Sascha Gravius

Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty.

Unyvero i60 implant and tissue infection (ITI) multiplex PCR system in diagnosing periprosthetic joint infection.

Periprosthetic joint infection (PJI) is one of the most challenging complications in orthopedic surgery. In cases of suspected periprosthetic joint infection several diagnostic methods are available. In this study we investigated the performance of the newly available Unyvero i60 implant and tissue infection (ITI) multiplex PCR System. 62 specimens from 31 patients with suspected PJI or aseptic loosening of a painful joint arthoplasty were included in this study. Besides the established diagnostic procedures we included a commercial multiplex PCR detection system for diagnosis of PJI. The PCR results obtained from analysis of sonication and synovial fluids (62 specimens) showed a sensitivity of 66.7%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 68.4% when compared to cultural methods. Notably, cultures from sonication fluid displayed a sensitivity of 88.9%, a specificity of 61.5%, a PPV of 76.2% and a NPV of 80.0% when compared to tissue cultures. In conclusion, multiplex PCR is an additional - rapid - method for diagnosing PJI. Positive results with the PCR assay used in this study were always confirmed by subsequent matching culture positivity. However, apart from the time saved the nucleic acid amplification technique did not yield additional information than that obtained from microbiological cultures.

The Effect of Dexamethasone and Triiodothyronine on Terminal Differentiation of Primary Bovine Chondrocytes and Chondrogenically Differentiated Mesenchymal Stem Cells

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal differentiation, they can be used to generate a model of endochondral ossification, but this limitation must be kept in mind when using them in cartilage tissue engineering application.

Uncemented femoral revision arthroplasty using a modular tapered, fluted titanium stem: 5- to 16-year results of 163 cases

Background and purpose — Due to the relative lack of reports on the medium- to long-term clinical and radiographic results of modular femoral cementless revision, we conducted this study to evaluate the medium- to long-term results of uncemented femoral stem revisions using the modular MRP-TITAN stem with distal diaphyseal fixation in a consecutive patient series. Patients and methods — We retrospectively analyzed 163 femoral stem revisions performed between 1993 and 2001 with a mean follow-up of 10 (5–16) years. Clinical assessment included the Harris hip score (HHS) with reference to comorbidities and femoral defect sizes classified by Charnley and Paprosky. Intraoperative and postoperative complications were analyzed and the failure rate of the MRP stem for any reason was examined. Results — Mean HHS improved up to the last follow-up (37 (SD 24) vs. 79 (SD 19); p < 0.001). 99 cases (61%) had extensive bone defects (Paprosky IIB–III). Radiographic evaluation showed stable stem anchorage in 151 cases (93%) at the last follow-up. 10 implants (6%) failed for various reasons. Neither a breakage of a stem nor loosening of the morse taper junction was recorded. Kaplan-Meier survival analysis revealed a 10-year survival probability of 97% (95% CI: 95–100). Interpretation — This is one of the largest medium- to long-term analyses of cementless modular revision stems with distal diaphyseal anchorage. The modular MRP-TITAN was reliable, with a Kaplan-Meier survival probability of 97% at 10 years.

Investigation of neutrophilic peptides in periprosthetic tissue by matrix-assisted laser desorption ionisation time-of-flight imaging mass spectrometry

PurposeThe accurate diagnosis of periprosthetic joint infection (PJI) relies on clinical investigation, laboratory parameters, radiological methods, sterile joint aspiration for synovial fluid leucocyte count and microbiological analysis and tissue sampling for histopathology. Due to the limits in specificity and sensitivity of these methods, molecular techniques and new biomarkers were introduced into the diagnostic procedure. Histological examination is related to the amount of neutrophils in the periprosthetic tissue in frozen sections and formalin-fixed paraffin embedded material (FFPE). However, the threshold of neutrophils per defined area of tissue among various studies is very inconsistent.MethodsWe have applied matrix-assisted laser desorption ionisation time-of-flight imaging mass spectrometry (MALDI IMS) to a total of 32 periprosthetic tissue samples of patients with PJI to detect peptides associated with areas of neutrophil infiltration.ResultsSpecific peaks associated with a high amount of neutrophils were detected. Of these m/z peaks, four could be assigned to predictive neutrophil molecules. These peptides include annexin A1, calgizzarin (S100A11), calgranulin C (S100A12) and histone H2A. By MALDI IMS, these peptides could be shown to be co-localised with the infiltration of neutrophils in the immediate vicinity of the periprosthetic interface, whereas more distant areas did not show neutrophil invasion or infection-related peptides.ConclusionsMALDI IMS is a new method allowing identification of neutrophil peptides in periprosthetic tissues and may be a surrogate for counting neutrophils as an objective parameter for PJI.

Comparison of bacterial growth in sonication fluid cultures with periprosthetic membranes and with cultures of biopsies for diagnosing periprosthetic joint infection

Total joint arthroplasty is a common operation worldwide with infection rates between 1% and 3%. In cases of suspected periprosthetic joint infection, it is very challenging to rule out the causative microorganisms. In this study, we compared the appearance of periprosthetic membranes with the microbiological results obtained from cultures of sonication fluid and the correlation between classical microbiological cultures and cultures of sonication fluid. The results confirmed a strong correlation of bacterial growth in sonication fluid cultures with bacterial growth in classical microbiological cultures. Most importantly, however, our study documented a highly significant correlation of periprosthetic membranes typical for periprosthetic joint infection (PJI) with bacterial growth in sonication fluid. Sonication fluid cultures yielded a better sensitivity than tissue cultures (72.34-60.87%). These 3 methods are useful tools in diagnosing PJIs, and even more, sonication fluid cultures should be included in the diagnostic path of PJI.

Surface-based determination of the pelvic coordinate system

In total hip replacement (THR) one technical factor influencing the risk of dislocation is cup orientation. Computer-assisted surgery systems allow for cup navigation in anatomy-based reference frames. The pelvic coordinate system most used for cup navigation in THR is based on the mid-sagittal plane (MSP) and the anterior pelvic plane (APP). From a geometrical point of view, the MSP can be considered as a mirror plane, whereas the APP can be considered as a tangent plane comprising the anterior superior iliac spines (ASIS) and the pubic tubercles. In most systems relying on the pelvic coordinate system, the most anterior points of the ASIS and the pubic tubercles are selected manually. As manual selection of landmark points is a tedious, time-consuming and error-prone task, a surface-based approach for combined MSP and APP computation is presented in this paper: Homologous points defining the MSP and the landmark points defining the APP are selected automatically from surface patches. It is investigated how MSP computation can benefit from APP computation and vice versa, and clinical perspectives of combined MSP and APP computation are discussed. Experimental results on computed tomography data show that the surface-based approach can improve accuracy.

Funktionalität und Genauigkeit eines fluoroskopischen Navigationssystems zur Implantation von Hüftkopf-Oberflächenersatzprothesen: Eine Anatomiestudie

INTRODUCTION Resurfacing arthroplasty represents an alternative method to total hip replacement especially for the young and active patient. The main reasons for early implant failure are mal-positioning of the femoral component and notching of the femoral neck during femoral head preparation. MATERIAL AND METHODS In the context of a cadaver study of formalin-fixed cadaveric full body specimens 6 DUROM -Hip-Resurfacing prosthesis have been implanted under navigation control. The aim of the study was an evaluation of the functionality and accuracy of the computer-assisted planning and navigation system on the basis of a navigation module library from Surgitaix AG Aachen, Germany. RESULTS The main angulation error between planning (135.2 +/- 3.6 degrees ) and navigation (136.2 +/- 2.8 degrees ) was 1.9 +/- 1.1 degrees , the main anterior offset error between planning (2.2 +/- 1.3 mm) and navigation (2.7 +/- 2.3 mm) was 1.2 +/- 1.9 mm. The main distance error between planning and navigation was 2.7 +/- 1.3 mm. The mean time for all five planning and navigation steps was 20.2 +/- 2.5 min. Against the background of a acetabular bone-saving approach in all 6 cases the smallest possible femoral component could be implanted. CONCLUSION The computer-assisted fluoroscopic planning and navigation system for hip resurfacing showed within the scope of this cadaver study first promising results. The system approaches a practicable intraoperative planning with a high accuracy in operative implementation. Nevertheless, the potential benefit has to be evaluated in further clinical studies, especially from the perspective of a possible integration of this navigation system into the clinical work-flow. Further studies should consider a fluoroscopic-assisted range of motion assessment under consideration of an additional cup-module to enhance the postoperative range of motion after hip resurfacing procedures.

RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening

AIM To assess serum levels of RANK-ligand (RANKL) and osteoprotegerin (OPG) as biomarkers for periprosthetic joint infection (PJI) and compare their accuracy with standard tests. METHODS One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics (joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification, patients were categorized into PJI, aseptic loosening, and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase (AP), and the bone-specific subform of AP (bAP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants. RESULTS All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL (P = 0.16) and OPG (P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI (P = 0.005). A ratio > 60 ruled out PJI in all cases (specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured (calcium, phosphate, AP, and bAP) showed a significant difference, and only AP and bAP measurements showed a tendency towards higher values in the loosened group (with P = 0.09 for AP and P = 0.19 for bAP). CONCLUSION Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.

Automatic extraction of the mid-sagittal plane using an ICP variant

Precise knowledge of the mid-sagittal plane is important for the assessment and correction of several deformities. Furthermore, the mid-sagittal plane can be used for the definition of standardized coordinate systems such as pelvis or skull coordinate systems. A popular approach for mid-sagittal plane computation is based on the selection of anatomical landmarks located either directly on the plane or symmetrically to it. However, the manual selection of landmarks is a tedious, time-consuming and error-prone task, which requires great care. In order to overcome this drawback, previously it was suggested to use the iterative closest point (ICP) algorithm: After an initial mirroring of the data points on a default mirror plane, the mirrored data points should be registered iteratively to the model points using rigid transforms. Finally, a reflection transform approximating the cumulative transform could be extracted. In this work, we present an ICP variant for the iterative optimization of the reflection parameters. It is based on a closed-form solution to the least-squares problem of matching data points to model points using a reflection. In experiments on CT pelvis and skull datasets our method showed a better ability to match homologous areas.