Elevated Blood Tantalum Concentrations in Patients Following Reconstruction of Severe Acetabular Defects in Total Hip Arthroplasty Using Modular Tantalum Augments in Combination With Uncemented Tantalum Cups.

INTRODUCTION: The reconstruction of acetabular defects in total hip arthroplasty (THA) can be challenging. An option to treat uncontained acetabular defects is to use modular tantalum augments in combination with cementless press-fit cups. However, modularity is associated with an increased risk of debonding and mechanical failure. In addition, metal wear particles can be released due to micromotions at the implant interface. Clinical data on the long-term results of this treatment strategy is limited. The purposes of this study were: (1) to evaluate the clinical and radiological outcome of complex THA using modular trabecular metal augments and uncemented revision cups; (2) to investigate the blood tantalum concentrations in these patients at mid-term (mean 4.5 year) follow-up; and (3) to report complications and mechanisms of failure related to this procedure. MATERIALS AND METHODS: In this single-center study, we retrospectively reviewed data from a consecutive cohort of 27 patients who underwent complex acetabular defect reconstruction using a modular tantalum acetabular augment in combination with an uncemented tantalum cup. We evaluated the implant survival, and the radiological and clinical outcomes after a mean follow-up of 4.5 years (SD 2.1; range 2.5 to 10.6 years) using patient-reported outcome scores (PROMs). Blood samples were analyzed regarding tantalum concentration and compared with a control group. RESULTS: The cumulative survival rate at 4.5 years with the endpoint "revision of the acetabular component for aseptic loosening" was 94.4% (95% confidence interval (CI) 71.6 to 99.2) and 82.9% (95 % CI 60.5 to 93.3) for the endpoint "revision for any reason." The PROMs improved significantly up to the latest follow-up, and radiographic data showed no signs of loosening or implant migration. Median blood tantalum concentrations were significantly higher in the study group (0.15 µg/L) compared to the control group (0.002 µg/L) (P < 0.001). CONCLUSIONS: This study demonstrated acceptable clinical and radiological results of cementless revision THA using modular trabecular metal implants for the reconstruction of large acetabular defects. Tantalum concentrations were significantly higher in patients who had tantalum implants compared to the control group, however, the systemic and local effects of an increased tantalum exposure are not yet fully understood and have to be further investigated.

Neutral to slightly undercorrected mechanical leg alignment provides superior long-term results in patients undergoing matrix-associated autologous chondrocyte implantation.

PURPOSE: The aim of this study was to evaluate the role of leg alignment on long-term clinical outcome after matrix-associated autologous chondrocyte implantation (M-ACI) and to define an individualized target range to optimize clinical outcome. METHODS: The present study examined patients who underwent M-ACI of the femoral condyle. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) were used to assess the results. Clinical outcomes were related to Patient Acceptable Symptomatic State (PASS). For intra- and interobserver reliability of mechanical tibiofemoral angle, mechanical medial proximal tibial angle and mechanical lateral distal femoral angle, we calculated intraclass correlation coefficients using a two-way mixed model with absolute agreement. A regression model and receiver-operating characteristics curve were used to identify an individual range of alignment where a favourable clinical outcome could be expected in the long term. RESULTS: Additional osteotomy was performed in 50% of patients with similar clinical outcomes as physiologically aligned patients (p > 0.05). The curve-fitting regression model identified a target range of -2.5° valgus to 4.5° varus for ideal postoperative alignment (R2 = 0.12, p = 0.01). Patients within this range were more likely to achieve PASS (70% vs. 27%, p = 0.001). In medially treated defects, a refined range of -2.5° valgus to 4° varus alignment was found (R2 = 0.15, p = 0.01). These patients were more likely to achieve PASS (67% vs. 30%, p = 0.01) and showed favourable postoperative KOOS and MOCART scores (p = 0.02). Patients with lateral defects were more likely to achieve PASS within a range of -2° valgus and 0.5° varus (90% vs. 45%, p = 0.03) and showed favourable postoperative KOOS and MOCART scores (p = not significant). CONCLUSIONS: An individual range of leg alignment-whether achieved by osteotomy or physiologic alignment-should be respected in M-ACI treatment. A neutral to slightly undercorrected alignment favours the postoperative outcome after M-ACI. When planning surgery for patients with focal cartilage defects of the femoral condyle, these ranges should be recognized as critical factors. LEVEL OF EVIDENCE: Level III.

Femoral revision in total hip arthroplasty using a cementless modular stem: clinical and radiological results with a 8-year follow-up.

INTRODUCTION: Modular femoral components allow for patient-specific restoration of hip joint geometry and the reconstruction of extensive bone defects in revision total hip arthroplasty (THA); however, potential problems of modular implants such as taper corrosion and the risk of implant fracture continue to be of concern. The aim of the present study was to evaluate the clinical and radiological results of a cementless modular revision stem following revision surgery due to aseptic loosening and periprosthetic fracture and to assess patient-reported outcome measures (PROMs) in these patients at mid-term follow-up. MATERIALS AND METHODS: In this study, a consecutive cohort of 75 patients who underwent primary revision THA at our institution using a modular cementless stem design (MRP-TITAN stem) was retrospectively evaluated at a mean follow-up of 7.7 years. Kaplan-Meier survivorship analyses were performed with revision of the femoral component for any reason as the end point. The Harris-Hip Score, the UCLA Activity Score, the Forgotten Joint Score and the SF-12 Score were used for clinical assessment. We used the Wilcoxon signed rank test to compare pre- and postoperative clinical scores. RESULTS: Overall stem survival with the endpoint stem re-revision for any reason was 85.4% at a mean follow-up of 7.7 years (range 2.4-14 years). Stem survival was 89.5% in the aseptic loosening group and 78.3% in the periprosthetic fracture group with no statistically significant difference between both groups (p = 0.107). One patient had to be revised due to taper fracture. PROMs improved significantly up to the latest follow-up, and radiographic evaluation showed full osseointegration of all stems in this cohort. CONCLUSIONS: Revision THA using a modular cementless titanium revision stem demonstrated adequate clinical and radiological results at mid- to long-term follow-up in this cohort. Cementless revision stems are a useful treatment option to restore the anatomy, especially in deformed hips and in complex revision hip arthroplasty. However, there are some significant disadvantages related to an increased risk of mechanical failure such as corrosion/fretting damage and implant fracture. Future high-quality prospective studies with longer follow-up are necessary to confirm the supposed advantages.

Impact of Comorbidities and Previous Surgery on Mid-Term Results of Revision Total Knee Arthroplasty for Periprosthetic Joint Infection.

(1) Background: In the treatment of periprosthetic joint infection (PJI), the individual host status and previous surgical procedures appear to have a relevant influence on success rates and clinical outcome of knee revision surgery. Current data about the predictive value are limited in this subgroup of patients. (2) Methods: Retrospectively, 107 patients (109 knees) undergoing two-stage exchange knee arthroplasty for PJI using a rotating-hinge design with at least two years follow-up. The cumulative incidence (CI) for different endpoints was estimated with death as competing risk. Univariate and multivariate analyses for potential predictive factors were performed. Patient-related outcome measures (PROMs) for clinical outcome were evaluated. (3) Results: At 8 years, the CI of any revision was 29.6%, and of any reoperation was 38.9%. Significant predictors for risk of re-revision were the Charlson Comorbidity Index (CCI) and the number of previous surgical procedures prior to explanation of the infected implant. The functional and clinical outcome demonstrated acceptable results in the present cohort with a high comorbidity level. (4) Conclusions: A compromised host status and multiple previous surgical procedures were identified as negative predictors for re-revision knee surgery in the treatment of PJI. Reinfection remained the major reason for re-revision. Overall mortality was high.

Fixed-bearing is superior to mobile-bearing in lateral unicompartmental knee replacement: a retrospective matched-pairs analysis.

PURPOSE: Due to low incidence of isolated lateral osteoarthritis (OA), there are limited data on whether a fixed-bearing (FB) or a mobile-bearing (MB) design is superior for lateral unicompartmental knee replacement (UKR). The aim of this matched-pairs analysis was to compare both designs in terms of implant survival and clinical outcome. METHODS: Patients who received MB-UKR (Group A) and FB-UKR (Group B) at a single centre were matched according to gender, age at time of surgery and body mass index (BMI). Survivorship analysis was performed with the endpoint set as "revision for any reason". Clinical outcome was assessed using the Oxford knee score (OKS), visual analogue scale for pain (VAS), patients' satisfaction, University of California Los Angeles activity scale (UCLA) and the Tegner activity score (TAS). RESULTS: A total of 60 matched pairs were included with a mean follow-up (FU) of 3.4 ± 1.3 (range 1.2-5.0) years in Group A and 2.7 ± 1.2 (range 1.0-5.0) years in Group B. Survivorship between both groups differed significantly (Group A: 78.7%; Group B: 98.3%, p = 0.003) with bearing dislocation being the most common reason for revision in Group A (46.2%). The relative and absolute risk reduction were 92.2% and 20%, respectively, with 5 being the number needed to treat. There were no differences in OKS (Group A: 41.6 ± 6.5; Group B: 40.4 ± 7.7), VAS (Group A: 2.9 ± 3.2; Group B: 1.6 ± 2.2), UCLA (Group A: 5.7 ± 1.3; Group B: 5.9 ± 1.8) and TAS (Group A: 3.0 ± 1.0; Group B: 3.1 ± 1.2) between both groups on follow-up. CONCLUSION: Despite modern prosthesis design and surgical technique, implant survival of lateral MB-UKR is lower than that of FB-UKR on the short- to mid-term due to bearing dislocation as the most common cause of failure. Since clinical results are equivalent in both groups, FB-UKR should be preferred in treatment of isolated lateral OA. LEVEL OF EVIDENCE: Retrospective case-control study, Level III.

Short- to mid-term results of minimally invasive lateral unicompartmental knee replacement: 133 cases in a non-designer series.

INTRODUCTION: The aim of the current study was to demonstrate short- to mid-term survivorship as well as clinical outcome of lateral unicompartmental knee replacement (UKR) with a fixed-bearing (FB) design from a non-designer center using the Oxford Fixed Lateral prosthesis. MATERIALS AND METHODS: This single-center retrospective cohort study reports the results of 133 consecutive lateral FB-UKR. Survivorship analysis was performed with different endpoints and clinical outcome was measured using the Oxford-Knee-Score (OKS), American-Knee-Society-Score (AKSS-O), range-of-motion (ROM) and visual-analog-scale for pain (VAS). RESULTS: There were two revision surgeries with conversion to total knee replacements (TKR) due to persistent pain resulting in a survival rate of 98.5% (95% CI 93.5-99.6) with a mean follow-up (FU) of 3.3 ± 1.8 years (range 1-8.5). All outcome scores, VAS and ROM showed a significant improvement at final FU (p < 0.001). The OKS improved from 26 ± 7.8 (range 11-45) preoperatively to 39 ± 8.3 (range 13-48), the AKSS-O from 49.2 ± 14.6 (range 18-90) to 81.8 ± 15.1 (range 40-100), the AKSS-F from 53 ± 23.7 (range 0-100) to 80.4 ± 21.4 (range 5-100) and the ROM from 118 ± 17 (range 90-160) to 134 ± 9.5 (range 100-155). CONCLUSIONS: The short- to mid-term results following lateral FB-UKR demonstrate a high survivorship and good clinical outcome from an independent series. We, therefore, suggest that FB-UKR is a safe treatment option for isolated lateral OA if sufficient surgical experience is provided. LEVEL OF EVIDENCE: Retrospective cohort study, level IV.

Clinical and Functional Results of Cementless Unicompartmental Knee Arthroplasty with a Minimum Follow Up of 5 Years-A Consecutive Cohort of 201 Patients.

The number of unicompartmental knee replacements (UKR) is increasing. Alongside various advantages, the revision rate of cemented UKR is higher compared to total knee arthroplasty (TKR). In contrast, cementless fixation shows reduced revision rates, compared to the cemented UKR. However, most of the recent literature is based on designer-dependent studies. In this retrospective, single-center cohort study, we investigated patients who underwent cementless Oxford UKR (OUKR) between 2012 and 2016 in our hospital with a minimum follow-up of five years. Clinical outcome was evaluated using the OKS, AKSS-O, AKSS-F, FFbH-OA, UCLA, SF-36, EQ-5D-3L, FJS, ROM, pain, and satisfaction measures. Survival analysis was performed with reoperation and revision as endpoints. We included 201 patients (216 knees) for clinical evaluation. All outcome parameters increased significantly from pre- to postoperative stages. The five-year survival rate was 96.1% for revision surgery and 94.9% for reoperation. The main reasons for revision were the progression of osteoarthritis, inlay dislocation, and tibial overstuffing. Two iatrogenic tibial fractures appeared. Cementless OUKR shows excellent clinical outcome and high survival rates after five years. The tibial plateau fracture in cementless UKR represents a serious complication and requires modification of the surgical technique.

Physical Activity of Young Patients following Minimally Invasive Lateral Unicompartmental Knee Replacement.

Unicompartmental knee replacement (UKR) has increased in popularity in recent years, especially in young patients with high demands on their athletic ability. To date, there are no data available on the physical activity of young patients following lateral UKR. The aim of this study was to demonstrate return-to-activity rate and sporting activity of patients aged 60 years or younger following lateral UKR with a fixed-bearing (FB) prosthesis. Thirty-seven patients aged 60 years or younger after lateral FB-UKR were included. Sporting activities were assessed using the University of California Los Angeles activity scale (UCLA) and the Tegner activity score (TAS). Clinical outcome was measured using the Oxford Knee Score (OKS), range of motion (ROM) and visual analogue scale (VAS). The mean follow-up (FU) was 3.1 ± 1.5 years and the mean age at surgery was 52.8 ± 3.1 years. The return-to-activity rate was 87.5% and 49% of patients were highly active postoperatively as defined by an UCLA score of 7 or higher. All clinical parameters increased significantly postoperatively. We demonstrated a high return-to-activity rate with nearly half of the patients achieving high activity levels. Longer FU periods are necessary to evaluate the effect of activity on implant survival.

Minimally invasive Oxford medial unicompartmental knee replacement in patients 50 years of age or younger.

INTRODUCTION: The aim of the present study was to assess clinical outcome and mid-term survivorship of mobile-bearing unicompartmental knee arthroplasty in patients 50 years of age or younger. METHODS: This study reports the results of 119 patients (130 knees) following mobile-bearing medial UKA. Primary indication was advanced osteoarthritis or avascular necrosis of the femoral condyle. The anterior cruciate ligament (ACL) as well as the collateral ligaments were functionally intact, the varus deformity was manually correctable and there was no evidence of osteoarthritis in the lateral compartment. Survivorship analysis was performed with different endpoints and clinical outcome was measured using the Oxford Knee Score (OKS), American Knee Society Score and Functional Score (AKSS-O, AKSS-F), range of motion (ROM), Tegner activity score, University of California Los Angeles score (UCLA) and visual analogue scale for pain (VAS). RESULTS: The survival rate was 96.6% at 6.5 years (95% CI 98.7-91.3%; number at risk: 56) and 91.7% (95% CI 96.7-80%; number at risk: 22) at 10 years for the endpoint device related revisions and 91.5% at 6.5 years (95% CI 95.4-84.5%; number at risk: 56) and 86.8% (95% CI 93-76.2%; number at risk: 22) at 10 years for the endpoint revision for any reason. Outcome scores, VAS and ROM showed significant improvements (p < 0.001). The mean OKS increased from 26.7 (standard deviation (sd): 7.2) preoperatively to 40.9 (sd: 7.6) at final follow-up, the mean AKSS-O from 48.3 (sd: 13.3) to 87.8 (sd: 14.4) and the mean ROM from 118° (sd: 16.7) to 125° (sd: 11.4). The radiological analysis revealed progression of degenerative changes in the lateral compartment in 39.6% of patients without affecting the functional outcome. CONCLUSIONS: Medial mobile-bearing UKA is a viable surgical treatment option in young patients with significant improvements in knee function and pain. Further follow-up is necessary to evaluate the long-term efficacy. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Mobile bearing versus fixed bearing medial unicompartmental knee replacement: an independent two center matched-pairs analysis.

INTRODUCTION: The aim of the present study was to compare clinical outcome between patients following fixed-bearing (FB) or mobile-bearing (MB) unicompartmental knee replacement (UKR) for antero-medial knee osteoarthrosis (OA) at two independent orthopedic centers. MATERIALS AND METHODS: Matched-pairs were built between 35 patients receiving FB-UKR and 52 patients following MB-UKR regarding age at time of surgery, body mass index (BMI) and range of motion (ROM) preoperatively. Clinical and functional outcome was measured postoperatively by the American Knee Society Score (AKSS-O/AKSS-F), ROM, Tegner Activity Scale (TAS) as well as the Short Form 36 Health Survey (SF-36). RESULTS: The average treatment effect of the treated (ATT) after propensity score matching showed a significantly superior ROM in patients following MB-UKR (FB: 118°, MB: 124°). All remaining parameters had no statistically significant differences between both groups involving TAS, AKSS and SF-36. CONCLUSIONS: The present study suggests that MB-UKR can provide a greater ROM compared to FB-UKR on comparable patients. The authors believe that both designs are suitable for adequate improvement of clinical outcome and ROM for patients suffering from antero-medial osteoarthrosis of the knee joint. LEVEL OF EVIDENCE: Retrospective cohort study, Level IV.

Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability.

Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4+CD25+/high CD127low/-) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions-especially in the SM-are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms.

Fast Return to Sports and High Level of Activity after Cementless Oxford Unicompartmental Knee Arthroplasty.

Physical activity is essential for overall health. For patients undergoing knee arthroplasty, questions about the implant's suitability for sports arise. The general recommendations for physical activity with knee replacements are often based upon experts' opinions, with a lack of scientific data. This study was performed at an independent high-volume center and aimed to investigate what level of activity patients can achieve and how they perform with a well-functioning cementless unicompartmental knee replacement (UKR). Possible differences in outcome in regards to patients' body mass index (BMI) were also examined. A total of 228 knees treated with cementless Oxford UKR (OUKR) were followed up after a mean of 37.1 months. Tegner's and UCLA (University of California, Los Angeles) scores were obtained to assess the level of physical activity. The Schulthess Clinical Activity Questionnaire was assessed for detailed information on practiced sports, and the SF-36 questionnaire was evaluated to analyze patients' quality of life. The return to activity rate was 92.9%. In total, 64% of the physically active patients had already taken up sports within 3 months after surgery. Mean Tegner's score was at 3.5, and mean UCLA score was at 6.3. High impact sports were not performed very often after surgery. Higher BMI showed a negative correlation with the numbers of sports (rsp = -0.289) as well as Tegner's (rsp = -0.222) and UCLA (rsp = -0.383) scores. The SF-36 scores were comparably good to those in an age-equivalent standard reference group. In conclusion, cementless OUKR allows a fast return to activity with a high level of physical exercise. Patients with increased BMI tend to practice less types of sports with decreased activity scores.

Pulsatile Lavage Systems with High Impact Pressure and High Flow Produce Cleaner Cancellous Bone Prior to Cementation in Cemented Arthroplasty.

In cemented joint arthroplasty, state-of-the-art cementing techniques include high-pressure pulsatile saline lavage prior to cementation. Even with its outstanding importance in cementation, there are surprisingly few studies regarding the physical parameters that define pulsatile lavage systems. To investigate the parameters of impact pressure, flow rate, frequency and the cleaning effect in cancellous bone, we established a standardized laboratory model. Standardized fat-filled carbon foam specimens representing human cancellous bone were cleaned with three different high-pressure pulsatile lavage systems. Via CT scans before and after cleaning, the cleaning effect was evaluated. All systems showed a cleaning depth of at least 3.0 mm and therefore can be generally recommended to clean cancellous bone in cemented joint arthroplasty. When comparing the three lavage systems, the study showed significant differences regarding cleaning depths and volume, with one system being superior to its peer systems. Regarding the physical parameters, high impact pressure in combination with high flow rate and longer distance to the flushed object seems to be the best combination to improve the cleaning of cancellous bone and therefore increase the chances of a deeper cement penetration that is required in cemented joint arthroplasty. In summary, this study provides the first standardized comparison of different lavage systems and thus gives initial guidance on how to optimally prepare cancellous bone for cemented joint arthroplasty.

Bearing Thickness Is Not a Predictive Factor for Damage and Penetration in Oxford Unicompartmental Knee Arthroplasty-A Retrieval Analysis.

The medial Oxford unicompartmental knee arthroplasty (OUKA) shows good survivorship, as well as clinical results. Aseptic loosening, however, remains one of the main reasons for revision and polyethylene debris is known to cause aseptic loosening. The role of bearing thickness in total as well as unicondylar knee arthroplasty has been the subject of controversial discussions, especially the longevity of lower thickness bearings in total knee arthroplasty was questioned. The purpose of this study was to assess the influence of bearing thickness on time to revision, damage pattern, penetration, and volumetric material loss. A cohort of 47 consecutively retrieved medial OUKA bearings was analyzed with conventional direct light microscopy applying the Hood damage analysis, as well as measuring the penetration depth. In this retrieval cohort, a difference on survival time, damage, penetration, as well as volumetric material loss could not be seen. We conclude that low as well as high thickness bearings can safely be used in OUKA without any relevant differences in terms of wear and damage.

T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability.

Despite the growing body of literature demonstrating a crucial role of T helper cell (Th) responses in the pathogenesis of osteoarthritis (OA), only few clinical studies have assessed interactions between Th cells and OA-related symptoms. Yet, the inclusion of clinical data in the interpretation of cellular analyses of Th cell infiltration is essential to reveal the mechanisms underlying the complex pathophysiology of OA pain and disability. Thus, the aim of the study was to analyze the infiltration pattern of Th cells in systemic (peripheral blood) and joint-derived (synovial membrane and fluid) samples from patients with knee OA in relation to OA-induced pain and disability. Therefore, radiographic OA severity, knee pain and function of 47 OA patients undergoing knee arthroplasty were evaluated prior to surgery. In parallel, samples of peripheral blood (PB), synovial membrane (SM) and synovial fluid (SF) were harvested and analyzed for different Th subsets using flow cytometry. According to surface marker expression Th cells (CD3+ CD4+ CD8-) were assigned to the Th subsets Th1 (CXCR3+, CCR5+), Th2 (CCR3+, CCR4+) and Th17 (CD161+, CCR6+). Interestingly, infiltration of the SM with all Th subtypes (Th1, Th2, Th17) significantly correlated with OA-induced disability. Most importantly, synovial CCR5+ and CCR3+ Th cell infiltration was associated with OA-related knee pain and disability. Furthermore, higher percentage rates of CXCR3+ Th cells in all tissue samples (PB, SM, SF) showed significant associations with OA severity. In contrast, increasing percentage rates of CD161+ Th cells in SM samples corresponded to a better functional outcome. In conclusion, the current study provides an extensive profile of the Th cell infiltration pattern in PB, SF and SM from patients with clinically relevant knee OA. Th cell infiltration of the SM might play a crucial role not only in the pathogenesis of OA but also in the development of OA-related knee pain and disability.

Prospective Long-term Follow-up of Autologous Chondrocyte Implantation With Periosteum Versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial.

BACKGROUND: Matrix-associated autologous chondrocyte implantation (MACI) is a further development of the original autologous chondrocyte implantation periosteal flap technique (ACI-P) for the treatment of articular cartilage defects. PURPOSE: We aimed to establish whether MACI or ACI-P provides superior long-term outcomes in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 21 patients with cartilage defects at the femoral condyle were randomized to MACI (n = 11) or ACI-P (n = 10) between the years 2004 and 2006. Patients were assessed for subjective International Knee Documentation Committee (IKDC) score, Lysholm and Gillquist score, Tegner Activity Score, and 36-Item Short Form Health Survey (SF-36) preoperatively (T0), at 1 and 2 years postoperatively (T1, T2), and at the final follow-up 8 to 11 years after surgery (T3). Onset of osteoarthritis was determined using the Kellgren-Lawrence score and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and delayed gadolinium-enhanced MRI of cartilage was used to evaluate the cartilage. Adverse events were recorded to assess safety. RESULTS: There were 16 patients (MACI, n = 9; ACI-P, n = 7) who were reassessed on average 9.6 years after surgery (76% follow-up rate). The Lysholm and Gillquist score improved in both groups after surgery and remained elevated but reached statistical significance only in ACI-P at T1 and T2. IKDC scores increased significantly at all postoperative evaluation time points in ACI-P. In MACI, IKDC scores showed a significant increase at T1 and T3 when compared with T0. In the majority of the patients (10/16; MACI, 5/9; ACI-P, 5/7) a complete defect filling was present at the final follow-up as shown by the MOCART score, and 1 patient in the ACI-P group displayed hypertrophy of the repair tissue, which represents 6% of the whole study group and 14.3% of the ACI-P group. Besides higher SF-36 vitality scores in ACI-P at T3, no significant differences were seen in clinical scores and MRI scores between the 2 methods at any time point. Revision rate was 33.3% in MACI and 28.6% in ACI-P at the last follow-up. CONCLUSION: Our long-term results suggest that first- and third-generation ACI methods are equally effective treatments for isolated full-thickness cartilage defects of the knee. With the number of participants available, no significant difference was noted between MACI and ACI-P at any time point. Interpretation of our data has to be performed with caution due to the small sample size, which was further limited by a loss to follow-up of 24%.

Significance of MEF2C and RUNX3 Regulation for Endochondral Differentiation of Human Mesenchymal Progenitor Cells.

Guiding progenitor cell development between chondral versus endochondral pathways is still an unachieved task of cartilage neogenesis, and human mesenchymal progenitor cell (MPC) chondrogenesis is considered as a valuable model to better understand hypertrophic development of chondrocytes. Transcription factors Runx2, Runx3, and Mef2c play prominent roles for chondrocyte hypertrophy during mouse development, but little is known on the importance of these key fate-determining factors for endochondral development of human MPCs. The aim of this study was to unravel the regulation of RUNX2, RUNX3, and MEF2C during MPC chondrogenesis, the pathways driving their expression, and the downstream hypertrophic targets affected by their regulation. RUNX2, RUNX3, and MEF2C gene expression was differentially regulated during chondrogenesis of MPCs, but remained low and unregulated when non-hypertrophic articular chondrocytes were differentiated under the same conditions. RUNX3 and MEF2C mRNA and protein levels rose in parallel to hypertrophic marker upregulation, but surprisingly, RUNX2 gene expression changed only by trend and RUNX2 protein remained undetectable. While RUNX3 expression was driven by TGF-ß and BMP signaling, MEF2C responded to WNT-, BMP-, and Hedgehog-pathway inhibition. MEF2C but not RUNX3 levels correlated significantly with COL10A1, IHH, and IBSP gene expression when hypertrophy was attenuated. IBSP was a downstream target of RUNX3 and MEF2C but not RUNX2 in SAOS-2 cells, underlining the capacity of RUNX3 and MEF2C to stimulate osteogenic marker expression in human cells. Conclusively, RUNX3 and MEF2C appeared more important than RUNX2 for human endochondral MPC chondrogenesis. Pathways altering the speed of chondrogenesis (FGF, TGF-ß, BMP) affected RUNX2 or RUNX3, while pathways changing hypertrophy (WNT, PTHrP/HH) regulated mainly MEF2C. Taken together, reduction of MEF2C levels is a new goal to shift human cartilage neogenesis toward the chondral pathway.

What Is the Long-term (27- to 32-year) Survivorship of an Uncemented Tapered Titanium Femoral Component and Survival in Patients Younger Than 50 Years?

BACKGROUND: Uncemented femoral components in primary THA are in widespread use, especially in patients younger than 50 years, but few studies have evaluated their survival into the late third and early fourth decade. QUESTIONS/PURPOSES: We evaluated (1) survivorship using femoral revision for any reason as the endpoint, (2) survivorship using femoral revision for aseptic loosening as the endpoint, (3) survival in patients younger than 50 years, (4) cumulative incidence of stem revision for periprosthetic femoral fracture and (5) the overall risk of revision (change of any part of the implanted components) at a minimum of 27 years of follow-up with an uncemented tapered titanium stem still in clinical use today. METHODS: We reviewed the clinical and radiographic results of 326 THAs performed in 326 patients (for 28 patients with bilateral THA, only the first hip was included in the analysis to ensure independent observations) using an uncemented grit-blasted, tapered collarless titanium alloy (TiAl6Nb7) stem between January 1985 and December 1989. In that same timeframe, we performed 1038 primary THAs. During that time, we used cementless stems in patients without severe femoral canal deformity and adequate bone stock for uncemented femoral fixation as determined by using the indication criteria described by the developer. In all, 34% (354 of 1038) were cementless; all cementless stems implanted during that time were the stem being studied here. No others were used. The mean (range) age at the time of surgery was 56 years (13-81 years). Sixty-seven patients were younger than 50 years at the time of primary THA. A competing risk survivorship analysis was used to estimate long-term survival. The minimum follow-up was 27 years (mean 28 years; range 27-32 years); at that time, 169 patients had died, and four patients were lost to follow-up. RESULTS: Survivorship at 28 years with revision of the femoral component for any reason as the endpoint was 87% (95% CI 83 to 90). Survivorship for femoral revision for aseptic loosening as the endpoint was 94% at 28 years (95% CI 90 to 96). Survival in patients younger than 50 years at the time of primary THA was 89% (95% CI 78 to 95) and 95% (95% CI 86 to 98) at 28 years for the endpoints of all stem revisions and aseptic stem loosening, respectively. The overall cumulative incidence of stem revision for periprosthetic femoral fracture was 4% (95% CI 2 to 7) at 28 years. The overall THA survival rate at 28 years with revision for any reason as the endpoint was 57% (95% CI 51 to 62). CONCLUSIONS: Uncemented femoral fixation of a tapered collarless titanium alloy stem was reliable into the early fourth decade, especially in patients younger than 50 years. Late stem failures in the third and early fourth decade were mainly because of periprosthetic femoral fracture, while aseptic loosening occurred in undersized stems during the early second decade. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Minimally invasive lateral unicompartmental knee replacement: Early results from an independent center using the Oxford fixed lateral prosthesis.

PURPOSE: The aim of the present study was to assess clinical outcome as well as short-term survivorship of fixed-bearing lateral unicompartmental knee replacement (UKR) from a non-designer centre using the Oxford Fixed Lateral prosthesis. METHODS: This single-centre retrospective cohort study reports the short-term results of 51 consecutive patients (52 knees) after fixed-bearing lateral UKR with a minimum follow-up of one year. Survivorship analysis was performed with different endpoints and clinical outcome was measured using the Oxford Knee Score (OKS), objective American Knee Society Score (AKSS-O), range-of-motion (ROM), visual analog scale for pain (VAS), Tegner activity score and UCLA score. RESULTS: There was no revision surgery, defined as exchange of at least one of the components resulting in a survival rate of 100% at two years. Three patients required further surgical treatment resulting in a survival rate of 94.2% (95% confidence interval (CI): 83.2-98.1%) with the endpoint 'any reoperation'. Outcome scores, VAS and ROM showed a statistically significant improvement at final follow-up (P < .001). The OKS improved from 26.4 ±â€¯6.9 (12-41) preoperatively to 39.7 ±â€¯8.4 (15-48), the AKSS-O from 54.3 ±â€¯15.3 (18-90) to 82.2 ±â€¯15.6 (40-100), the American Knee Society Functional Score from 56.4 ±â€¯21.3 (10-100) to 83.1 ±â€¯20.2 (five to 100) and the ROM from 123.5 ±â€¯13.5 (90-140) to 134 ±â€¯10.3 (95-150). CONCLUSION: Early results of fixed-bearing lateral UKR using the Oxford-Fixed-Lateral prosthesis were encouraging with a significant improvement in pain and knee function as well as an excellent survivorship of 100% at a mean follow-up of two years. Further follow-up is necessary to evaluate the long-term effectiveness of this device and the surgical technique. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.

Synovial Cytokines Significantly Correlate with Osteoarthritis-Related Knee Pain and Disability: Inflammatory Mediators of Potential Clinical Relevance.

The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor ß; SCGF-ß) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-ß, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory (IL-7, IL-12, IFN-γ) cytokines, as well as growth factors (SCGF-ß, VEGF), correlated significantly with the level of knee pain. Poorer knee function was associated with higher IL-6, IL-10, IL-12, IL-13, IL-18, ßNGF, SCGF-ß, VEGF and CXCL9 levels. In conclusion, this study provides an extensive profile of synovial inflammatory mediators in knee OA and identifies cytokines of potential clinical relevance. In fact, five of the mediators examined (IL-10, IL-12, IL-13, SCGF-ß, VEGF) significantly correlate with both knee pain and function.