Perioperative management of patients with inflammatory rheumatic diseases : Updated recommendations of the German Society for Rheumatology.

BACKGROUND: Prior to surgical interventions physicians and patients with inflammatory rheumatic diseases remain concerned about interrupting or continuing anti-inflammatory medication. For this reason, the German Society for Rheumatology has updated its recommendations from 2014. METHODS: After a systematic literature search including publications up to 31 August 2021, the recommendations on the use of of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics (bDMARDs) were revised and recommendations on newer drugs and targeted synthetic (ts)DMARDs were added. RESULTS: The glucocorticoid dose should be reduced to as low as possible 2-3 months before elective surgery (in any case <10 mg/day) but should be kept stable 1-2 weeks before and on the day of surgery. In many cases csDMARDs can be continued, exceptions being a reduction of high methotrexate doses to ≤15 mg/week and wash-out of leflunomide if there is a high risk of infection. Azathioprine, mycophenolate and ciclosporin should be paused 1-2 days prior to surgery. Under bDMARDs surgery can be scheduled for the end of each treatment interval. For major interventions Janus kinase (JAK) inhibitors should be paused for 3-4 days. Apremilast can be continued. If interruption is necessary, treatment should be restarted as soon as possible for all substances, depending on wound healing. CONCLUSION: Whether bDMARDs increase the perioperative risk of infection and the benefits and risks of discontinuation remain unclear based on the currently available evidence. To minimize the risk of a disease relapse under longer treatment pauses, in the updated recommendations the perioperative interruption of bDMARDs was reduced from at least two half-lives to one treatment interval.

[Perioperative management of treatment of patients with inflammatory rheumatic diseases : Updated recommendations of the German Society of Rheumatology]. / Perioperativer Umgang mit der Therapie von Patienten mit entzündlich rheumatischen Erkrankungen : Aktualisierte Empfehlungen der Deutschen Gesellschaft für Rheumatologie.

BACKGROUND: Prior to surgical interventions physicians and patients with inflammatory rheumatic diseases remain concerned about interrupting or continuing anti-inflammatory medication. For this reason, the German Society for Rheumatology has updated its recommendations from 2014. METHODS: After a systematic literature search including publications up to 31 August 2021, the recommendations on the use of of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics (bDMARDs) were revised and recommendations on newer drugs and targeted synthetic (ts)DMARDs were added. RESULTS: The glucocorticoid dose should be reduced to as low as possible 2-3 months before elective surgery (in any case <10 mg/day) but should be kept stable 1-2 weeks before and on the day of surgery. In many cases csDMARDs can be continued, exceptions being a reduction of high methotrexate doses to ≤15 mg/week and wash-out of leflunomide if there is a high risk of infection. Azathioprine, mycophenolate and ciclosporin should be paused 1-2 days prior to surgery. Under bDMARDs surgery can be scheduled for the end of each treatment interval. For major interventions Janus kinase (JAK) inhibitors should be paused for 3-4 days. Apremilast can be continued. If interruption is necessary, treatment should be restarted as soon as possible for all substances, depending on wound healing. CONCLUSION: Whether bDMARDs increase the perioperative risk of infection and the benefits and risks of discontinuation remain unclear based on the currently available evidence. To minimize the risk of a disease relapse under longer treatment pauses, in the updated recommendations the perioperative interruption of bDMARDs was reduced from at least two half-lives to one treatment interval.

A novel micromotion measurement method to gain instructive insight into the acetabular bone-implant interface.

In total hip arthroplasty insufficient primary stability with excessive bone-implant micromotion is a major reason for aseptic loosening at the acetabular cup implant. In the literature, several methods were proposed for in vitro micromotion measurement, but none is capable of six degrees of freedom measurement at a large number of measuring points over the entire acetabular bone-implant interface, which was the aim of the current scientific work. A pin-sleeve sensor system was developed and an appropriate installing technique was incorporated. Micromotions were transmitted from the internal interface to the accessible periphery. Motion data of the sensors were optically tracked. A calculation algorithm was conceived, discretizing superimposed rotational and translational components. The method was tested and subsequently applied to a cementless revision cup implanted into an artificial hemipelvic bone featuring a typical bone defect. Using eighteen sensors in positions across the acetabular bone-implant interface, micromotion magnitudes from 59 µm ± 2 µm to 222 µm ± 5 µm were detected. Allocation of micromotion complied with case specific anticipations. The novel pin-sleeve sensors transmitted interface micromotion to the accessible periphery as desired. The measurement method enables instructive insights into three-dimensional bone-implant micromotion and may prospectively be used to evaluate different implant systems.

Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis.

Increased extracellular Ca2+ concentrations ([Ca2+]ex) trigger activation of the NLRP3 inflammasome in monocytes through calcium-sensing receptor (CaSR). To prevent extraosseous calcification in vivo, the serum protein fetuin-A stabilizes calcium and phosphate into 70-100 nm-sized colloidal calciprotein particles (CPPs). Here we show that monocytes engulf CPPs via macropinocytosis, and this process is strictly dependent on CaSR signaling triggered by increases in [Ca2+]ex. Enhanced macropinocytosis of CPPs results in increased lysosomal activity, NLRP3 inflammasome activation, and IL-1ß release. Monocytes in the context of rheumatoid arthritis (RA) exhibit increased CPP uptake and IL-1ß release in response to CaSR signaling. CaSR expression in these monocytes and local [Ca2+] in afflicted joints are increased, probably contributing to this enhanced response. We propose that CaSR-mediated NLRP3 inflammasome activation contributes to inflammatory arthritis and systemic inflammation not only in RA, but possibly also in other inflammatory conditions. Inhibition of CaSR-mediated CPP uptake might be a therapeutic approach to treating RA.

Shear stress and von Mises stress distributions in the periphery of an embedded acetabular cup implant during impingement.

As literature implies, daily activities of total hip arthroplasty (THA) patients may include movements prone to implant-implant impingement. Thus, high shear stresses may be induced at the acetabular implant-bone interface, increasing the risk of implant loosening. The aim of the current study is to determine whether or not impingement events may pose an actual risk to acetabular periprosthetic bone. An existing experimental workflow was augmented to cover complete three-dimensional strain gage measurement. von Mises and shear stresses were calculated from 1620 measured strain values, collected around a hemispherical cup implant at 2.5 mm interface distance during worst-case impingement loading. A shear stress criterion for acetabular periprosthetic bone was derived from the literature. At the impingement site, magnitudes of von Mises stress amount to 0.57 MPa and tilting shear stress amount to -0.3 MPa at 2.5 mm interface distance. Conclusion can be drawn that worst-case impingement events are unlikely to pose a risk of bone material failure in the periphery around fully integrated cementless acetabular hip implants in otherwise healthy THA patients. As numerical predictions in the literature suggested, it can now be confirmed that impingement moments are unlikely to cause acetabular implant-bone interface fixation failures.

Effects of various anchoring components and loading conditions on primary stability of acetabular revision implant.

PURPOSE: In revision total hip arthroplasty, until today, orthopaedic surgeons are missing evidence-based guidelines on cementless acetabular cup fixation. METHODS: 5 finite element models were generated featuring the following anchorage strategies: 1 short peg, 1 long peg, 2 long screws, 3 short screws and zero anchoring components for reference. The micromotions at the implant-bone interface were analyzed for 3 different loadcases, "Seated leg-crossing" (joint force 940 N, impingement force 750 N), "Normal gait" (joint force 1820 N), and "Stumbling" (joint force 4520 N). RESULTS: Within the same loadcase, percentages of interface area below 28 µm are nearly identical in all anchorage strategies. The average percentage of interface area below 28 µm is 31% for "Seated leg-crossing", 17% for "Normal gait", and 11% for "Stumbling". Maximal von Mises stresses in "Normal gait", for example, reach 12 MPa in the short peg, 48 MPa in the long peg, 15 MPa in 1 of the 2 long screws, and 85 MPa in 1 of the 3 short screws. CONCLUSIONS: Common orthopaedic practice, to use peg or screw fixation alternatively according to bone availability or other clinical aspects, can be confirmed. The short peg may be a good alternative to the long peg with regard to the preservation of bone stock. However, the current study implies that the extent of potential osseointegration depends less on the chosen anchorage strategy but strongly on postoperative loading conditions. Total hip patients should be instructed on adequate postoperative activities.

Latent Cytomegalovirus Infection in Rheumatoid Arthritis and Increased Frequencies of Cytolytic LIR-1+CD8+ T Cells.

OBJECTIVE: Leukocyte immunoglobulin-like receptor 1 (LIR-1) is up-regulated by cytomegalovirus (CMV), which in turn, has been associated with premature aging and more severe joint disease in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the expression and functional significance of LIR-1 in CMV-positive RA patients. METHODS: We determined the phenotype, cytolytic potential, CMV-specific proliferation, and HLA-G-triggered, LIR-1-mediated inhibition of interferon-γ secretion of LIR-1+ T cells in RA patients and healthy controls. RESULTS: We found increased frequencies of CD8+ T cells with CMV pp65-specific T cell receptors in CMV-positive RA patients as compared to CMV-positive healthy controls. CMV-specific CD8+ T cells in these patients were preferentially LIR-1+ and exhibited a terminally differentiated polyfunctional phenotype. The numbers of LIR-1+CD8+ T cells increased with age and disease activity, and showed high levels of reactivity to CMV antigens. Ligation of LIR-1 with soluble HLA-G molecules in vitro confirmed an inhibitory role of the molecule when expressed on CD8+ T cells in RA patients. CONCLUSION: We propose that latent CMV infection in the context of a chronic autoimmune response induces the recently described "chronic infection phenotype" in CD8+ T cells, which retains anti-infectious effector features while exhibiting autoreactive cytolytic potential. This response is likely dampened by LIR-1 to avoid overwhelming immunopathologic changes in the setting of the autoimmune disease RA. The known deficiency of soluble HLA-G in RA and the observed association of LIR-1 expression with disease activity suggest, however, that LIR-1+ T cells are insufficiently controlled in RA and are still likely to be involved in the pathogenesis of the disease.

[Surgical treatment of tibialis anterior tendon rupture]. / Operative Therapie der Tibialis-anterior-Sehnenruptur.

INTRODUCTION: Tibialis anterior tendon rupture is rare, with only a few cases and small series having been reported in the literature. In this article, cases reported in the literature from 1997-2012 are reviewed and patients treated by the author are presented. MATERIALS: Cases published from 1997-2012 needing surgical treatment for tibialis anterior tendon rupture were retrospectively reviewed. In all, 32 articles with a total of 44 reported cases and 5 patients from our own practice were included. Patient-specific data (e.g., age, trauma, secondary diagnosis, and time to surgery), surgical technique, operative result, and documented complications were also evaluated. RESULTS: The mean age (MA) of the patients (30 men and 19 women) undergoing treatment was 58 years. A total of 17 patients presented as a result of adequate trauma (MA 52) and 32 patients without or minor trauma (MA 62). In 16 patients (33 %), a primary tendon suture was selected, while in 11 patients (22 %) osseous refixation techniques were performed. In 21 patients (43 %), plastic reconstruction was necessary. Total recovery was observed in 69 % of patients (n = 34); 26 % (n = 13) had moderate limitations. Complications were reported in 12 % of cases (n = 6), thereof one re-rupture. CONCLUSION: Good to excellent results were observed in tibialis anterior tendon ruptures reconstruction. No associations between surgical treatment and outcome were observed. The selection of the surgical technique depended on rupture mechanism, location, size, tendon constitution, rupture age, and surgeon's experience.

Peripheral CD4CD8 double positive T cells with a distinct helper cytokine profile are increased in rheumatoid arthritis.

Peripheral CD4CD8 double positive (DP) T cells have been reported to play a role in several autoimmune diseases, virus infections and cancer. In rheumatoid arthritis (RA), both CD4 and CD8 single positive (SP) T cells are known to be involved in the pathogenesis, but the role of peripheral CD4CD8 DP T cells has not been investigated in detail. Anti cyclic citrullinated antibodies (ACPA) positive and ACPA negative RA patients, patients with systemic lupus erythematodes (SLE) and age matched healthy donors (HD) were enrolled in the analysis. The frequencies and phenotype of DP T cells in PBMC were investigated. In addition, DP T cells were quantified in biopsies from rheumatoid synovium. After in vitro restimulation, the cytokine production of DP T cells was investigated in cultures of PBMC. CMV specific cytokine secretion as well as proliferation was analyzed following antigen specific restimulation after an appropriate culture duration. DP T cells were found more frequently in RA patients than in healthy controls or patients with SLE. These DP T cells express αß TCRs, are of a memory phenotype and share features of both CD4 as well as CD8 SP T cells. Importantly, DP T cells were found to also be present in the rheumatoid synovium. Further characterization of DP T cells from RA patients revealed increased production of IL-21 and IL-4, implying a possible role as T helper cells. In addition, DP T cells in RA seem to contribute to the inflammatory process, because they produce significantly more IFNγ than counterparts from HD and are increased in CMV+ RA patients. Given their capacity to produce a variety of cytokines (IL4, IL21 and IFNγ), their association with ACPA positive RA and their presence in the synovium, we suggest an important role of double positive T cells in the pathogenesis of rheumatoid arthritis.

Ethanol and formaldehyde fixation irreversibly alter bones' organic matrix.

INTRODUCTION: Biomechanical tests on bones are frequently accomplished in anatomically fixed tissues. The effects of ethanol or formaldehyde based fixation in bone material properties are subject to controversial discussions, regarding their appropriateness and usability to answer clinical questioning or biomechanical issues. We hypothesized that ethanol and formaldehyde irreversibly change bone material properties, and that this effect is mainly related to the bone's organic matrix. MATERIAL AND METHODS: Fixation related alterations in material properties were investigated in six fresh and two macerated human coxal bones by means of three-dimensional laser vibrometry based modal analysis. Ethanol or formaldehyde fixation were performed in one macerated and three unfixed specimens each. Changes in specimen weight and modal frequencies related to fixation, rinsing and drying were obtained. Modal assurance criterion (MAC) values were recorded to determine altered bone anisotropy. RESULTS: Due to fixation, modal frequencies were irreversibly altered in unfixed specimens, indicating weight loss in ethanol and structural changes in formaldehyde fixed specimens. In the macerated and inorganic controls, fixation related weight and modal frequency changes were reversible by rinsing. In the unfixed specimens, bone anisotropy was irreversibly altered by both modes of fixation, whereas the fixation related changes in bony anisotropy were reversible in the macerated controls after rinsing. DISCUSSION: Anatomical fixation that includes ethanol or formaldehyde irreversibly alters material properties of unfixed bones and impacts bone anisotropic properties, caused by changes in the organic matrix. In macerated bones that exclusively consisted of inorganic mineral salts, the observed effects on material properties and anisotropy were reversible. Conclusively, anatomical fixation on basis of ethanol or formaldehyde cannot be recommended, if material characteristics close to the vital state are of interest. Modal analysis is a potential method to gain insight into material properties, revealing the influence of the organic bone matrix on coxal bone elasticity.

Validation of density-elasticity relationships for finite element modeling of human pelvic bone by modal analysis.

In total hip arthroplasty and particularly in revision surgery, computer assisted pre-operative prediction of the best possible anchorage strategy for implant fixation would be a great help to the surgeon. Computer simulation relies on validated numerical models. In the current study, three density-elasticity relationships (No. 1-3) from the literature for inhomogeneous material parameter assignment from CT data in automated finite element (FE) modeling of long bones were evaluated for their suitability for FE modeling of human pelvic bone. Numerical modal analysis was conducted on 10 FE models of hemipelvic bone specimens and compared to the gold standard provided by experimental modal analysis results from a previous in-vitro study on the same specimens. Overall, calculated resonance frequencies came out lower than measured values. Magnitude of mean relative deviation of numerical resonance frequencies with regard to measured values is lowest for the density-elasticity relationship No. 3 (-15.9%) and considerably higher for both density-elasticity relationships No. 1 (-41.1%) and No. 2 (-45.0%). Mean MAC values over all specimens amount to 77.8% (No. 1), 78.5% (No. 2), and 83.0% (No. 3). MAC results show, that mode shapes are only slightly influenced by material distribution. Calculated resonance frequencies are generally lower than measured values, which indicates, that numerical models lack stiffness. Even when using the best suited (No. 3) out of three investigated density-elasticity relationships, in FE modeling of pelvic bone a considerable underestimation of model stiffness has to be taken into account.

Tumor necrosis factor receptor type I expression of CD4+ T cells in rheumatoid arthritis enables them to follow tumor necrosis factor gradients into the rheumatoid synovium.

OBJECTIVE: The cytokine tumor necrosis factor (TNF) plays a central role in the pathogenesis of rheumatoid arthritis (RA), but its disease-specific effector mechanisms have not been fully elucidated. This study was undertaken to investigate the role of TNF in T cell accumulation and migration in the synovitic joints of RA patients. METHODS: Vital tissue sections from rheumatoid synovium were generated using a horizontally oscillating microtome and were coincubated with fluorescence-labeled CD4+ T cells. Migration was detected by fluorescence and confocal microscopy. Migrating T cells were recovered from the tissue and analyzed for phenotype. Chemotaxis of CD4+ T cells from RA patients in response to increasing concentrations of TNF was analyzed in Transwell experiments. RESULTS: CD4+ T cells from RA patients migrated into the tissue sections in significantly higher numbers than T cells from healthy controls. Migrating CD4+ T cells differed from nonmigrating ones in their increased expression of TNF receptor type I (TNFRI), which was expressed on a fraction of circulating CD4+ T cells from RA patients, but not from controls. CD4+ T cells from the peripheral blood of RA patients were also found to migrate along TNF concentration gradients ex vivo. Accordingly, blockade of either TNF or TNFRI nearly abrogated in vitro T cell migration in synovial tissue. CONCLUSION: Our findings indicate that the interaction of TNF with TNFRI is pivotal for T cell migration in synovial tissue in vitro, and thereby suggest a relevant role of the cytokine for in vivo T cell trafficking to synovitic joints.

Experimental evidence of impingement induced strains at the interface and the periphery of an embedded acetabular cup implant.

After total hip arthroplasty, impingement of implant components may occur during every-day patient activities causing increased shear stresses at the acetabular implant-bone interface. In the literature, impingement related lever-out moments were noted for a number of acetabular components. But there is little information about pelvic load transfer. The aim of the current study was to measure the three-dimensional strain distribution at the macrostructured hemispherical interface and in the periphery of a standard acetabular press-fit cup in an experimental implant-bone substitute model. An experimental setup was developed to simulate impingement loading via a lever arm representing the femoral component and the lower limb. In one experimental setup 12 strain gauges were embedded at predefined positions in the periphery of the acetabular cup implant inside a tray, using polyurethane composite resin as a bone substitute material. By incremental rotation of the implant tray in steps of 10 and 30 deg, respectively, the strains were measured at evenly distributed positions. With the described method 288 genuine strain values were measured in the periphery of an embedded acetabular cup implant in one experimental setup. In two additional setups the strains were evaluated at different distances from the implant interface. Both in radial and meridional interface directions strain magnitudes reach their peak near the rim of the cup below the impingement site. Values of equatorial strains vary near zero and reach their peaks near the rim of the cup on either side and in some distance from the impingement site. Interestingly, the maximum of averaged radial strains does not occur, as expected, close to the interface but at an interface offset of 5.6 mm. With the described experimental setup it is now possible to measure and display the three-dimensional strain distribution in the interface and the periphery of an embedded acetabular cup implant. The current study provides the first experimental proof of the high local stresses gradients in the direct vicinity of the impingement site. The results of the current study help for a better understanding of the impingement mechanism and its impact on acetabular cup stability.

Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis by laser scanning cytometry.

INTRODUCTION: Suitable biomarkers are essential for therapeutic strategies in personalized medicine in terms of diagnosis as well as of prognosis. With highly specific biomarkers, it is possible, for example, to identify patients with poor prognosis, which enables early intervention and intensive treatment. The aim of this study was to identify and validate biomarkers and possible combinations for a prospective use in immunoscintigraphy, which may improve diagnosis of rheumatoid arthritis (RA) patients with consideration of inflammatory activity in the affected joints. Therefore, we tested several monoclonal antibodies (mAbs) directed against cellular-surface molecules on cells likely to be involved in the pathogenesis of RA. METHODS: Synovial tissue from patients with long-standing RA (accompanied by synovitis with varying states of current activity) and patients with acute non-RA arthritis were stained for surface molecules on different cell types by using fluorochrome-labeled antibodies. Tissue analysis was done by laser scanning cytometry (LSC), and statistical evaluation, by discriminant analysis and ROC analysis. RESULTS: CD11b, HLA-DR, CD90, and CD64 revealed significant differences between tissues from patients with RA and acute non-RA arthritis. Especially with the expression of CD64, both patient cohorts could be discriminated with high sensitivity and specificity. RA classification was improved by simultaneously investigating the expression of two or three different surface proteins, such as HLA-DR, CD90, and CD29 in the tissue. The simultaneous analysis of CD64 together with CD304 or the combination of CD11b and CD38 was suitable for the identification of RA patients with high current activity in synovitis. CONCLUSIONS: In this study, we showed that LSC is a novel reliable method in biomarker prevalidation in RA. Hence, identified mAbs in situ may allow their potential use in in vivo approaches. Moreover, we proved that biomarker-combination analysis resulted in better discrimination than did single-marker analysis. Combinations of these markers make a novel and reliable panel for the discrimination between RA and acute non-RA arthritis. In addition, further expedient combinations may be novel promising biomarker panels to identify current activity in synovitis in RA.

Combined multi-body and finite element investigation of the effect of the seat height on acetabular implant stability during the activity of getting up.

An important question in assessing the stability of a total hip arthroplasty is the effect of daily physical activities of patients. The aim of this study is to examine these effects when standing up from three different seat heights. A musculoskeletal body model has been modified to simulate the three different seat heights. The calculated muscle forces have been transferred to a finite element model of a pelvis. The pelvis model was created from a hemipelvis CT dataset. As an implant component, a metal socket with a polyethylene insert was used. A primary implantation situation was modelled. For the analysed patient activities the highest hip contact forces and the highest micromotions occur at the beginning of the motion. The results of this study show that standing up from a certain seat height can have a significant influence on the micromotions in the implant-bone interface.

Association of anticytomegalovirus seropositivity with more severe joint destruction and more frequent joint surgery in rheumatoid arthritis.

OBJECTIVE: Expansion of autoreactive CD4+CD28(null) T cells is associated with extraarticular disease manifestations, including rheumatoid vasculitis, and it has recently been demonstrated that expansion of these T cells is associated with anticytomegalovirus (anti-CMV) seropositivity. This study was undertaken to investigate a possible link between latent CMV infection and rheumatoid arthritis (RA). METHODS: In a retrospective analysis, anti-CMV antibodies and clinical, serologic, and radiologic parameters of joint destruction were examined in 202 RA patients and 272 healthy controls. In addition, frequencies of CD4+CD28(null) T cells; concentrations of the cytokines monocyte chemotactic protein 1 (MCP-1), interferon-α (IFNα), and IFN-inducible protein 10; and anti-CMV-specific T cell responses were analyzed in RA patients. RESULTS: Overall, no significant difference in the frequency of anti-CMV seropositivity between RA patients and healthy controls was observed. Among individuals older than age 55 years, however, anti-CMV IgG antibodies were significantly more frequent in RA patients than controls (65.3% and 54.7%, respectively; P = 0.05). Anti-CMV seropositivity in RA patients was associated with an increased frequency of CD4+CD28(null) T cells and increased serum concentrations of MCP-1. The frequency of anti-CMV-specific CD4+ T cells producing IFNγ was increased in RA patients compared to controls. Most importantly, anti-CMV-seropositive RA patients showed radiographic evidence of more advanced joint destruction and had increased frequencies of joint-related surgical procedures, indicating more severe joint disease. CONCLUSION: Our findings indicate that latent CMV infection aggravates the clinical course of RA and is associated with increased frequencies of CD4+CD28(null) T cells and of CMV-specific IFNγ-secreting CD4+ T cells.

Accuracy and reliability of different methods to evaluate the acetabular cup version from plain radiographs.

PURPOSE: The purpose of this study was to compare different methods of evaluating the version of a metallic acetabular cup from plain radiographs and to compare them regarding their accuracy, inter- and intra-observer reliability. METHODS: Conventional anterior-posterior radiographs were taken of a phantom-model at different defined ante- and retroversion angles of the acetabular cup. The version angles of the acetabular cup were derived according to four different established methods from the radiographs by five independent examiners. RESULTS: We were able to determine the radiographic version with the greatest accuracy according to a modified technique of Pettersson et al. Furthermore, we found the highest intra- and inter-observer reliability using this technique. CONCLUSIONS: A modified technique of Pettersson et al. broadens the spectrum of applicability for the radiographic evaluation of the version angle of metal-backed acetabular cups in comparison to the originally introduced method. In clinical practice, however, the significance of deriving the cup position from standard radiographs should not be over-estimated and therefore a computed tomography should be performed in certain critical cases.

Finite element analysis of shear stresses at the implant-bone interface of an acetabular press-fit cup during impingement.

After total hip replacement (THR) impingement of the implant components causes shear stresses at the acetabular implant-bone interface. In the current study the finite element method (FEM) was applied to analyse the shear stresses at a fully bonded implant-bone interface assuming total ingrowth of the cup. The FE model of a press-fit acetabular component and the proximal part of the femoral component incorporates non-linear material and large sliding contact. The model was loaded with a superior-medial joint load of 435 N simulating a two-legged stance. Starting at initial impingement, the femoral component was medially rotated by 20 degrees . The peak tilting shear stress of -2.6 MPa at the impingement site takes effect towards the pole of the cup. The torsional shear stress at the impingement site is zero. On each side of the impingement site, there are extrema of torsional shear stress reaching -1.8 and 1.8 MPa, respectively. The global peak shear stress during impingement may indicate a possible starting point for cup loosening. The pattern of the torsional shear stresses suggests that besides the symmetric lever-out, an additional asymmetrical tilting of the cup occurs that can be explained by the orientation of the applied joint load.

The contact-mediated response of peripheral-blood monocytes to preactivated T cells is suppressed by serum factors in rheumatoid arthritis.

Stimulation of monocytes/macrophages after cell contact with preactivated T cells has been suggested to contribute to the excessive TNF-alpha production in rheumatoid arthritis (RA). In this study, T cell-contact-dependent TNF-alpha production by peripheral-blood monocytes in vitro was investigated and found to be significantly lower in treated and untreated patients with RA than in healthy controls. This suppression was not due to a general deficiency of monocytes to respond, because responses to lipopolysaccharide were comparable in patients and controls. In agreement with the pivotal role of TNF-alpha in RA, T cell-dependent induction of TNF-alpha in synovial macrophages was fivefold to tenfold higher than in peripheral-blood monocytes from either patients or controls. The decreased response of peripheral-blood monocytes from patients with RA was found to be mediated by inhibitory serum factors, because the addition of patient sera to monocytes from healthy controls suppressed TNF-alpha response in the co-culture assay. Preincubation of monocytes from healthy controls with RA serum was sufficient to suppress the subsequent TNF-alpha response in T cell co-cultures, indicating that inhibitory factors do indeed bind to monocyte surfaces, which might represent a regulatory counter-action of the immune system to the long-standing and consuming autoimmune process in RA. There are some indications that apolipoprotein A-1 might be part of this regulatory system.