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.

Reducing Blood Loss in Revision Total Hip and Knee Arthroplasty: Tranexamic Acid Is Effective in Aseptic Revisions and in Second-Stage Reimplantations for Periprosthetic Infection.

INTRODUCTION: The aim of the study was to determine the usefulness of tranexamic acid (TXA) in revision total hip arthroplasty (rTHA) and revision total knee arthroplasty (rTKA). We analyzed the perioperative blood loss with and without TXA in aseptic rTHA and rTKA as well as in second-stage reimplantation for hip and knee periprosthetic infection. MATERIALS AND METHODS: In this prospective cohort study, 147 patients receiving TXA (96 rTHA, 51 rTKA) were compared to a retrospective cohort of 155 patients without TXA (103 rTHA, 52 rTKA). The TXA regimen consisted of a preoperative bolus of 10 mg/kg bodyweight (BW) TXA plus 1 mg/kgBW/h perioperatively. Given blood products were documented and the perioperative blood loss was calculated. Thromboembolic events were registered until three months postoperatively. In subgroups, the effects of TXA were separately analyzed in 215 aseptic revisions as well as in 87 reimplantations in two-stage revisions for periprosthetic infection. RESULTS: Both TXA groups showed a significantly reduced mean blood loss compared to the respective control groups. The TXA group of rTHA patients had a mean blood loss of 2916 ml ± 1226 ml versus 3611 ml ± 1474 ml in the control group (p<.001). For the TXA group of rTKA patients, mean calculated blood loss was 2756 ml ± 975 ml compared to 3441 ml ± 1100 ml in the control group (p=.0012). A significantly reduced blood loss was also found in the TXA subgroups for aseptic and septic revision procedures. No thromboembolic events were recorded among the TXA groups. CONCLUSIONS: There is a significant reduction of perioperative blood loss under TXA influence without an increased incidence of adverse events. The standard use of TXA can be recommended in aseptic hip and knee revision arthroplasties as well as in second-stage reimplantations for periprosthetic infection.

Minimally invasive Oxford medial unicompartmental knee arthroplasty in young patients.

PURPOSE: Advanced knee arthritis in young patients is a challenging problem that may necessitate surgical treatment. There are few published studies of mobile-bearing unicompartmental knee arthroplasty (UKA) in young patients, while indications have expanded to its use in this demanding patient group. METHODS: The clinical and radiographic results of the first 118 consecutive Oxford medial UKAs (OUKA) using a minimally invasive technique (phase 3) in 101 patients 60 years of age or younger at the time of surgery were evaluated. Median age at surgery was 57 (25-60) years. Kaplan-Meier survivorship analysis was used to estimate implant survival. RESULTS: Mean time of follow-up evaluation was five (SD 1.6) years. At final follow-up, three patients (three knees) had died, and two patients (three knees) were lost to follow-up. Five knees were revised: three for unexplained pain, one for early infection and one for bearing fracture. There was one impending revision for progression of osteoarthritis in the lateral compartment. The radiographic review demonstrated that 5 % of the knees had progressive arthritis in the lateral knee compartment, of those 2 % with full joint space loss and pain. The Kaplan-Meier survival analysis, using revision for any reason as the endpoint, estimated the five-year survival rate at 97 % (95 % CI 91-99). Ninety-six per cent of the non-revised patients were satisfied with the outcome, and 4 % were dissatisfied. The mean Oxford knee score was 41 (SD 7), with 6 % of the knees having a poor result. The mean AKSS was 89 (SD 14), mean flexion was 129° (SD 13) and the mean UCLA score was 6.8 (SD 1.5). CONCLUSION: Minimally invasive Oxford medial UKA was reliable and effective in this young and active patient cohort providing high patient satisfaction at mid-term follow-up. Progressive arthritis in the lateral knee compartment was a relevant failure mode in this age group. Most revisions were performed for unexplained pain, while we did not find loosening or wear in any patient. LEVEL OF EVIDENCE: IV.

Quality-controlled dose-reduction of pelvic X-ray examinations in infants with hip dysplasia.

BACKGROUND: Digital plain radiography (DR) examinations of the pelvis are frequently performed in infants with hip dysplasia. OBJECTIVE: The purpose was to reduce the radiation dose and to determine objective quality control criteria to ensure accurate assessment. This seems feasible because of higher quantum efficiency of DR and easy assessable anatomical structures for most orthopaedic measurements. MATERIALS AND METHODS: Institutional review board approval was obtained. In this prospective randomized study, 264 patients underwent X-ray examination of the pelvis with standard and reduced dose. The evaluation of the plain-radiographs was conducted using the following criteria: acetabular and center edge angle, closing of the epiphyseal plates and maturation of the femoral head. Two radiologists evaluated these criteria using a score ranging from 1 (definitely assessable) to 4 (not assessable). If a single criterion had been evaluated with a score of 3 or more points or more than 2 criteria with 2 points, the radiograph was scored as "not assessable". The statistical analysis was conducted as non-inferiority-trial. RESULTS: Five (1.9%) examined X-rays were scored as not assessable. There was no statistical inferiority between the examinations with standard (4.57 µSv) or reduced dose (3.06 µSv). Also, the individual evaluation of the defined criteria was dose-independent. CONCLUSION: The adequate evaluation of hip dysplasia in children and young adults on pelvic radiographs is possible with reduced radiation dose, by simple using an exposure class of 800 instead of 400.

Bacterial Infection and Implant Loosening in Hip and Knee Arthroplasty: Evaluation of 209 Cases.

The aim of this study was to evaluate bacteria species detected in a large number of patients treated for prosthetic joint infection of the hip and knee at a single specialized center. Furthermore, the rate of implant loosening was investigated in a time-dependent manner for the most frequently detected bacteria species. A retrospective analysis of patients (n = 209) treated for prosthetic joint infection of the hip and knee was performed. The following parameters were evaluated: C-Reactive Protein (CRP) concentration, microbiological evaluation of tissue samples, loosening of the implant, the time that had elapsed since the primary prosthetic joint replacement, and the duration since the last surgical intervention. Coagulase-negative Staphylococcus spp. were most frequently detected, followed by Staphylococcus aureus. Differences in CRP concentration were detected among various bacteria species. Osteolysis was not associated with one causative agent in particular. Patients who had undergone previous revision surgery had a higher probability of implant loosening. Coagulase-negative Staphylococcus spp. are the most common causative agents of prosthetic joint infection and show no significant differences with regard to implant loosening or the time-course when compared to S. aureus. Infections with Enterococcus spp. seem to develop faster than with other bacteria species. The risk of implant loosening increases with revision surgery, in particular in the hip joint.

Cortical hypertrophy with a short, curved uncemented hip stem does not have any clinical impact during early follow-up.

BACKGROUND: Short stems have become more and more popular for cementless total hip arthroplasty in the past few years. While conventional, uncemented straight stems for primary total hip arthroplasty (THA) have shown high survival rates in the long term, it is not known whether uncemented short stems represent a reasonable alternative. As cortical hypertrophy has been reported for short stems, the aim of this study was to determine the radiographic prevalence of cortical hypertrophy and to assess the clinical outcome of a frequently used short, curved hip stem. METHODS: We retrospectively studied the clinical and radiographic results of our first 100 consecutive THAs (97 patients) using the Fitmore® hip stem. Mean age at the time of index arthroplasty was 59 years (range, 19 - 79 years). Clinical outcome and radiographic results were assessed with a minimum follow-up of 2 years, and Kaplan-Meier survivorship analysis was used to estimate survival for different endpoints. RESULTS: After a mean follow-up of 3.3 years (range, 2.0 - 4.4 years), two patients (two hips) had died, and three patients (four hips) were lost to follow-up. Kaplan-Meier analysis estimated a survival rate of 100 % at 3.8 years, with revision for any reason as the endpoint. No femoral component showed radiographic signs of loosening. No osteolysis was detected. Cortical hypertrophy was found in 50 hips (63 %), predominantly in Gruen zone 3 and 5. In the cortical hypertrophy group, two patients (two hips; 4 %) reported some thigh pain in combination with pain over the greater trochanter region during physical exercise (UCLA Score 6 and 7). There was no significant difference concerning the clinical outcome between the cortical hypertrophy and no cortical hypertrophy group. CONCLUSIONS: The survival rate and both clinical and the radiographic outcome confirm the encouraging results for short, curved uncemented stems. Postoperative radiographs frequently displayed cortical hypertrophy but it had no significant effect on the clinical outcome in the early follow-up. Further clinical and radiographic follow-up is necessary to detect possible adverse, long-term, clinical effects of cortical hypertrophy.

CD8+/FOXP3+-ratio in osteosarcoma microenvironment separates survivors from non-survivors: a multicenter validated retrospective study.

Osteosarcoma is the most common primary bone tumor characterized by juvenile onset, tumor heterogeneity, and early pulmonary metastasis. Therapeutic improvement stagnates since more than two decades. Unlike major malignancies, biomarkers as prognostic factors at time of diagnosis are missing. Disease rareness hampers study recruitment of patient numbers sufficient to outweigh tumor heterogeneity. Here, we analyzed in a multicenter cohort the osteosarcoma microenvironment to reduce effects of tumor cell heterogeneity. We hypothesized that quantitative ratios of intratumoral CD8+T-cells to FOXP3+T-cells (CD8+/FOXP3+-ratios) provide strong prognostic information when analyzed by whole-slide imaging in diagnostic biopsies. We followed recommendations-for-tumor-marker-prognostic-studies (REMARK). From 150 included cases, patients with complete treatment were identified and assigned to the discovery (diagnosis before 2004) or the validation cohort (diagnosis 2004-2012). Highly standardized immunohistochemistry of CD8+ and FOXP3+, which was validated by methylation-specific gene analysis, was performed followed by whole-slide analysis and clinical outcome correlations. We observed improved estimated survival in patients with CD8+/FOXP3+-ratios above the median (3.08) compared to patients with lower CD8+/FOXP3+-ratios (p = 0.000001). No patients with a CD8+/FOXP3+-ratio above the third quartile died within the observation period (median follow-up 69 mo). Multivariate analysis demonstrated independence from current prognostic factors including metastasis and response to neoadjuvant chemotherapy. Data from an independent validation cohort confirmed improved survival (p = 0.001) in patients with CD8+/FOXP3+-ratios above 3.08. Multivariate analysis proofed that this observation was also independent from prognostic factors at diagnosis within the validation cohort. Intratumoral CD8+/FOXP3+-ratio in pretreatment biopsies separates patients with prolonged survival from non-survivors in osteosarcoma.

Unicompartmental knee arthroplasty in patients with full versus partial thickness cartilage loss (PTCL): equal in clinical outcome but with higher reoperation rate for patients with PTCL.

PURPOSE: While the classical indications and contraindications for unicondylar knee arthroplasty (UKA) are widely accepted there is not yet consensus if patients with partial thickness cartilage loss (PTCL) are equally suited for treatment with UKA. The aim of our study was to determine if patients with partial thickness cartilage loss do equally well after treatment with UKA. METHODS: The study retrospectively analyzed the clinical results as well as the survival rates of 64 patients treated with UKA with the medial Oxford knee system. 32 patients had shown PTCL on preoperative radiographs, while the matched control group presented with full thickness cartilage loss (FTCL) medially. Outcome parameters were the Oxford Knee Score (OKS), the American Knee Society Score (AKS), and radiographic analysis. RESULTS: Postoperative improvement in OKS was 16 (SD 9.0) for patients with PTCL and 17 (SD 8.1) for patients with FTCL. There were no significant differences in the clinical scores between the two groups. Five Patients with PTCL had reoperation whereas there were only two in the bone on bone group. Cumulative survival at 5 years for all revisions was 84 % (95 % CI 72-92 %) for the PTCL group and 97 % (95 % CI 92-100 %) for the FTCL group. This difference was not yet significant (log rank: p = 0.095). CONCLUSIONS: Patients with PTCL are not equally suited for treatment with UKA like patients with bone on bone. Although PTCL has equal clinical results, it was associated with higher revision rates in our series.

Pelvic X-ray examinations in follow-up of hip arthroplasty or femoral osteosynthesis--dose reduction and quality criteria.

OBJECTIVE: Digital plain radiographs of the pelvis are frequently performed in follow-up examinations of patients who received total hip arthroplasty (THA) or osteosynthesis (OS). Thus, the purpose was to reduce the radiation dose and to determine objective quality control criteria to ensure accurate assessment. MATERIALS AND METHODS: Institutional review board approval was obtained. In this prospective randomized study, 289 patients underwent X-ray examination of the pelvis as follow up after receiving THA or OS with standard and reduced dose. The evaluation of the plain radiographs was conducted using the following criteria: bone-implant interface, implant-implant discrimination, implant-surface character and periarticular heterotopic ossification. Two radiologists evaluated these criteria using a score ranging from 1 (definitely assessable) to 4 (not assessable). If a single criterion had been evaluated with a score of 3 or more or more than 2 criteria with 2 points, the radiograph was scored as "not assessable". The study was designed as non-inferiority-trial. RESULTS: Seven (2.4%) examined X-rays were scored as not assessable. There was no statistical inferiority between the examinations with standard (0.365 mSv) or reduced dose (0.211 mSv). Reduced dose only led to limitations in the evaluation of ceramic components with low clinical impact in most scenarios. CONCLUSION: Plain radiography of the pelvis in patients with THA or OS can be performed with a dose reduction of about 42% without a loss of important information. The obtained quality control criteria were clinically applicable.

Do overhead sports increase risk for rotator cuff tears in wheelchair users?

OBJECTIVE: To analyze whether frequent overhead-sports activity increases the risk for rotator cuff disease in patients with spinal cord injuries (SCIs) who are wheelchair dependent. DESIGN: Cross-sectional study, risk analysis. SETTING: Department of Orthopaedic Surgery, Trauma Surgery and Spinal Cord Injury. PARTICIPANTS: Patients (N=296) with SCI requiring the full-time use of a manual wheelchair were recruited for this study. The total population was divided into 2 groups (sports vs no sports), among them 103 patients playing overhead sports on a regular basis (at least 1-2 times/wk) and 193 patients involved in overhead sports less than once a week or in no sports activity at all. The mean age of the sports group was 49.1 years. The mean duration of wheelchair dependence was 26.5 years. The mean age of the no-sports group was 48 years. The mean duration of wheelchair dependence was 25.2 years. Each individual completed a questionnaire designed to identify overhead-sports activity on a regular basis and was asked about shoulder problems. Magnetic resonance imaging scans of both shoulders were performed in each patient and analyzed in a standardized fashion. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Possible differences in continuous data between patients with and without rotator cuff tear were evaluated. The relative risk of suffering from a rotator cuff tear between patients playing overhead sports and those not playing overhead sports was calculated. RESULTS: One hundred three patients played overhead sports regularly and 193 did not. There was no difference between groups regarding age, sex, level of SCI, and duration of wheelchair dependence. The body mass index was significantly lower in the sports group than in the no-sports group (P<.0001). A rotator cuff tear was present in 75.7% of the patients in the sports group and in 36.3% of the patients in the no-sports group (P<.0001). Rotator cuff tears were symptomatic in 92.6% of the patients. The estimated risk increase for the sports group to develop rotator cuff tears was twice as high as for the no-sports group (95% confidence interval, 1.7-2.6; P<.001). Similar results were found for the neurological level of lesion (T2-7/

Improved survival in osteosarcoma patients with atypical low vascularization.

BACKGROUND: Osteosarcoma is considered a highly vascularized bone tumor with early metastatic dissemination through intratumoral blood vessels mostly into the lung. Novel targets for therapy such as tumor vascularization are highly warranted since little progress has been achieved in the last 30 years. However, proof of relevance for vascularization as a major prognostic parameter has been hampered by tumor heterogeneity, difficulty in detecting microvessels by immunohistochemistry, and small study cohorts. Most recently, we demonstrated that highly standardized whole-slide imaging could overcome these limitations (Kunz et al., PloS One 9(3):e90727, 2014). In this study, we applied this method to a multicenter cohort of 131 osteosarcoma patients to test osteosarcoma vascularization as a prognostic determinant. METHODS: Computer-assisted whole-slide analysis, together with enzymatic epitope retrieval, was used for CD31-based microvessel quantification in 131 pretreatment formalin-fixed and paraffin-embedded biopsies from three bone tumor centers. Kaplan-Meier-estimated survival and chemoresponse were determined and multivariate analysis was performed. Conventional hot-spot-based microvessel density (MVD) determination was compared with whole-slide imaging. RESULTS: We detected high estimated overall (p ≤ 0.008) and relapse-free (p ≤ 0.004) survival in 25 % of osteosarcoma patients with low osteosarcoma vascularization in contrast to other patient groups. Furthermore, all patients with low osteosarcoma vascularization showed a good response to neoadjuvant chemotherapy. Comparison of conventional MVD determination with whole-slide imaging suggests false high quantification or even exclusion of samples with low osteosarcoma vascularization due to difficult CD31 detection in previous studies. CONCLUSION: Low intratumoral vascularization at the time of diagnosis is a strong predictor for prolonged survival and good response to neoadjuvant chemotherapy in osteosarcoma.

Pain threshold correlates with functional scores in osteoarthritis patients.

BACKGROUND AND PURPOSE: Pain sensitization may be one of the reasons for persistent pain after technically successful joint replacement. We analyzed how pain sensitization, as measured by quantitative sensory testing, relates preoperatively to joint function in patients with osteoarthritis (OA) scheduled for joint replacement. PATIENTS AND METHODS: We included 50 patients with knee OA and 49 with hip OA who were scheduled for joint replacement, and 15 control participants. Hip/knee scores, thermal and pressure detection, and pain thresholds were examined. RESULTS: Median pressure pain thresholds were lower in patients than in control subjects: 4.0 (range: 0-10) vs. 7.8 (4-10) (p = 0.003) for the affected knee; 4.5 (2-10) vs. 6.8 (4-10) (p = 0.03) for the affected hip. Lower pressure pain threshold values were found at the affected joint in 26 of the 50 patients with knee OA and in 17 of the 49 patients with hip OA. The American Knee Society score 1 and 2, the Oxford knee score, and functional questionnaire of Hannover for osteoarthritis score correlated with the pressure pain thresholds in patients with knee OA. Also, Harris hip score and the functional questionnaire of Hannover for osteoarthritis score correlated with the cold detection threshold in patients with hip OA. INTERPRETATION: Quantitative sensory testing appeared to identify patients with sensory changes indicative of mechanisms of central sensitization. These patients may require additional pain treatment in order to profit fully from surgery. There were correlations between the clinical scores and the level of sensitization.

Quality-controlled dose reduction of full-leg radiography in patients with knee malalignment.

OBJECTIVE: Digital plain radiographs of the full leg are frequently performed examinations of children and young adults. Thus, the objective of this work was to reduce the radiation exposure dependent on specific indications, and to determine objective quality-control criteria to ensure accurate assessment. MATERIALS AND METHODS: Institutional review board approval and informed consent of all participants were obtained. In this prospective, randomized controlled, blinded, two-armed single-center study, 288 evaluable patients underwent plain radiography of the full leg with standard and reduced doses. The evaluation of the plain radiographs was conducted using the following criteria: mechanical axis, leg length, and maturation of the epiphyseal plate. Two blinded radiologists evaluated these criteria using a score ranging from 1 (definitely assessable) to 4 (not assessable). If a single criterion had been evaluated with a score of 3 or more points or all criteria with 2 points, the radiograph was scored as "not assessable". The study was designed as a non-inferiority trial. RESULTS: Eleven (3.8%) examined X-rays were scored as not assessable. The rate of non-assessable radiographs with 33% reduced dose was significantly not inferior to the rate of non-assessable radiographs with standard dose. The evaluation of the quality criteria was dose independent. CONCLUSIONS: Full-leg plain radiography in patients with knee malalignment can be performed at 33% reduced dose without loss of relevant diagnostic information.

Evaluation of implant sonication as a diagnostic tool in implant-associated infections.

Infections of implants pose a severe problem in the field of orthopedic surgery, because they can cause bone degradation with subsequent loosening of the implant. The discrimination between septic implant loosening and aseptic loosening can be a challenge, and hence novel diagnostic methods have been introduced to improve the detection of bacteria. Because a major problem is their firm adherence to implants due to biofilm formation, sonication has been introduced, followed by identification of bacteria by culture or genetic methods. In this study, we compared the results obtained after sonication pretreatment with those of microbiological testing of tissue samples and histopathological evaluation of the same tissue. Furthermore, we related the results obtained following sonication to the clinical diagnosis of septic or aseptic implant loosening, respectively. Sonication of explanted devices also enhances the likelihood of detecting bacterial growth in patients who were considered "aseptic" based on the clinical evaluation.

10-year results of the uncemented Allofit press-fit cup in young patients.

BACKGROUND AND PURPOSE: Uncemented acetabular components in primary total hip arthroplasty (THA) are commonly used today, but few studies have evaluated their survival into the second decade in young and active patients. We report on a minimum 10-year follow-up of an uncemented press-fit acetabular component that is still in clinical use. METHODS: We examined the clinical and radiographic results of our first 121 consecutive cementless THAs using a cementless, grit-blasted, non-porous, titanium alloy press-fit cup (Allofit; Zimmer Inc., Warsaw, IN) without additional screw fixation in 116 patients. Mean age at surgery was 51 (21-60) years. Mean time of follow-up evaluation was 11 (10-12) years. RESULTS: At final follow-up, 8 patients had died (8 hips), and 1 patient (1 hip) was lost to follow-up. 3 hips in 3 patients had undergone acetabular revision, 2 for deep infection and 1 for aseptic acetabular loosening. There were no impending revisions at the most recent follow-up. We did not detect periacetabular osteolysis or loosening on plain radiographs in those hips that were evaluated radiographically (n = 90; 83% of the hips available at a minimum of 10 years). Kaplan-Meier survival analysis using revision of the acetabular component for any reason (including isolated inlay revisions) as endpoint estimated the 11-year survival rate at 98% (95% CI: 92-99). INTERPRETATION: Uncemented acetabular fixation using the Allofit press-fit cup without additional screws was excellent into early in the second decade in this young and active patient cohort. The rate of complications related to the liner and to osteolysis was low.

Osteosarcoma microenvironment: whole-slide imaging and optimized antigen detection overcome major limitations in immunohistochemical quantification.

BACKGROUND: In osteosarcoma survival rates could not be improved over the last 30 years. Novel biomarkers are warranted to allow risk stratification of patients for more individual treatment following initial diagnosis. Although previous studies of the tumor microenvironment have identified promising candidates, novel biomarkers have not been translated into routine histopathology. Substantial difficulties regarding immunohistochemical detection and quantification of antigens in decalcified and heterogeneous osteosarcoma might largely explain this translational short-coming. Furthermore, we hypothesized that conventional hot spot analysis is often not representative for the whole section when applied to heterogeneous tissues like osteosarcoma. We aimed to overcome these difficulties for major biomarkers of the immunovascular microenvironment. METHODS: Immunohistochemistry was systematically optimized for cell surface (CD31, CD8) and intracellular antigens (FOXP3) including evaluation of 200 different antigen retrieval conditions. Distribution patterns of these antigens were analyzed in formalin-fixed and paraffin-embedded samples from 120 high-grade central osteosarcoma biopsies and computer-assisted whole-slide analysis was compared with conventional quantification methods including hot spot analysis. RESULTS: More than 96% of osteosarcoma samples were positive for all antigens after optimization of immunohistochemistry. In contrast, standard immunohistochemistry retrieved false negative results in 35-65% of decalcified osteosarcoma specimens. Standard hot spot analysis was applicable for homogeneous distributed FOXP3+ and CD8+ cells. However, heterogeneous distribution of vascular CD31 did not allow reliable quantification with hot spot analysis in 85% of all samples. Computer-assisted whole-slide analysis of total CD31- immunoreactive area proved as the most appropriate quantification method. CONCLUSION: Standard staining and quantification procedures are not applicable in decalcified formalin-fixed and paraffin-embedded samples for major parameters of the immunovascular microenvironment in osteosarcoma. Whole-slide imaging and optimized antigen retrieval overcome these limitations.

On the inflammatory response in metal-on-metal implants.

BACKGROUND: Metal-on-metal implants are a special form of hip endoprostheses that despite many advantages can entail serious complications due to release of wear particles from the implanted material. Metal wear particles presumably activate local host defence mechanisms, which causes a persistent inflammatory response with destruction of bone followed by a loosening of the implant. To better characterize this inflammatory response and to link inflammation to bone degradation, the local generation of proinflammatory and osteoclast-inducing cytokines was analysed, as was systemic T cell activation. METHODS: By quantitative RT-PCR, gene expression of cytokines and markers for T lymphocytes, monocytes/macrophages and osteoclasts, respectively, was analysed in tissue samples obtained intraoperatively during exchange surgery of the loosened implant. Peripheral T cells were characterized by cytofluorometry before surgery and 7 to 10 days thereafter. RESULTS: At sites of osteolysis, gene expression of cathepsin K, CD14 and CD3 was seen, indicating the generation of osteoclasts, and the presence of monocytes and of T cells, respectively. Also cytokines were highly expressed, including CXCL8, IL-1ß, CXCL2, MRP-14 and CXCL-10. The latter suggest T cell activation, a notion that could be confirmed by detecting a small, though conspicuous population of activated CD4+ cells in the peripheral blood T cells prior to surgery. CONCLUSION: Our data support the concept that metallosis is the result of a local inflammatory response, which according to histomorphology and the composition of the cellular infiltrate classifies as an acute phase of a chronic inflammatory disease. The proinflammatory environment, particularly the generation of the osteoclast-inducing cytokines CXCL8 and IL1-ß, promotes bone resorption. Loss of bone results in implant loosening, which then causes the major symptoms of metallosis, pain and reduced range of motion.

Primary stability of the Fitmore stem: biomechanical comparison.

PURPOSE: After clinical introduction of the Fitmore stem (Zimmer), we noticed the formation of cortical hypertrophies in a few cases. We questioned whether (1) the primary stability or (2) load transfer of the Fitmore stem differs from other stems unassociated with the formation of hypertrophies. We compared the Fitmore stem to the well-established CLS stem. METHODS: Four Fitmore and four CLS stems were implanted in eight synthetic femurs. A cyclic torque around the stem axis and a mediolateral cyclic torque were applied. Micromotions between stems and femurs were measured to classify the specific rotational implant stability and to analyse the bending behaviour of the stem. RESULTS: No statistical differences were found between the two stem designs with respect to their rotational stability (p = 0.82). For both stems, a proximal fixation was found. However, for the mediolateral bending behavior, we observed a significantly (p < 0.01) higher flexibility of the CLS stem compared to the Fitmore stem. CONCLUSION: Hip stem implantation may induce remodelling of the periprosthetic bone structure. Considering the proximal fixation of both stems, rotational stability of the Fitmore® stem might not be a plausible explanation for clinically observed formation of hypertrophies. However, bending results support our hypothesis that the CLS stem presumably closely follows the bending of the bone, whereas the shorter Fitmore stem acts more rigidly. Stem rigidity and flexibility needs to be considered, as they may influence the load transfer at the implant-bone interface and thus possibly affect bone remodelling processes.

Minimum ten-year results of a 28-mm metal-on-metal bearing in cementless total hip arthroplasty in patients fifty years of age and younger.

PURPOSE: Concerns have been raised in relation to metal-on-metal (MoM) articulations with catastrophic soft-tissue reactions due to metal debris. We reviewed how small head MoM articulations perform in primary uncemented total hip arthroplasty (THA) in young patients at a minimum of ten years. METHODS: We retrospectively evaluated the clinical and radiographic results of the first 100 consecutive primary cementless THAs using the 28-mm Metasul MoM articulation in 91 patients younger than 50 years of age at the time of surgery. RESULTS: After 13 years, survival for the endpoint revision due to any reason was 90.9 % and 98.9 % for revision due to aseptic implant loosening. The cumulative incidence of MoM related revisions was 1.2 %. Small proximal femoral osteolysis was found in 18 % of hips. No acetabular osteolysis or loosening was detected. Two hips showed signs of femoral neck impingement with severe damage to the neck. CONCLUSIONS: Early in the second decade, MoM-associated complications were rare using the 28-mm Metasul articulation, and aseptic loosening was not a major mode of failure in this cohort of young patients. LEVEL OF EVIDENCE: Therapeutic Level IV.

CT-guided radiofrequency ablation of osteoid osteoma: correlation of clinical outcome and imaging features.

PURPOSE: We aimed to retrospectively evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of patients with osteoid osteoma treated with CT-guided radiofrequency ablation (RFA) along with the clinical outcome and long-term success. MATERIALS AND METHODS: Seventy-three CT-guided RFA procedures were performed in 72 patients. The long-term success was assessed using a questionnaire including several visual analog scale scores. The CT evaluation included pre- and immediate postprocedural imaging of all 72 patients, and MRI was performed in 18 patients with follow-up imaging (mean, 3.4±2.2 months). The evaluation criteria included nidus morphology and a correlation with markers of clinical success. RESULTS: The primary technique effectiveness rate was 71/72 (99%). One relapse was successfully retreated, leading to a secondary technique effectiveness rate of 72/72 (100%). The long-term follow-up (mean, 51.2±31.2 months; range, 3-109 months) revealed a highly significant reduction of all assessed limitation scores (P < 0.001). The CT morphology was typical in all cases and did not change during the short-term follow-up. The follow-up MRI patterns varied considerably, including persistent nidus contrast enhancement in one-third (6/18) and persistent marrow edema in half (9/18) of the patients. None of the investigated MRI and CT patterns correlated with the clinical outcome. CONCLUSION: The long-term outcome of CT-guided RFA of osteoid osteoma is excellent. There is no correlation of the CT and MRI patterns with the clinical outcome. Thus, the treatment decisions should not be solely based on the imaging findings. Investigators should also be aware of the variety of imaging patterns after RFA.