Synovial-like Interface Membrane Research Articles

Unexpected positive cultures in patients with arthrofibrosis following total hip and total knee arthroplasty.

It has been suggested that low-grade infections could be the cause of arthrofibrosis. However, this hypothesis has not been conclusively proven. The aim of this study is to assess the incidence of unexpected positive cultures (UPC) in patients undergoing revision total joint arthroplasty for a diagnosis of arthrofibrosis. A retrospective single-centre review was performed. All patients who underwent an aseptic revision due to histologically confirmed arthrofibrosis (based on the synovial-like interface membrane (SLIM) criteria) were included. The incidence of UPC was then calculated. A total of 147 patients were included. Of these, 100 underwent a total knee arthroplasty (TKA) procedure and 46 a total hip arthroplasty (THA) surgery. One patient had a periprosthetic joint infection and was therefore excluded. Of the 146 included patients, 6 had confirmed UPC (4.08%). The following bacteria were identified: Anaerococcus octavius, Staphylococcus epidermidis, Enterobacter cloacae, Staphylococcus hominis, Streptococcus pluranimalium, Staphylococcus pettenkoferi. Our results suggest that the incidence of UPC in patients with arthrofibrosis is low. It is lower than that of UPC in patients that undergo a revision for other causes. There is no proven relationship between histologically confirmed arthrofibrosis following total joint arthroplasty and prosthetic joint infection.

Particle disease and its effects on periarticular tissue

Particle disease is the condition caused by wear debris on surrounding tissues and influences the well-being of arthroplasty patients. This condition is multifactorial due to the type of bearing couple, head size and implant position. Subsequent periprosthetic osteolysis and soft tissue reactions, can lead to revision THA surgery. The periprosthetic synovial membrane (synovial-like interface membrane, SLIM) is used in diagnostics when the cause of implant failure is uncertain. Detailed analysis of synovial fluid and bone marrow could improve the diagnostic procedure and strengthen the cases for revision surgery and the underlying biology. Alarge number of research approaches on this topic have evolved and continue to be utilized in the clinic.

Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue

BackgroundThe identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination.MethodsThe cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles.ResultsAll implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis.ConclusionsThe HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies.

Supramacroparticulate PE in 6 different joint endoprostheses localisations: An indicator for PE damage?

In the histopathological particle algorithm polyethylene (PE) particles with maximum lengths of more than 100μm – called PE supramacroparticles – are identified exclusively for knee joint and hip prostheses. However, a definitive characterisation, detection in all joint localisations and a causal clarification of the pathogenesis are lacking. In this study a total of 175 SLIM (synovial-like interface membrane) cases with PE supramacroparticles of knee joint prostheses (n=89), hip joint prostheses (n=44), ankle joint prostheses (n=36) and prostheses in three localisations of the upper extremities (n=6) were systematically investigated. The arithmetic mean of the particle length varied greatly within the prosthesis types. This had a significant positive correlation with the prosthesis lifetime and negative correlation with the date of implantation. It can be concluded that both the lifetime and the time of implantation have an influence on the particle length. The prostheses with supramacroparticulate damage moreover showed a clearly reduced survival rate compared with other data published on the prosthesis lifetime. The material wear therefore could not be attributed solely to the usual fatigue factors. Since loosening of the prostheses, decentring of the PE components or damage to the PE inlay existed in all cases, mechanical dysloading seems to be the most probable cause of PE supramacroparticle genesis. Due to the striking length and for demarcation from PE macroparticles, the term supramacroparticulate PE is proposed for a length of more than 100μm. In the extended histopathological particle algorithm supramacroparticulate PE has been included in the macroparticles category and should be taken into account and interpreted causally in histopathological diagnostics of joint prosthesis failure.

CD15 focus score: Infection diagnosis and stratification into low-virulence and high-virulence microbial pathogens in periprosthetic joint infection

IntroductionThe aim of the work was to validate the CD15 focus score for the infection pathology of periprosthetic joint infection in a large group and to clarify whether a stratification into low-virulence and high-virulence microbial pathogens is possible by means of the CD15 focus score (quantification of CD15 positive granulocytes). MethodsThe histopathology of 275 synovial tissue samples taken intraoperatively during revision operations (n=127 hip, n=141 knee, n=2 shoulder, n=5 ankle) was evaluated according to the SLIM consensus classification (SLIM=synovial-like interface membrane). Neutrophilic granulocytes (NG) were quantified by the CD15 focus score on the basis of the principle of focal maximum infiltration (focus) with evaluation of one field of vision (about 0.3mm2). The quantification values were compared with the microbiological diagnoses taking into consideration the virulence groups of low-virulence and high-virulence microbial pathogens and mixed infection. ResultsThe patients with positive microbiological findings (n=160) had significantly (p<0.001, Mann-Whitney U test) higher CD15 focus score values than patients with negative microbiological findings (n=115), the cut-off value being 39 cells per high power field (HPF). The CD15 focus score values of low-virulence microbial pathogens (n=94) were significantly lower (p<0.001, Mann-Whitney U test) than the values of high-virulence microbial pathogens (n=55), the cut-off value being 106 cells per HPF. Based on the microbiological diagnosis the sensitivity with respect to a microbial infection is 0.91, the specificity 0.92 (PPV=0.94; NPV=0.88; accuracy: 0.92; AUC=0.95). Based on the differentiation of the CD15 focus score values between low-virulence and high-virulence microbes the sensitivity is 0.70 and the specificity 0.77 (PPV=0.63; NPV=0.81; accuracy=0.74; AUC=0.74). ConclusionAs a result of the high sensitivity and specificity, the easy to use CD15 focus score is a diagnostically valid score for microbial periprosthetic infection. A differentiation between low-virulence and high-virulence microorganism of sufficiently high diagnostic quality is additionally possible as a result of the defined quantification of CD15 positive granulocytes (the CD15 focus score) histopathological diagnosis of microbial infections is possible, which on the one hand supports the microbiological diagnosis and on the other hand by the stratification into low-virulence and high-virulence microbial pathogens could represent an additional basis for a pathogen-specific antibiotic treatment in the event of unclear constellations of findings.

A new algorithm for histopathological diagnosis of periprosthetic infection using CD15 focus score and computer program CD15 Quantifier

Introduction. A simple microscopic diagnostic quantification system for neutrophile granulocytes (NG) was developed evaluating a single focal point (CD15 focus score) which enables the detection of bacterial infection in SLIM (synoviallike interface membrane) Additionally a diagnostic algorithm is proposed how to use the CD15 focus score and the quantification software (CD15 Quantifier). Methods. 91 SLIM removed during revision surgery for histopathological diagnosis (hip; n=59 and knee; n=32) underwent histopathological classification according to the SLIM-consensus classification. NG where identified immunohistochemically by means of a CD15-specific monoclonal antibody exhibiting an intense granular cytoplasmic staining pattern. This pattern is different from CD15 expression in macrophages showing a pale and homogenous expression in mononuclear cells. The quantitative evaluation of CD15-positive neutrophils granulocytes (CD15NG) used the principle of maximum focal infiltration (focus) together with an assessment of a single focal point (approximately 0.3 mm2). This immunohistochemical data made it possible to develop CD15 Quantifier software which automatically quantifies CD15NG. Results. SLIM-cases with positive microbiological diagnosis (n=47) have significantly (p

Revision arthroplasty : Histopathological diagnostics in periprosthetic joint infections

Histopathological differences in synovia and synovial-like interface membrane (SLIM) patterns can be used to differentiate periprosthetic particle-induced reactions, bacterial infections (bacterial synovitis and osteomyelitis), mechanical-induced tissue alterations, adverse reactions to implant material, and arthrofibrosis (SLIM consensus classification). Because of differences in treatment the diagnosis of a bacterial implant infection is very important. Histopathological tests and scoring systems are important diagnostic tools in identifying deep implant infections in patients with unclear clinical history as well as radiographic and laboratory studies. Modern enzyme PCR-based methods, histochemical- and immune-histopathological techniques (CD3,CD15, CD68) are useful in identifying specific and nonspecific infections, as well as differentiating postsurgical changes from recurrent infections in patients with a spacer. In all histopathological scoring systems for bacterial infection, quantifying the number of neutrophil granulocytes in a defined number of high power fields is crucial. Neutrophil granulocytes can be detected through histochemical methods and more specifically by immune-histopathological techniques and by various quantification systems (histopathological scores) leading to the diagnosis of bacterial peri-implant infection. One important function of histopathology, apart from diagnosing infection, is to rule out other mechanisms of implant failure, such as tumor infiltrations, particle-induced reactions, and adverse reactions to implant materials.

IMPLANT-ASSOCIATED PATHOLOGY: AN ALGORITHM FOR IDENTIFYING PARTICLES IN HISTOPATHOLOGIC SYNOVIALIS/SLIM DIAGNOSTICS

In histopathologic SLIM diagnostic (synovial-like interface membrane, SLIM) apart from diagnosing periprosthetic infection particle identification has an important role to play. The differences in particle pathogenesis and variability of materials in endoprosthetics explain the particle heterogeneity that hampers the diagnostic identification of particles. For this reason, a histopathological particle algorithm has been developed. With minimal methodical complexity this histopathological particle algorithm offers a guide to prosthesis material-particle identification. Light microscopic-morphological as well as enzyme-histochemical characteristics and polarization-optical proporties have set and particles are defined by size (microparticles, macroparticles and supra- macroparticles) and definitely characterized in accordance with a dichotomous principle. Based on these criteria, identification and validation of the particles was carried out in 120 joint endoprosthesis pathological cases. A histopathological particle score (HPS) is proposed that summarizes the most important information for the orthopedist, material scientist and histopathologist concerning particle identification in the SLIM.

Update on endoprosthesis pathology: Particle algorithm for particle identification in the SLIM

When it comes to endoprosthesis pathologies, for example, implant-allergic/toxic problems, as a cause of implant failure, particle identification has an important role to play in the histopathological diagnostics of the neosynovial/periprosthetic membrane (synovial-like interface membrane, SLIM). The variability of materials in endoprosthetics and differences in particle pathogenesis explain the particle heterogeneity that hampers the diagnostic identification of particles. For this reason, a histopathological particle algorithm has been developed that, with minimal methodical complexity, offers a guide to particle identification. Light microscopic–morphological as well as enzyme–histochemical characteristics and polarization–optical properties have been defined. Particles are characterized in accordance with a dichotomous principle. Based on these criteria, identification and validation of the particles was carried out in 105 joint endoprosthesis pathological cases. A particle score is proposed that summarizes the most important information for the orthopedist.

Histopathologische Differenzialdiagnostik bei gelenkimplantatallergischen Fragestellungen

Total joint replacement has greatly increased over the last decades and so have endoprothesis-associated pathologies. European studies have shown a 10-year durability varying from 88% to 95%. By means of histopathology different pathogenetic synovial-like interface membrane (SLIM) patterns that lead to reduction of implant durability can be discerned, such as periprosthetic particles, bacterial infections and arthrofibrosis. Subsequently, SLIM types have been determined in a revised consensus classification including particle-induced type (type I) so-called non-septic loosening, infection type (type II) so-called septic loosening, combination type (type III) of bacterial and particle-induced types, indifferent type with mechanical and functional disorders (type IV), osseus pathologies (type V), arthrofibrotic type (type VI, endoprosthesis-associated arthrofibrosis) and allergic/immunological/toxic reactions to prosthesis material (type VII). Particles are characterized histopathologically according to the Krenn particle algorithm. In cases of severe lymphocyte/macrophage infiltration, necrosis, abrasion particle detection and granuloma formation, a toxic or allergic reaction to implant material should be considered. As a direct abrasion particle-induced toxicity cannot be differentiated from a particle-induced allergic type VII reaction to implant material, the histopathological diagnosis of toxic reaction to implant material or allergic reaction to implant material should be made with caution and only in association with immunological, allergic and clinical data. It is recommended that tissue samples should be arthroscopically taken from different regions: close to the prosthesis, distant from the prosthesis and from bone tissue. The pathologist should be given information concerning clinical, allergological and microbiological data.

Erweiterte Konsensusklassifikation

The revised classification of the periprosthetic membrane (synovial-like interface membrane SLIM) encompasses all pathological alterations which can occur as a result of endoprosthetic replacement of major joints and lead to a reduction in durability of prostheses. This also includes the established consensus classification of SLIM by which aseptic and septic prosthetic loosening can be subdivided into four histological types and histopathological criteria for additional pathologies: endoprosthesis-associated arthrofibrosis, immunological/allergic alterations and osseous pathologies. This revision represents the foundation for the histopathological diagnostics of the total spectrum of diseases associated with joint prostheses, is a suitable basis for a standardized diagnostic procedure and etiological clarification of endoprosthesis failure and also as a data standard for endprosthesis registers, in particular for registers based on routine data (e.g. German endoprosthesis register).

Seppo Santavirta: The Life and Work of an Orthopaedic Surgeon and Scientist. A Tribute From His Friends

Seppo Santavirta: The Life and Work of an Orthopaedic Surgeon and Scientist. A Tribute From His Friends

Inflammatory reactions in the wear particle induced and infectious periprosthetic membrane of loosened hip- and knee endoprostheses: pathogenetic relevance of differentially expressed genes cd9, cd11b, cd18, cd52 and pdgfr?

A previous cDNA-microarray analysis described constantly differentially expressed genes in wear particle induced and infectious SLIM (synovial-like interface membrane). This study aims to validate the cDNA microarray data in order to approve differences of the gene expression profiles of RNA and proteins. Tissue from 16 wear particle induced and 20 infectious periprosthetic membranes were analyzed by RT-PCR and immunohistology with regard to the expression of inflammatoric associated genes. RT-PCR showed the genes cd9, cd11b, cd18, cd52 as well as pdgfrbeta in interface membranes. In the wear particle induced membrane the immunohistochemical analysis showed a significantly weaker gene expression of PDGFRbeta, whereas the differential overexpression of CD9, CD11b and CD52 was confirmed. For CD18, there was no difference in expression between wear induced and infectious periprosthetic tissue. Different pathomechanisms, which are reflected by different gene expression profiles, might produce different types of periprosthetic membranes. By RT-PCR and immunohistochemical analysis the micro array data of the genes cd9, cd11b, cd52 and pdgfrbeta could be validated. Identifying the gene products of cd9, cd11b and cd52 in blood or tissue may help to differentiate between wear induced and infectious loosening.

Development and characteristics of a synovial‐like interface membrane around cemented tibial hemiarthroplasties in a novel rat model of aseptic prosthesis loosening

Objective Aseptic prosthesis loosening (APL) is related to the formation and aggressive growth of a synovial-like interface membrane (SLIM) between prosthesis and bone. However, investigation of the early phases of SLIM development in humans presents major difficulties. This study was undertaken to develop and characterize the usefulness of a novel animal model of APL that is based on an established model of defined exercise in a running wheel by Wistar rats that have been subjected to intracranial self-stimulation (ICSS). Methods Cemented tibial hemiarthroplasties were implanted into the left knees of 7 male Wistar rats. After 2 weeks, exercise in a running wheel was started in all rats, with a running-load of 2 hours/day for 5 days/week. Six months postoperatively, the knee joints were removed, decalcified, and embedded in paraffin. Histologic evaluation on hematoxylin and eosin–stained sections was performed to investigate the development of a SLIM and the presence of cement debris particles. To characterize the SLIM on a molecular level and investigate growth-regulating factors, the expression of transforming growth factor β (TGFβ) and the antiapoptotic molecule Bcl-2 was analyzed by immunohistochemistry. Results Although the prostheses appeared mechanically stable after 6 months, the development of SLIM with areas of bone resorption was seen in all samples. Resembling human SLIM, these membranes consisted of loose fibrous tissue, with cement debris particles located particularly at sites originally attached to the prostheses. Immunohistochemistry studies revealed the expression of TGFβ and Bcl-2 in all specimens. Interestingly, staining for TGFβ and Bcl-2 was restricted to areas where the SLIM were attached to bone. In contrast, there was only negligible expression of both proteins at sites adjacent to the prostheses. Conclusion Our findings demonstrate that the ICSS Wistar rat model constitutes a feasible tool for studying early stages of APL, and specifically the effect of defined running exercise on SLIM formation. The results further suggest that both cellular proliferation, as stimulated by TGFβ, and altered apoptosis contribute to early stages of SLIM formation. The expression patterns of TGFβ and Bcl-2 indicate that the growth of the SLIM is initiated and promoted from the bone rather than from the prosthesis.

Development and characteristics of a synovial-like interface membrane around cemented tibial hemiarthroplasties in a novel rat model of aseptic prosthesis loosening.

Aseptic prosthesis loosening (APL) is related to the formation and aggressive growth of a synovial-like interface membrane (SLIM) between prosthesis and bone. However, investigation of the early phases of SLIM development in humans presents major difficulties. This study was undertaken to develop and characterize the usefulness of a novel animal model of APL that is based on an established model of defined exercise in a running wheel by Wistar rats that have been subjected to intracranial self-stimulation (ICSS). Cemented tibial hemiarthroplasties were implanted into the left knees of 7 male Wistar rats. After 2 weeks, exercise in a running wheel was started in all rats, with a running-load of 2 hours/day for 5 days/week. Six months postoperatively, the knee joints were removed, decalcified, and embedded in paraffin. Histologic evaluation on hematoxylin and eosin-stained sections was performed to investigate the development of a SLIM and the presence of cement debris particles. To characterize the SLIM on a molecular level and investigate growth-regulating factors, the expression of transforming growth factor beta (TGFbeta) and the anti-apoptotic molecule Bcl-2 was analyzed by immunohistochemistry. Although the prostheses appeared mechanically stable after 6 months, the development of SLIM with areas of bone resorption was seen in all samples. Resembling human SLIM, these membranes consisted of loose fibrous tissue, with cement debris particles located particularly at sites originally attached to the prostheses. Immunohistochemistry studies revealed the expression of TGFbeta and Bcl-2 in all specimens. Interestingly, staining for TGFbeta and Bcl-2 was restricted to areas where the SLIM were attached to bone. In contrast, there was only negligible expression of both proteins at sites adjacent to the prostheses. Our findings demonstrate that the ICSS Wistar rat model constitutes a feasible tool for studying early stages of APL, and specifically the effect of defined running exercise on SLIM formation. The results further suggest that both cellular proliferation, as stimulated by TGFbeta, and altered apoptosis contribute to early stages of SLIM formation. The expression patterns of TGFbeta and Bcl-2 indicate that the growth of the SLIM is initiated and promoted from the bone rather than from the prosthesis.

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Increased interleukin-8 (IL-8) expression is related to aseptic loosening of total hip replacement.

Aseptic loosening is an increasing problem in total hip replacement (THR). Chronic inflammatory reaction against implant wear particle results in collageno- and osteolysis, leading to loosening of the implant. Cytokines are known to play a major role in this particular inflammatory process. The aim of the present study was to examine interleukin-8 (IL-8) in the synovial-like interface membrane (SLIM) and pseudocapsular tissue of THRs and to compare it to normal knee synovial membrane. Eleven patients suffering from aseptically loosened THRs were included. All the SLIM and pseudocapsular tissue samples were obtained during revision operations. Ten control samples of normal synovium were collected per arthroscopy from the superior recessus of the knee. For immunohistochemical IL-8 detection, polyclonal mouse anti-human immunoglobulin (Ig)G1 IL-8-primary antibody was used with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. Results were quantitated using the Vidas image analysis system. The highest count levels (mean +/- SEM) were detected in SLIM tissue (386+/-82 cells/mm2). The difference was statistically significant compared with pseudocapsular tissue (193+/-36 cells/mm2) and control samples (18+/-5 cells/mm2). Count levels in control tissue were on average 5% of the SLIM tissues values. The present study determines for the first time the cellular origin of IL-8 in aseptically loosened THRs and also quantitates the IL-8-producing cells in the periprosthetic tissue. The results reveal a high rise in IL-8 concentration in SLIM and in synovial tissues. This finding moves us one step forward in solving the complex network of multiple factors affecting loosening of hip implants.