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.

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.

What Is the Correlation between Clinical and Radiographic Findings in Patients with Advanced Osteoarthritis of the Knee?

Knee range of motion and patient-reported outcome measures (PROMs) are often used as screening tools to assess the severity of knee osteoarthritis and guide the decision to refer patients to an arthroplasty clinic. However, there is little understanding regarding the correlation between these factors. Thus, the purpose of this study was to determine the correlation between patient-reported clinical function measured with the Oxford Knee Score (OKS), pain assessed using the visual analog scale (VAS), knee range of motion (ROM), and characteristic radiographic features in patients with advanced osteoarthritis of the knee. A prospective analysis of a consecutive series of 138 patients with advanced unilateral osteoarthritis (OA) of the knee was performed. The severity of radiographic OA was classified according to the most commonly used Kellgren and Lawrence classification (K&L). Spearman's rank correlation analysis and multiple linear regression analysis were performed. The OKS was used as a dependent variable and was adjusted for pain, ROM, and nine standardized radiographic parameters on multiple views of the tibiofemoral and patellofemoral joint. OKS and pain correlated weakly with the K&L grade (r = -0.289; p = 0.001; r = 0.258; p = 0.002). K&L grade and the degree of patellofemoral joint space narrowing were identified as independent factors being associated with a poorer OKS (coefficient -4.528, p = 0.021; coefficient -2.211, p = 0.038). Slightly worse results were identified for OKS and pain in patients with K&L grade 4 osteoarthritis compared to patients with K&L grade 3 osteoarthritis (∆OKS 5.5 points, p < 0.001; ∆VAS 1.7 points, p = 0.003). There was no significant difference for passive range of motion between patients with K&L grade 3 or 4. When counseling patients with advanced knee osteoarthritis who may be eligible for knee arthroplasty, it is essential to give primary consideration to pain levels and self-reported limitations experienced during daily activities. Relying solely on knee ROM and PROMs is not an effective screening method for guiding the decision to refer patients to an arthroplasty clinic.

Minimum 20-year follow-up of a press-fit acetabular cup in cementless total hip replacement in young patients.

PURPOSE: We aimed to determine the minimum 20-year survival rates of a cementless press-fit cup in young patients. PATIENTS AND METHODS: This is a retrospective, single-center, multi-surgeon cohort study investigating the minimum 20-year clinical and radiological outcome of the first 121 consecutive total hip replacements (THRs) using a cementless, press-fit cup (Allofit, Zimmer, Warsaw, IN, USA) performed between 1999 and 2001. 28-mm metal-on-metal (MoM) and ceramic-on-conventionally not highly crosslinked polyethylene (CoP) bearings were used in 71% and 28%, respectively. Median patient age at surgery was 52 (range 21-60) years. Kaplan-Meier survival analysis was conducted for different endpoints. RESULTS: The 22-year survival rate for the endpoint aseptic cup or inlay revision was 94% (95% confidence interval [CI] 87-96) and 99% (CI 94-100) for aseptic cup loosening. 20 patients (21 THRs; 17%) had died and 5 (5 THRs; 4%) were lost to follow-up. No THR showed evidence of radiographic cup loosening. Osteolysis was observed in 40% of THRs with MoM and 77% with CoP bearings. 88% of THRs with CoP bearings showed significant polyethylene wear. CONCLUSION: The investigated cementless press-fit cup, which is still in clinical use today, showed excellent long-term survival rates in patients under the age of 60 years at surgery. However, osteolysis due to polyethylene and metal wear was frequently observed and is a matter of concern in the third decade after surgery.

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.

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.

NFκB inhibition to lift the mechano-competence of mesenchymal stromal cell-derived neocartilage toward articular chondrocyte levels.

BACKGROUND: Fully functional regeneration of skeletal defects by multipotent progenitor cells requires that differentiating cells gain the specific mechano-competence needed in the target tissue. Using cartilage neogenesis as an example, we asked whether proper phenotypic differentiation of mesenchymal stromal cells (MSC) into chondrocytes in vitro will install the adequate biological mechano-competence of native articular chondrocytes (AC). METHODS: The mechano-competence of human MSC- and AC-derived neocartilage was compared during differentiation for up to 35 days. The neocartilage layer was subjected to physiologic dynamic loading in a custom-designed bioreactor and assayed for mechano-sensitive gene and pathway activation, extracellular matrix (ECM) synthesis by radiolabel incorporation, nitric oxide (NO) and prostaglandin E2 (PGE2) production. Input from different pathways was tested by application of agonists or antagonists. RESULTS: MSC and AC formed neocartilage of similar proteoglycan content with a hardness close to native tissue. Mechano-stimulation on day 21 and 35 induced a similar upregulation of mechano-response genes, ERK phosphorylation, NO production and PGE2 release in both groups, indicating an overall similar transduction of external mechanical signals. However, while AC maintained or enhanced proteoglycan synthesis after loading dependent on tissue maturity, ECM synthesis was always significantly disturbed by loading in MSC-derived neocartilage. This was accompanied by significantly higher COX2 and BMP2 background expression, > 100-fold higher PGE2 production and a weaker SOX9 stimulation in response to loading in MSC-derived neocartilage. Anabolic BMP-pathway activity was not rate limiting for ECM synthesis after loading in both groups. However, NFκB activation mimicked the negative loading effects and enhanced PGE2 production while inhibition of catabolic NFκB signaling rescued the load-induced negative effects on ECM synthesis in MSC-derived neocartilage. CONCLUSIONS: MSC-derived chondrocytes showed a higher vulnerability to be disturbed by loading despite proper differentiation and did not acquire an AC-like mechano-competence to cope with the mechanical stress of a physiologic loading protocol. Managing catabolic NFκB influences was one important adaptation to install a mechano-resistance closer to AC-derived neocartilage. This new knowledge asks for a more functional adaptation of MSC chondrogenesis, novel pharmacologic co-treatment strategies for MSC-based clinical cartilage repair strategies and may aid a more rational design of physical rehabilitation therapy after AC- versus MSC-based surgical cartilage intervention.

The primary stability of the femoral component in cemented single and twin peg Oxford unicompartmental knee arthroplasty under adverse conditions.

AIMS: The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation. METHODS: Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora. We generated 5° bone defects at the posterior condyle. Relative movement was simulated using a servohydraulic pulser, and analyzed at 70°/115° knee flexion. Relative movement was surveyed at seven points of measurement on implant and bone, using an optic system. RESULTS: At the main fixation zone, the twin peg shows less relative movement at 70°/115°. At the transition zone, relative movements are smaller for the single peg for both angles. The single peg shows higher compression at 70° flexion, whereas the twin peg design shows higher compression at 115°. X-displacement is significantly higher for the single peg at 115°. CONCLUSION: Bony defects should be avoided in OUKA. The twin peg shows high resilience against push-out force and should be preferred over the single peg. Cite this article: Bone Joint Res 2022;11(2):82-90.

Mid-term results of complex primary total knee arthroplasty using a rotating-hinge implant.

BACKGROUND: The indications and outcomes of semi- or fully-constrained knee implants in primary total knee arthroplasty (TKA) are still controversially discussed. The present study aims to evaluate the mid-term results and complications of a modular/non-modular rotating-hinge implant in complex primary TKA. METHODS: Eighty-two patients (86 knees) following primary TKA were retrospectively evaluated with a mean follow-up of 63 months. The functional outcome was assessed using the American Knee Society Score (AKSS) and the Oxford Knee Score (OKS). A Visual Analog Scale (VAS) was used to determine pain levels. Implant survival and reoperation rateswere estimated using competing risk analysis. Cox regression analysis wasperformed to evaluate the influence of modularity on implant survival. RESULTS: The survival rate with the endpoint implant revision was 90% (95 %CI:83-98%) and the survival rate with the endpoint all reoperations was 84% (95 %CI:75-94%) at 7 years. The AKSS improved significantly from 24 (SD 14.9, range:0-69) preoperatively to 83 (SD 14.3, range:57-100) postoperatively (p < 0.001); functional AKSS improved significantly from 27 (SD 24.3, range:0-100) to 46 (SD: 32.9, range 0-100) (p = 0.003), and OKS from 19 (SD: 8.3, range:5-43) to 29 (SD: 10.7, range:6-48), respectively (p < 0.0001). VAS decreased significantly from 8 (SD: 2.6, range:0-10) preoperatively to 3 (SD: 2.9, range:0-9) postoperatively (p < 0.0001). There was no significant influence of modularity on revision rates comparing modular to non-modular implants (p = 0.072). CONCLUSIONS: The present rotating-hinge implant provides substantial improvement in function and reduction of pain with good implant survival in the mid-term. Modularity was not associated with higher rates of revision.

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.

Peripheral Blood Lymphocyte Subpopulations in Patients Following Small Diameter Metal-On-Metal Total Hip Replacement at Long-Term Follow-Up.

(1) Background: The objective of the present study was to investigate peripheral blood lymphocyte subpopulations in patients with small diameter metal-on-metal total hip arthroplasty (MoM THA) and elevated blood metal ion concentrations at long-term follow-up. The hypothesis was that increased blood metal ion levels or the presence of adverse local tissue reactions (ALTR) would be associated with changes in the peripheral expression of lymphocyte subpopulations, which could potentially serve as early diagnostic markers for metal wear related complications. (2) Methods: Peripheral blood samples were analyzed for leucocyte subgroups (CD3+, CD4+, CD8+, CD14+, CD16+/CD56+, CD25+/CD127-, CD19+, IFN-γ+, IL-4+ and IL-17A+ cells) in 34 patients with elevated blood metal ion levels (combined cobalt and chromium levels >2 µg/L) following small head MoM THA at a mean follow-up of 15.6 years. Fifteen patients with small head MoM THA and blood metal ion levels within the normal range and 15 patients with conventional ceramic-on-polyethylene THA served as control groups. In addition, blood metal ion levels and leucocyte subpopulations were compared between patients with and without adverse local tissue reactions (ALTR), which was investigated by MRI in 27 patients of the study cohort. (3) Results: There was a significant decrease in the levels of IFN-γ+ Type-1 T helper cells (Th1) in patients with MoM THA compared to the ceramic-on-polyethylene control group (p < 0.001). No statistically significant differences in the cell counts of other lymphocyte subpopulations were found between the three groups. Cobalt ion levels were significantly higher in patients with ALTR (p < 0.001) compared to the non-ALTR group, but no differences in the levels of lymphocyte subsets were found between the two groups. (4) Conclusions: No adverse systemic effects with respect to peripheral blood leucocyte subpopulations could be detected in the present study in patients following THA with a small diameter MoM articulation at long-term follow-up. We found a significant decrease of IFN-γ+ Th1 cells in patients with MoM THA compared to the control group, but no differences in the peripheral expression of leucocyte subpopulations were seen between patients with and without ALTR. Future studies with larger patient cohorts and additional histopathological investigations could help to better understand the role of Th1 cells and other cell lines of the adaptive immune system in the development of metal wear related complications after total joint replacement.

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.

The Migration Pattern of a Cementless Hydroxyapatite-Coated Titanium Stem under Immediate Full Weight-Bearing-A Randomized Controlled Trial Using Model-Based RSA.

(1) Background: High primary stability is important for the long-term survival of cementless femoral stems in total hip arthroplasty (THA). The objective of this study was to investigate the migration pattern of a hydroxyapatite-coated cementless hip stem developed for minimally invasive surgery using model-based radiostereometric analysis (RSA). (2) Methods: In this randomized controlled trial, 44 patients with an indication for cementless primary THA were randomly allocated to receive either the SL-PLUS MIA stem, developed for minimally invasive surgery, or the SL-PLUS stem (Smith & Nephew Orthopaedics, Baar, Switzerland) which served as a control group. Unlimited weight-bearing was permitted postoperatively in both groups. Model-based RSA was performed after six weeks and after 3, 6, 12 and 24 months postoperatively. (3) Results: Mean total stem subsidence at two-year follow-up was 0.40 mm (SD 0.66 mm) in the SL-PLUS group and 1.08 mm (SD 0.93 mm) in the SL-PLUS MIA group (p = 0.030). Stem subsidence occurred during the first six weeks after surgery, indicating initial settling of the stem under full weight-bearing. Both stem designs showed good osseointegration and high secondary stability with no further migration after initial settling. (4) Conclusions: Settling of a cementless straight femoral stem occurs during the first six weeks after surgery under full weight-bearing. Although initial stem migration was higher in the SL-PLUS MIA group, it had no influence on secondary stability. All implants showed good osseointegration and high secondary stability with no signs of implant loosening during this two-year follow-up period.

Cementless Oxford Medial Unicompartmental Knee Replacement-Clinical and Radiological Results of 228 Knees with a Minimum 2-Year Follow-Up.

(1) Background: Studies show several advantages of unicompartmental knee replacement (UKR) over total knee replacements (TKR), whereas registry based revision rates of UKR are significantly higher than for TKA. Registry data report lower revision rates for cementless UKR compared to cemented UKR. The aim of this study was to assess clinical and radiological results of cementless Oxford UKR (OUKR) in an independent cohort. (2) Methods: This retrospective cohort study examines a consecutive series of 228 cementless OUKR. Clinical outcome was measured using functional scores (Oxford Knee Score (OKS), American Knee Society Score (AKSS), Hannover Functional Ability Questionnaire for Osteoarthritis (FFbH-OA), range of motion (ROM)), pain and satisfaction. Radiographs were analyzed regarding the incidence of radiolucent lines (RL), implant positioning, and their possible impact on clinical outcome. (3) Results: At a mean follow-up of 37.1 months, the two and three year revision free survival-rates were 97.5% and 96.9%. Reasons for revision surgery were progression of osteoarthritis, inlay dislocation and pain. All clinical outcome scores showed a significant improvement from pre- to postoperative. The incidence of RL around the implant was highest within the first year postoperatively (36%), and decreased (5%) within the second year. Their presence was not correlated with inferior clinical outcome. Implant positioning showed no influence on clinical outcome. (4) Conclusion: Cementless OUKR showed excellent clinical outcome and survival rates, with reliable osteointegration. Neither the incidence of radiolucent lines nor implant positioning were associated with inferior clinical outcome.

Impact of Mononuclear Cell Infiltration on Chondrodestructive MMP/ADAMTS Production in Osteoarthritic Knee Joints-An Ex Vivo Study.

Progressive loss of joint function in osteoarthritis (OA) is driven by degenerative and inflammatory processes and their complex interaction. Decoding the link between degeneration and inflammation is one of the most exciting approaches in understanding OA pathophysiology and holds the promise to open new therapeutic avenues. The overarching goal of this project was to analyze the impact of mononuclear cells (MNC) on enzymatic chondrodestructive processes (MMP/ADAMTS) in OA. Synovial membrane (SM), articular cartilage (AC) and peripheral blood (PB) were obtained from a total of 21 patients with advanced knee OA who underwent arthroplastic surgery. In supernatants of native synovial cell cultures, T cell-depleted synovial cell cultures and macrophage-depleted synovial cell cultures, the concentrations of various metalloproteinases were examined by Enzyme Linked Immunosorbent Assay (ELISA). Furthermore, ELISA was used to analyze concentrations of metalloproteinases in supernatants of chondrocyte monocultures and chondrocyte co-cultures with CD4+CD127dim/- enriched peripheral blood mononuclear cells (PBMC), Treg depleted CD4+CD25-CD127dim/- enriched PBMC and CD4+CD25+CD127dim/- Treg. Compared to native synovial cell culture, T cell depletion led to significantly lower levels of MMP1, MMP3 and MMP-9 and macrophage depletion led to a significant decline of MMP1, MMP3, MMP9 and ADAMTS-5 concentration. Compared to T cell depletion, macrophage depletion resulted in a significantly stronger reduction of MMP1, MMP3, MMP9 and ADAMTS5. In chondrocyte co-culture with CD4+CD127dim/- enriched PBMC the concentration of MMP1 and ADAMTS5 was significantly increased compared to chondrocyte monoculture. No significant differences were found between chondrocyte monoculture and chondrocyte coculture with Treg as well as between co-culture with CD4+CD127dim/- enriched PBMC containing Treg and co-culture with Treg-depleted CD4+CD25-CD127dim/- enriched PBMC. In conclusion, our data suggests that both synovial macrophages and T cells have a catabolic potential by inducing the release of chondrodestructive metalloproteinases in OA synovium. This study also supports the hypothesis that MNC affect the release of metalloproteinases by chondrocytes and are hereby involved in the cartilageinduced chondrodestructive process. In this study no suppressive effect of Treg was shown.

Blood Metal Ion Release After Primary Total Knee Arthroplasty: A Prospective Study.

OBJECTIVES: To investigate the course of in vivo blood metal ion levels in patients undergoing primary total knee arthroplasty (TKA) and to investigate potential risk factors associated with metal ion release in these patients. METHODS: Twenty-five patients with indication for TKA were included in this prospective study. Whole blood metal ion analysis was performed pre-operatively and at 1 week, 6 weeks, 3 months, 6 months, and 12 months postoperatively. Clinical scores were obtained using the American Knee Society Score (AKSS) and the Oxford Knee Score (OKS) at each follow-up and patients' activity levels were assessed by measuring the mean annual walking cycles at 12 months follow-up. Anteroposterior and lateral radiographs of the operated knee were evaluated postoperatively and at 12-month follow-up with regard to implant position and radiological signs of implant loosening. Correlation analysis using multivariate linear regression was performed to investigate the influence of different variables (age, gender, functional scores, number of walking cycles, and body mass index [BMI]) on blood cobalt ion concentrations. RESULTS: Mean metal ion levels of cobalt, chromium, molybdenum, and titanium were 0.28 µg/L (SD, 0.14), 0.43 µg/L (SD, 0.49), 0.62 µg/L (SD, 0.45), and 1.96 µg/L (SD, 0.98), respectively at 12-month follow-up. Mean cobalt ion levels significantly increased 1-year after surgery compared to preoperative measurements. There was no statistically significant increase of mean metal ion levels of chromium, titanium, and molybdenum at 1-year follow-up. Overall, metal ion levels were low and no patient demonstrated cobalt ion levels above 1 µg/L. Postoperative radiographs demonstrated well-aligned TKAs in all patients and no signs of osteolysis or implant loosening were detected at 1-year follow-up. Both the AKSS and OKS significantly improved during the course of the study up to the final follow-up. Multivariate regression analysis did not show a statistically significant correlation between the tested variables and blood cobalt ion concentrations. CONCLUSION: A statistically significant increase of mean cobalt ion concentration at 1-year follow-up was found in this cohort of patients with well-functioning TKA, although overall blood metal ion levels were relatively low. Despite low systemic metal ion concentrations seen in this cohort, the local effects of increased metal ion concentrations in the periprosthetic environment on the long-term outcome of TKA should be further investigated.