotics have significantly led to a reduction in the risk of post-operative surgical site infections (SSI) in orthopaedic surgery. The aim of using antibiotics for this purpose is to achieve serum and tissue drug levels that exceed, for the duration of the operation, the minimum inhibitory concentration of the likely organisms that are encountered. Prophylactic antibiotics reduce the rate of SSIs in lower limb arthroplasty from between 4% and 8% to between 1% and 3%. Controversy, however, still surrounds the optimal frequency and dosing of antibiotic administration. AIM: To evaluate the impact of introduction of a weight-adjusted antibiotic prophylaxis regime, combined with a reduction in the duration of administration of post-operative antibiotics on SSI incidence during the 2 years following primary elective total hip and knee arthroplasty. METHODS: Following ethical approval, patients undergoing primary total hip arthroplasty (THA)/total knee arthroplasty (TKA) with the old regime (OR) of a preoperative dose [cefazolin 2 g intravenously (IV)], and two subsequent doses (2 h and 8 h), were compared to those after a change to a new regime (NR) of a weight-adjusted preoperative dose (cefazolin 2 g IV for patients < 120 kg; cefazolin 3g IV for patients > 120 kg) and a post-operative dose at 2 h. The primary outcome in both groups was SSI rates during the 2 years post-operatively. RESULTS: A total of n = 1273 operations (THA n = 534, TKA n = 739) were performed in n = 1264 patients. There was no statistically significant difference in the rate of deep (OR 0.74% (5/675) vs NR 0.50% (3/598); fishers exact test P = 0.72), nor superficial SSIs (OR 2.07% (14/675) vs NR 1.50% (9/598); chi-squared test P = 0.44) at 2 years post-operatively. With propensity score weighting and an interrupted time series analysis, there was also no difference in SSI rates between both groups [RR 0.88 (95%CI 0.61 to 1.30) P = 0.46]. CONCLUSION: A weight-adjusted regime, with a reduction in number of post-operative doses had no adverse impact on SSI incidence in this population.

Midterm outcome of superior capsular reconstruction using doubled acellular human dermal allograft for irreparable rotator cuff tear.

BACKGROUND: Thicker (folded) facia lata autografts have been shown to be superior to thinner grafts and single-layered acellular human dermal (HD) allografts for superior capsular reconstruction (SCR) in biomechanical studies. The aim of this study was to evaluate the midterm clinical outcomes following SCR for irreparable supraspinatus tears using doubled (folded) HD allograft. METHODS: Thirty-two patients who had undergone SCR using doubled HD allograft between February 2012 and January 2020 were recruited in a continuous manner in this retrospective study. The inclusion criteria were SCR performed for irreparable supraspinatus tear and a minimum of 2 years' follow-up. The primary outcome measure was the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score. The secondary outcome measures were complications and revision surgery. A subgroup analysis was performed between patients who received a "standard" graft of mean 3-mm thickness or a "thick" graft of mean 4.4-mm thickness. RESULTS: One patient was lost to follow-up. A total of 31 patients (31 shoulder joints) were analyzed with a mean follow-up duration of 48 months (range, 25-96 months). Following surgery, there was significant improvement in the ASES score from 18.1 ± 14.3 (preoperative) to 76.3 ± 25.1 (postoperative) (P < .001), with a satisfactory clinical outcome obtained in 83.8% of the patients. In a subset of 8 patients completing 5 years' follow-up, the clinical improvements were sustained. The percentage of patients with a clinically successful outcome was higher among those with thick grafts compared to those with standard grafts, although this failed to reach statistical significance (94.4% vs. 69.2%, risk ratio 1.36, 95% confidence interval 0.93-1.99, P = .13). One patient within the standard group underwent revision surgery. CONCLUSION: SCR for irreparable rotator cuff tears with doubled HD allograft results in improved clinical outcomes and low reoperation at midterm follow-up duration.

Circumferential Periosteal Release to Treat Paediatric Leg Length Discrepancy: Medium Term Outcomes.

Aims: This study aims to report the medium term outcomes of circumferential periosteal release of the distal femur and distal tibia in treating paediatric leg length discrepancy (LLD). Materials and methods: A retrospective case series was performed on all patients undergoing circumferential periosteal release of the distal femur and/or tibia between 2006 and 2019. Data collected included demographics, surgical indications, post-operative leg lengths, and complications. Leg length discrepancy was calculated as actual values and percentages of the longest limb length. Final actual and percentage discrepancies were compared to initial discrepancies using a paired t-test. Patterns of discrepancy over time were analysed using linear mixed models. Results: Eighteen patients (11 males) were identified, who underwent 25 procedures. The mean age at first surgery was 5.8 (range, 2-13). The commonest indication was congenital limb deficiency (7 patients). Five patients underwent repeat periosteal release, and one patient had three releases. The mean follow-up was 63 months [standard deviation (SD), 33.9]. Fifteen patients had sufficient data for statistical analysis.The mean actual discrepancy decreased from 2.07 cm (SD, 1.07) to 1.12 cm (SD, 1.62), and the mean relative discrepancy from 4.3% (SD, 2.8) to 1.5% (SD, 2.4). Significant mean reductions were seen in both actual discrepancies [0.61 cm (95% CI: 0.05-1.16; p = 0.034)], and percentage discrepancy [2.10% (95% CI: 1.0-3.1, p = <0.001]). In five patients, the operated limb overgrew the contralateral limb. Patients whose operated limb overgrew still had a reduction in LLD, with a mean residual discrepancy less than 1 cm (mean 0.7 cm, 95% CI: From -0.9 to 2.4). Conclusion: Circumferential periosteal release produces a significant decrease in both actual and percentage LLD. We believe this procedure is best indicated in younger patients with congenital LLD in whom the discrepancy is predicted to increase as they age. Clinical significance: Circumferential periosteal release produces a significant decrease in LLD. This procedure can be used to manage symptoms during growth, particularly at the point where orthotic usage may become problematic, and to potentially reduce the magnitude of surgery needed at an older age. How to cite this article: Chatterton BD, Kuiper JH, Williams DP. Circumferential Periosteal Release to Treat Paediatric Leg Length Discrepancy: Medium Term Outcomes. Strategies Trauma Limb Reconstr 2023;18(2):67-72.

Comparison of Knee Articular Cartilage Defect Size Between Measurements Obtained on Preoperative MRI Versus During Arthrotomy.

Background: Treatment decisions for cartilage defects are often based on lesion size. Magnetic resonance imaging (MRI) is widely used to diagnose cartilage defects noninvasively; however, their size estimated from MRI may differ from defect sizes measured during arthrotomy, especially after debridement to healthy cartilage if undergoing autologous chondrocyte implantation. Purpose/Hypothesis: The purpose of this study was to evaluate the reliability of 2 methods to assess knee cartilage defect size on preoperative MRI and determine their accuracy in predicting postdebridement defect sizes recorded during arthrotomy. It was hypothesized that defect size would be predicted more accurately by the total area of abnormal articular cartilage rather than the area of full-thickness cartilage loss as identified on MRI. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: This study included 64 patients (mean age, 41.8 ± 9.6 years) who underwent autologous cell therapy. Each patient received a 3-T MRI at 6.1 ± 3.0 weeks before cell implantation. Three raters, a radiologist, a surgeon, and a scientist, measured (1) the full-thickness cartilage defect area and (2) the total predicted abnormal cartilage area, identified by an abnormal signal on MRI. Interrater reliability was assessed using the intraclass correlation coefficient (ICC). Actual pre- and postdebridement defect sizes were obtained from intraoperative surgical notes. Postdebridement surgical measurements were considered the clinical reference standard and were compared with the radiologist's MRI measurements. Results: Eighty-seven defects were assessed, located on the lateral (n = 8) and medial (n = 26) femoral condyle, trochlea (n = 17), and patella (n = 36). The interrater reliability of the cartilage defect measurements on MRI was good to excellent for the full-thickness cartilage defect area (ICC = 0.74) and the total predicted abnormal cartilage area (ICC = 0.78). The median full-thickness cartilage defect area on MRI underestimated the median postdebridement defect area by 78.3%, whereas the total predicted abnormal cartilage area measurement underestimated the postdebridement defect area by 14.3%. Conclusion: Measuring the full-thickness cartilage defect area on MRI underestimated the area to treat, whereas measuring the total abnormal area provided a better estimate of the actual defect size for treatment.

A pilot randomised controlled trial assessing standard versus dermal patch-augmented rotator cuff repair found no adverse effects and suggest future trials need a minimum of 150 patients.

PURPOSE: The aims of this pilot randomised controlled trial (RCT) were to assess the safety and efficacy of a human dermal allograft patch and assess the feasibility of a future RCT comparing retear rate and functional outcome 12 months following standard and augmented double-row rotator cuff repair. METHODS:  A pilot RCT was conducted among patients undergoing arthroscopic repair of rotator cuff tear measuring between 1 and 5 cm. They were randomised to either augmented (double-row repair with human acellular dermal patch) or standard (double-row repair only). The primary outcome was rotator cuff retear determined on MRI scan at 12 months using the Sugaya's classification (grade 4 or 5). All adverse events were recorded. Functional assessment was performed at baseline and 3, 6, 9, and 12 months post-surgery using clinical outcome scores. Safety was assessed by complications and adverse effects, and feasibility by recruitment, follow-up rate and proof of concept statistical analyses of a future trial. RESULTS: Between 2017 and 2019, 63 patients were considered for inclusion. Twenty-three patients were excluded, leaving 40 patients (20 per group) in the final study population. The mean tear sizes were 3.0 cm in the augmented and 2.4 cm in the standard group. There was one adhesive capsulitis in the augmented group, with no other adverse events. Retear was observed in 4/18 (22%) of patients in the augmented and 5/18 (28%) in the standard group. In both groups, functional outcome improved significantly which was clinically meaningful for all scores, with no difference between groups. Retear rate increased with tear size. Future trials are feasible but need a minimum total sample size of 150 patients. CONCLUSION:  Clinically meaningful improved function without adverse effects was found with human acellular dermal patch-augmented cuff repairs. LEVEL OF EVIDENCE: Level II.

Relationship Between Activity Level and Knee Function Is Influenced by Negative Affect in Patients Undergoing Cell Therapy for Articular Cartilage Defects in the Knee.

Background: Increased activity level is generally reported to be positively related to improved knee function after knee surgery. However, little research has been conducted into this relationship on an individual patient basis, or the influence of demographic and psychosocial factors such as patient affect-the subjective experience of emotion. Hypothesis: The relationship between postoperative activity level and knee function will vary between patients and will be influenced by the patients' affect and demographic characteristics. Study Design: Cohort study; Level of evidence, 3. Methods: Activity, knee function, demographic, and affect data were collected from patients enrolled in an ongoing trial for the treatment of articular cartilage lesions at preoperative and 2-, 12-, and 15-month postoperative points. Quantile mixed regression modeling was used to determine the patient-to-patient variation in activity level and knee function. Multiple linear regression and partial correlation analyses were performed to determine whether demographic characteristics and patient affect were associated with this variation. Results: A total of 62 patients were included in the study (23 female; 39 male; mean age, 38.3 ± 9.5 years). We found substantial variation between patients in the relationship between activity level and knee function, with most patients (n = 56) demonstrating a positive relation (positive slope), but 6 patients demonstrating a negative relation (negative slope). A negative affect (NA) score was significantly correlated with the slope between activity level and knee function (r S = -0.30; P = .018) and was a significant individual predictor of knee function at 15 months postoperatively (coefficient = -3.5; P = .025). Conclusion: Our results suggest that the relationship between activity level and knee function varies between patients. The patients with a higher NA score were likely to report smaller improvements in knee function with increasing activity levels compared with those with a lower NA score.

A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee.

BACKGROUND: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. PURPOSE: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. RESULTS: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, -1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, -0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). CONCLUSION: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. REGISTRATION: International Standard Randomised Controlled Trial Number: 48911177.

Histological and Radiological Assessment of Endogenously Generated Repair Tissue In Vivo Following a Chondral Harvest.

OBJECTIVE: To examine repair tissue formed approximately 15 months after a chondral harvest in the human knee. DESIGN: Sixteen individuals (12 males, 4 females, mean age 36 ± 9 years) underwent a chondral harvest in the trochlea as a pre-requisite for autologous chondrocyte implantation (ACI) treatment. The harvest site was assessed via MRI at 14.3 ± 3.2 months and arthroscopy at 15 ± 3.5 months (using the Oswestry Arthroscopy Score [O-AS] and the International Cartilage Repair Society Arthroscopy Score [ICRS-AS]). Core biopsies (1.8 mm diameter, n = 16) of repair tissue obtained at arthroscopy were assessed histologically (using the ICRS II and OsScore histology scores) and examined via immunohistochemistry for the presence of collagen types I and II. RESULTS: The mean O-AS and ICRS-AS of the repaired harvest sites were 7.2 ± 3.2 and 10.1 ± 3.5, respectively, with 80.3% ± 26% repair fill depth on MRI. The histological quality of the repair tissue formed was variable, with some hyaline cartilage present in 50% of the biopsies; where this occurred, it was associated with a significantly higher ICRS-AS than those with no hyaline cartilage present (median 11 vs. 7.5, P = 0.049). Collagen types I and II were detected in 12/14 and 10/13 biopsies, respectively. CONCLUSIONS: We demonstrate good-quality structural repair tissue formed following cartilage harvest in ACI, suggesting this site can be useful to study endogenous cartilage repair in humans. The trochlea is less commonly affected by osteoarthritis; therefore, location may be critical for spontaneous repair. Understanding the mechanisms and factors influencing this could improve future treatments for cartilage defects.

Greater trochanteric pain syndrome: focused shockwave therapy versus an ultrasound guided injection: a randomised control trial.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) is a common problem with an incidence of 1.8-5.6 per 1000 population. Physiotherapy, anti-inflammatories, corticosteroid injections and surgery have all been described in the management of GTPS, with limited, temporal success. Extracorporeal shockwave therapy (ESWT) has been proposed as a potential non-invasive management option for this difficult presentation. METHOD: We ran a prospective, 2-arm, single-blinded, randomised control trial comparing focused shockwave therapy (f-ESWT) to an ultrasound guided corticosteroid injection. Primary outcome measure was the visual analogue pain score. Secondary outcome measures included the Harris Hip Score (HHS) and Trendelenburg test for function; SF-36 for quality of life (QoL); and a Likert scale question for subjective assessment of symptom improvement. RESULTS: 104 patients (10 males and 94 females), of mean age 61.5 years were recruited. 53 were randomised to receive ESWT and 51 to receive an image-guided injection. 11 patients were lost to follow-up. There were no significant differences in baseline scores between groups.At 3 months, pain, function and QoL scores had improved in both groups but were not statistically significant. The Trendelenburg test was significantly improved in the f-ESWT group with 80% patients being negative compared to 20% at baseline (p < 0.001).At 12 months, across all outcomes, the ESWT group had significantly improved scores compared to the injection group; VAS 37.1 versus 55.0 (p = 0.007, 95% confidence interval [CI], 6.3-30.8), HHS 69.7 versus 57.5 (p = 0.002, 95% CI, -20.0 to -4.6) and SF-36 52.4 versus 47.7 (p = 0.048, 95% CI, -9.31 to -0.04). The improvement in Trendelenburg test was maintained in the ESWT group, but the injection group had reverted to baseline (p < 0.001). CONCLUSIONS: We have shown f-ESWT is an effective treatment for patients with GTPS. We would advocate f-ESWT as an effective non-invasive treatment modality for this challenging patient population.Trial Registration No. ISRCTN8338223.

Evaluating the Feasibility and Reliability of Remotely Delivering and Scoring the North Star Ambulatory Assessment in Ambulant Patients with Duchenne Muscular Dystrophy.

OBJECTIVE: The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD). The SARS-CoV-2 pandemic and subsequent Government 'lockdown' resulted in no face-to-face clinic visits hence the motor abilities were not monitored. The aim was to investigate whether the NSAA was feasible and reliable by video assessment. METHOD: Ten ambulant DMD boys were selected from the electronic hospital records. Two physiotherapists scored the boys' NSAA independently and the intraclass correlation coefficient was used to assess agreement. The video scores were compared to two previous NSAA in-clinic scores. RESULTS: Mean scores (SD) for clinic visit one were 22.6 (4.19) and clinic visit two 21.8 (5.3). The two physiotherapists video mean scores were 20.6 (5.66) for physiotherapist 1 and 20.6 (6.53) for physiotherapist 2. The intraclass correlation coefficient was 0.98 (95% CI 0.93-1.00) for the total NSAA and 1.00 (95% CI 1.00 to 1.00) for the rise time. The mean decline in score from clinic visit one (-12 months) to video assessment was 2.0 (2.8SD). CONCLUSION: The results from the study suggest that video NSAA is partially feasible and reliable.

Osteochondral Lesions of the Ankle Treated with Bone Marrow Concentrate with Hyaluronan and Fibrin: A Single-Centre Study.

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months.

Clinical validation of the Oswestry-Bristol Classification as part of a decision algorithm for trochlear dysplasia surgery.

AIMS: The Oswestry-Bristol Classification (OBC) is an MRI-specific assessment tool to grade trochlear dysplasia. The aim of this study is to validate clinically the OBC by demonstrating its use in selecting treatments that are safe and effective. METHODS: The OBC and the patellotrochlear index were used as part of the Oswestry Patellotrochlear Algorithm (OPTA) to guide the surgical treatment of patients with patellar instability. Patients were assigned to one of four treatment groups: medial patellofemoral ligament reconstruction (MPFLr); MPFLr + tibial tubercle distalization (TTD); trochleoplasty; or trochleoplasty + TTD. A prospective analysis of a longitudinal patellofemoral database was performed. Between 2012 and 2018, 202 patients (233 knees) with a mean age of 24.2 years (SD 8.1), with recurrent patellar instability were treated by two fellowship-trained consultant sports/knee surgeons at The Robert Jones and Agnes Hunt Orthopaedic Hospital. Clinical efficacy of each treatment group was assessed by Kujala, International Knee Documentation Committee (IKDC), and EuroQol five-dimension questionnaire (EQ-5D) scores at baseline, and up to 60 months postoperatively. Their safety was assessed by complication rate and requirement for further surgery. The pattern of clinical outcome over time was analyzed using mixed regression modelling. RESULTS: In all, 135 knees (mean age 24.9 years (SD 9.4)) were treated using a MPFLr. Ten knees (7.4%) required additional surgery. A total of 50 knees (mean age 24.4 years (SD 6.3)) were treated using MPFLr + TTD. Ten (20%) required additional surgery. A total of 20 knees (mean age 19.5 years (SD 3.0)) were treated using trochleoplasty + TTD. Three patients (15%) required additional surgery. In each treatment group, there was a significant improvement in Kujala, IKDC, and EQ-5D at one year postoperatively (p < 0.001) with a recognized level of overall complication rate. CONCLUSION: The OBC is a valid assessment tool to grade patients with trochlear dysplasia and, when used as part of the OPTA, helps to determine treatments that are safe and effective. This fulfils the requirements for its application in mainstream clinical practice. Cite this article: Bone Joint J 2021;103-B(10):1586-1594.

Contralateral strength training attenuates muscle performance loss following anterior cruciate ligament (ACL) reconstruction: a randomised-controlled trial.

PURPOSE: To investigate the effects of cross-education (CE) exercise on strength and performance at 10 and 24 weeks post anterior cruciate ligament (ACL) surgery. METHODS: Design: randomised controlled trial. N = 44 ACL-reconstruction patients, randomly-allocated into: CE: strength training of the non-operative limb, or CON: sham exercise of upper limb stretching. Each patient underwent standardised ACL rehabilitation, plus 8 weeks of thrice weekly CE or CON, commencing at 2 weeks post surgery. The primary outcome was quadriceps peak force (QPF) of the ACL-reconstructed limb at 10 weeks post surgery. Secondary measures were hamstrings peak force (HPF), rate of force development (RFD) and International Knee Documentation Committee score (IKDC) at 10 and 24 weeks; QPF and hop for distance (HOP) at 24 weeks post surgery. RESULTS: CE significantly attenuated the decline in QPF of the ACL-reconstructed limb at 10 weeks compared to CON (16.6% decrease vs. 32.0%, respectively); that advantage was not retained at 24 weeks. A training effect was observed in the trained limb for HPF and QPF, which was retained at 24 weeks. No significant differences were observed for IKDC, HOP, RFD, or HPF of the reconstructed limb. Inter-limb symmetry (ILS) ranged from 0.78 to 0.89 and was not significantly different between groups. CONCLUSION: High-intensity CE strength training attenuated the post-operative decline in QPF and should be considered in early-phase ACL rehabilitation. ILS data showed good symmetry, but it masked significantly inferior performance between groups and should be used with caution. TRIAL REGISTRATION NUMBER: NCT02722876.

An In Vitro System to Study the Effect of Subchondral Bone Health on Articular Cartilage Repair in Humans.

Chondrocyte-based cartilage repair strategies, such as articular chondrocyte implantation, are widely used, but few studies addressed the communication between native subchondral bone cells and the transplanted chondrocytes. An indirect co-culture model was developed, representing a chondrocyte/scaffold-construct repair of a cartilage defect adjoining bone, where the bone could have varying degrees of degeneration. Human BM-MSCs were isolated from two areas of subchondral bone in each of five osteochondral tissue specimens from five patients undergoing knee arthroplasty. These two areas underlaid the macroscopically and histologically best and worst cartilage, representing early and late-stage OA, respectively. BM-MSCs were co-cultured with normal chondrocytes suspended in agarose, with the two cell types separated by a porous membrane. After 0, 7, 14 and 21 days, chondrocyte-agarose scaffolds were assessed by gene expression and biochemical analyses, and the abundance of selected proteins in conditioned media was assessed by ELISA. Co-culture with late-OA BM-MSCs resulted in a reduction in GAG deposition and a decreased expression of genes encoding matrix-specific proteins (COL2A1 and ACAN), compared to culturing with early OA BM-MSCs. The concentration of TGF-ß1 was significantly higher in the early OA conditioned media. The results of this study have clinical implications for cartilage repair, suggesting that the health of the subchondral bone may influence the outcomes of chondrocyte-based repair strategies.

Does statin-treated hyperlipidemia affect rotator cuff healing or muscle fatty infiltration after rotator cuff repair?

BACKGROUND: Hyperlipidemia is linked to poor tendon-to-bone healing and progression of fatty infiltration after rotator cuff repair. Statins effectively treat hyperlipidemia, but it is unknown if they have any potential detrimental effects following rotator cuff repair. The aim of this study was to evaluate the effect of statins on rotator cuff healing and fatty infiltration following repair. METHODS: A total of 77 patients undergoing arthroscopic rotator cuff repair were recruited prospectively, 38 patients who were prescribed a statin for hyperlipidemia (statin group) and 39 patients who were not taking a statin (control group). Patients who did not have both preoperative and 1-year postoperative magnetic resonance imaging (MRI) scans were excluded from the study. Patient-reported outcome measures, namely the Western Ontario Rotator Cuff (WORC) index, Constant-Murley score, American Shoulder and Elbow Surgeons (ASES) score, and Disabilities of the Arm, Shoulder and Hand (DASH) score, were collected preoperatively and at 1 year. Fatty infiltration was assessed on MRI according to the Goutallier grade preoperatively and at 12 months; rotator cuff healing was assessed at 12 months according to the Sugaya classification. Following propensity score weighting to adjust for baseline imbalances, 12-month outcomes were compared between the 2 groups. RESULTS: At 12 months, all patient-reported outcome measures had improved significantly compared with baseline (WORC score, 85.9 vs. 32.5, P < .001; ASES score, 87.3 vs. 37.5, P < .001; Constant-Murley score, 77 vs. 31, P < .001; and DASH score, 13.6 vs. 61.4, P < .001). There was no significant difference in postoperative scores in the statin group vs. the control group (WORC score, 84.9 vs. 89.6, P = .94; ASES score, 87.5 vs. 86.6, P = .40; Constant-Murley score, 77 vs. 81, P = .90; and DASH score, 14.4 vs. 11.4, P = .14), and for 3 of these scores, the 95% confidence intervals excluded a clinically meaningful difference. Similarly, rotator cuff healing at 12 months and Goutallier fatty infiltration grades were comparable between the 2 groups. Retears were seen in 6 patients (15.8%) in the statin group and 8 (20.5%) in the control group. Progression of fatty infiltration was seen in 4 patients (10.5%) in the statin and 4 (10.3%) in the control group. Statin use did not demonstrate a significant association with either retear risk (P = .41) or progression of fatty atrophy (P = .69). CONCLUSION: Patient-reported outcomes, rotator cuff retear rate, and fatty infiltration on MRI at 12 months after rotator cuff repair in patients with hyperlipidemia treated with statins are similar to those in a control group.

Design and psychometric testing of a new patient-reported outcome measure for ankle treatment.

BACKGROUND: Several outcome scores are used to assess the outcome of ankle surgery, but many are not validated and there is currently no 'gold-standard'. Consequently, there is demand to develop a new 'gold-standard' score to assess ankle surgery. The study aim was to review existing scores to develop and validate a new patient-reported outcome measure (PROM) to assess the outcome of operative ankle surgery. METHODS: The questionnaire items covered three areas: pain, symptoms and activity. The scale was reviewed by a patient group, resulting in the Oswestry Ankle score (Os-Ankle). The Os-Ankle was validated using a cohort of 206 patients at both pre-operative and post-operative stages of ankle surgery. Patients provided two other outcome scores, the scores currently used at our centre: the Manchester-Oxford Foot Questionnaire (MOxFQ) and the Veterans Rand-12 (VR-12). Factor analysis and Rasch were determined to assess the psychometric testing and design of the Os-Ankle score. A follow up paper assesses the validity of the Os-Ankle against two existing scores. RESULTS: Results of the factor and Rasch analysis suggested that 12-items should be removed. The remaining 18-items fitted the Rasch model well, suggesting good internal consistency. CONCLUSION: A new ankle PROM, the Os-Ankle, was successfully developed and demonstrated good psychometric testing. The Os-Ankle evaluates pain, symptoms and activities and results in a single score. The Os-Ankle has been validated in our follow up paper, and is ready to be implemented by ankle clinicians to monitor clinical outcomes. With the publication of two back to back papers, it will allow for further engage with other clinicians and other centres. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Evaluating patient perspectives on participating in scientific research and clinical trials for the treatment of spinal cord injury.

A questionnaire was developed to evaluate patients' perspective on research aimed at improving functions and overcoming complications associated with spinal cord injury (SCI). The first three sections were based on published and validated assessment tools. The final section was developed to assess participant perspectives on research for SCI. One thousand patients were approached, of which 159 participated. Fifty-eight percent of participants were satisfied with their 'life as a whole'. Two factors could be generated that reflected the variance in the data regarding participants' life with a SCI: "Psychosocial and physical wellbeing" and "Independent living". The majority of participants stated they would be involved in research (86%) or clinical trials (77%). However, the likelihood of participation dropped when potential risks of the research/trials were explained. Which participants would be willing to participate in research could not be predicted based on the severity of their injury, their psychosocial and physical wellbeing or their independent living. Despite participant establishment of a life with SCI, our data indicates that individuals strive for improvements in function. Participant willingness to be included in research studies is noteworthy and scientists and clinicians are encouraged to involve more patients in all aspects of their research.

Perlecan in the Natural and Cell Therapy Repair of Human Adult Articular Cartilage: Can Modifications in This Proteoglycan Be a Novel Therapeutic Approach?

Articular cartilage is considered to have limited regenerative capacity, which has led to the search for therapies to limit or halt the progression of its destruction. Perlecan, a multifunctional heparan sulphate (HS) proteoglycan, promotes embryonic cartilage development and stabilises the mature tissue. We investigated the immunolocalisation of perlecan and collagen between donor-matched biopsies of human articular cartilage defects (n = 10 × 2) that were repaired either naturally or using autologous cell therapy, and with age-matched normal cartilage. We explored how the removal of HS from perlecan affects human chondrocytes in vitro. Immunohistochemistry showed both a pericellular and diffuse matrix staining pattern for perlecan in both natural and cell therapy repaired cartilage, which related to whether the morphology of the newly formed tissue was hyaline cartilage or fibrocartilage. Immunostaining for perlecan was significantly greater in both these repair tissues compared to normal age-matched controls. The immunolocalisation of collagens type III and VI was also dependent on tissue morphology. Heparanase treatment of chondrocytes in vitro resulted in significantly increased proliferation, while the expression of key chondrogenic surface and genetic markers was unaffected. Perlecan was more prominent in chondrocyte clusters than in individual cells after heparanase treatment. Heparanase treatment could be a means of increasing chondrocyte responsiveness to cartilage injury and perhaps to improve repair of defects.

Mechano-driven regeneration predicts response variations in large animal model based on scaffold implantation site and individual mechano-sensitivity.

It is well founded that the mechanical environment may regulate bone regeneration in orthopedic applications. The purpose of this study is to investigate the mechanical contributions of the scaffold and the host to bone regeneration, in terms of subject specificity, implantation site and sensitivity to the mechanical environment. Using a computational approach to model mechano-driven regeneration, bone ingrowth in porous titanium scaffolds was simulated in the distal femur and proximal tibia of three goats and compared to experimental results. The results showed that bone ingrowth shifted from a homogeneous distribution pattern, when scaffolds were in contact with trabecular bone (max local ingrowth 12.47%), to a localized bone ingrowth when scaffolds were implanted in a diaphyseal location (max local ingrowth 20.64%). The bone formation dynamics revealed an apposition rate of 0.37±0.28%/day in the first three weeks after implantation, followed by limited increase in bone ingrowth until the end of the experiment (12 weeks). According to in vivo data, we identified one animal whose sensitivity to mechanical stimulation was higher than the other two. Moreover, we found that the stimulus initiating bone formation was consistently higher in the femur than in the tibia for all the individuals. Overall, the dependence of the osteogenic response on the host biomechanics means that, from a mechanical perspective, the regenerative potential depends on both the scaffold and the host environment. Therefore, this work provides insights on how the mechanical conditions of both the recipient and the scaffold contribute to meet patient and location-specific characteristics.

Characterization of regional meniscal cell and chondrocyte phenotypes and chondrogenic differentiation with histological analysis in osteoarthritic donor-matched tissues.

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA). However, there is currently a lack of quantitative and objective metrics to assess OA meniscal cell phenotypes. In this study we investigated the phenotypic markers and chondrogenic potency of avascular and vascular meniscal cells and chondrocytes from medial OA knee joints (n = 10). Flow cytometry results showed that a significantly greater percentage of meniscal cells were positive for CD49b, CD49c and CD166 compared to donor-matched chondrocytes after 14 days in monolayer culture. The integrins, CD49b and CD29, were expressed at a significantly higher level on avascular meniscal cells derived from tissues with a more degenerated inner border than non-degenerate menisci, suggesting that the integrin family may play an important role in meniscus OA pathology. Collagen fibres arranged in a "tree-like" formation within the meniscus appeared to have less blood vessels associated with them in the vascular region of the most degenerate menisci, which may indicate that such structures are involved in the pathological process. We have demonstrated that meniscal cells derived from the lateral meniscus in medial OA patients have chondrogenic capacity in vitro and hence could represent a potential cell source to consider for meniscus tissue engineering.