A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

[Localized tenosynovial giant cell tumor : Results from the Histopathological Arthritis Register of the German Society for Orthopedic Rheumatology]. / Der lokalisierte tenosynoviale Riesenzelltumor (L-TSRZT) : Ergebnisse aus dem histopathologischen Arthritisregister der Deutschen Gesellschaft für Orthopädische Rheumatologie.

BACKGROUND: The tenosynovial giant cell tumor (pigmented villonodular synovitis) is a proliferative, mainly benign soft tissue tumor of the tendon sheaths, bursae and joints arising from the synovia. It can be divided into circumscribed localized and destructive diffuse types. Approximately 1% of all joint diseases are due to this entity. The tumor is considered as a rarity. Mostly case studies exist. For this study the focus was set on the localized type (L-TSRZT), which accounts for 90% of the diagnoses of this tumor. Given its rarity, data are limited. Therefore, the research aim was to provide data on prevalence, primary location and sensitivity of clinical versus histopathological diagnosis in a German sample. METHODS: Based on the Histopathological Arthritis Register of the German Society for Orthopedic Rheumatology, the data of the L­TSRZT were retrospectively analyzed (time frame 1 January 2018-28 December 2020). RESULTS: This database contained N = 7595 cases of arthropathy. A total of n = 45 patients with the diagnosis L­TSRZT were identified. The prevalence of the tumor was 0.6%, 95% CI [0.4%, 0.8%], or 5.9 cases per 1000. The primary location involved the finger (48.9%). In 14 of 45 cases the diagnosis was correctly determined from the clinical side, corresponding to a sensitivity of 31.1%, 95% CI [18.2%, 46.7%]. CONCLUSION: For the first time, this paper was able to provide data on a large sample for Germany. Notably, the low sensitivity of the clinical diagnosis confirms the importance of histopathology for diagnosing L­TSRZT.

[Histopathological diagnostics of arthrofibrosis]. / Histopathologische Diagnostik der Arthrofibrose.

Joint surgery is one of the most important and successful disciplines in surgery; nevertheless, complications still occur, especially in total knee arthroplasty and surgery of the anterior cruciate ligament. A significant disease in this context is arthrofibrosis. This review article presents the cellular and molecular pathogenetic concept of arthrofibrosis, the spectrum of histopathological diagnostics and differential diagnostics and a classification into joint endoprosthesis-associated and non-joint endoprosthesis-associated arthrofibrosis is proposed. The basis of the histopathological diagnostics is the standardized tissue removal with subsequent fixation in formalin. In the case of joint implant failure and the problem of endoprosthesis-associated arthrofibrosis, the histopathological diagnostics can be carried out according to the consensus classification of synovia-like interface membrane (SLIM). Arthrofibrosis is characterized by fibrosis, a high fibroblast cellularity with immunohistochemical detection of cytoplasmic beta catenin expression. The presence of endoprosthesis-associated arthrofibrosis is probable above a threshold of 20 beta catenin positive fibroblasts per high-power field (HPF). The diagnosis of a non-endoprosthesis-associated arthrofibrosis can be classified according to the joint pathology algorithm. Diffuse non-endoprosthesis-associated arthrofibrosis is characterized by generalized proliferation of connective tissue in the whole joint and localized circumscribed arthrofibrosis is characterized by a nodose cyclops-like fibrosis. The clarification of the cause of arthrofibrosis is based on an interdisciplinary cooperation. In addition to the histopathological diagnostics, this includes clinical, surgical, biomechanical, arthroscopic, microbiological, laboratory parameter and radiological findings.

Diagnostic value of the CD 15 focus score in two-stage revision arthroplasty of periprosthetic joint infections : High specificity in diagnosing infect eradication.

INTRODUCTION: The purpose of this study is to use the CD15 focus score (FS) to determine the sensitivity and specificity of bacterial infection persistence in spacer-based two-stage revision arthroplasty. METHODS: The analysis comprises 112 cases that were subjected to revision due to the presence of infection upon replacement of a joint endoprosthesis. The histopathological data were collected in accordance with the synovial-like interface membrane (SLIM) classification and the CD15-FS and correlated with the microbiological data (MD). The quantifying evaluation of the CD15-FS was performed without knowledge regarding the microbiological data (MD). Correlation with the MD was performed after a 14-day cultivation period. RESULTS: With a single evaluation (1 focus, field area: 1.2 mm2) with a score value of 42, the CD15-FS showed a sensitivity for the eradication of infections of 0.64 and a specificity of 0.79 (PPV = 0.5; NPV = 0.87). With tenfold evaluation (10 foci, field area: 12 mm2) with a score value of 220, the sensitivity for the eradication was 0.68, the specificity 0.91 (PPV = 0.7; NPV = 0.89). No statistically significant correlation between the score values and the different infectious species could be detected. Based on the MD in 112 cases the rate of infection eradication was 75%. Polymethylmethacrylate-particles (PMMA) were detected in the perispacertissue in 64 cases (58%). No significant correlation could be established between microbiological pathogen detection and the presence of PMMA. CONCLUSION: In all cases (n = 112), periimplant synovial tissue (SLIM) with variable fibroblastic cellularity, capillary proliferation, leukocytic infiltration, fibrin deposition, new formation of woven bone and detection of PMMA particles was observed. These cases were classified as type IX perispacer synovialis/SLIM: type IX­A with histopathological infection eradication and type IX­B with histopathological infection persistence.

[Joint tumors: rare but important differential diagnoses of malignant and benign tumors as well as pseudotumors in rheumatology]. / Gelenktumoren: Seltene, aber wichtige Differenzialdiagnosen von malignen und benignen Tumoren sowie Pseudotumoren in der Rheumatologie.

This review article elucidates the differential diagnostics of malignant and benign joint tumors, pseudotumors of the joints and the peri-implant tissue, which are rare but important entities in rheumatology and orthopedic rheumatology. The tissue of origin includes the synovium, peri-implant tissue, peri-articular fibrous tissue and peri-articular osseous tissue. Pseudotumors can be viewed as independent but heterogeneous entities. These are essentially manifested as tumor-like depositions of crystals, calcareous deposits, vascular malformations, ectasia of the synovia and joint capsule tissue and pseudocysts. Other causes for pseudotumors are focal destructive inflammation (e.g. induced by foreign bodies), high grade synovitis and focal fibrinoid necrosis (i.e. rheumatoid nodules). Methodologically, these diagnostics are based on conventional standard staining methods, immunohistochemical analyses of formalin-fixed and paraffin-embedded materials and on molecular diagnostic procedures. The latter are of great importance in cases of benign and malignant joint tumors. The most important immunohistochemical markers with respect to joint tumors are S100, SM-actin, CD68, CD34, STAT6, clusterin, Muc­4, beta-catenin and MDM2-FISH. The following markers are recommended for the differential diagnostics and typing of periarticular tumor metastases in the pathology of rheumatic diseases: AE1/AE3, CK8, p63, TTF­1, TGB, PSA, androgen receptor, GATA, CD56, chromogranin, CDX­2, SAT-B2, SALL4, estrogen and progesterone receptors, CD45LCA, CD30, CD79a and S100. Necrosis, inflammatory infiltrations and reparative inflammatory changes may complicate the histopathological classification. Therefore, a correlation with clinical, microbiological and radiological data in the sense of interdisciplinary synergistic diagnostics may be required.

Dental Apical Inflammation Score (DAIS): Histopathological scoring for the evaluation of the apical inflammatory activity and local bone destruction.

OBJECTIVE: The purpose of this study was to evaluate 210 periapical lesions with a newly created Dental Apical Inflammation Score/DAIS with regard to their inflammatory cell infiltration, bone tissue, epithelium, bacteria and foreign material. STUDY DESIGN: Specimens were obtained from 51 different dental practices over a period of 11 months. These specimens were then sent in for histopathological routine diagnostics. RESULTS: The DAIS classified 81 cases of Type 1 (acute inflammation = low, chronic inflammation = low), 79 cases of Type 2 (acute inflammation = low, chronic inflammation = high), 46 cases of Type 3 (acute inflammation = high, chronic inflammation = low) and 4 cases of Type 4 (acute inflammation = high, chronic inflammation = high). Bone tissue was found in 141 cases, signs for bacterial osteitis in 49 cases, cyst epithelium in 40 cases and foreign material in 27 cases. In 210 cases, cyst epithelium was evident in 27.2 % of Type 1, 15.2 % of Type 2, 8.7 % of Type 3 and in 50 % of Type 4 (p = .019). The 141 cases containing bone tissue showed signs of bacterial osteitis in 16.1 % of Type 1, 29.8 % of Type 2, 77.8 % of Type 3 and in 100 % of Type 4 (p < .001). In 64 cases, Bacteria was evident in 30 % of Type 1, 25 % of Type 2, 55 % of Type 3 and in 100 % of Type 4 (p = .013). CONCLUSION: The DAIS could classify apical lesions with statistically significant differences. Bacterial osteitis in apical lesions was reported for the first time.

Heterotopic Ossification in Orthopaedic and Trauma surgery: A Histopathological Ossification Score.

Heterotopic Ossification (HO) is a potential long-term complication in orthopaedic surgery. It is commonly classified according to the Brooker classification, which is based on radiological findings. To our knowledge the correlation of histological features to the Brooker grade is unknown as is the association between HO and the indication for revision. The aim of this paper is to analyze the ossification grade of HO tissue in patients undergoing revision hip and knee arthroplasty and to propose a histologically based classification system for HO. We also assess the relationship between the grade of HO and the indication for revision (septic and aseptic revision). From January to May 2019 we collected 50 human HO samples from hip and knee revision arthroplasty cases. These tissue samples were double-blinded and sent for histopathological diagnostic. Based on these results, we developed a classification system for the progression of HO. The grade of ossification was based on three characteristics: Grade of heterotopic ossification (Grade 1-3), presence of necrosis (N0 or N1) and the presence of osteomyelitis (HOES-Score Type 1 to 5). Demographic data as well as surgical details and indication for surgery was prospectively collected from clinical records. Fifty tissue samples were harvested from 44 hips and 6 knee joints. Of these 33 exhibited Grade I ossifications (66%), followed by 11 Grade II (22%) and one Grade III (2%). Necrosis was noted in two tissue samples (4%) and 2 more had osteomyelitis findings according to HOES-Score. Six samples (12%) with radiologically suggestive of HO turned out to be wear-induced synovitis, SLIM Type 1. Of these cases 16 were septic (32%) and 34 aseptic (68%) revisions. Most of the HO tissue samples were classified as a low-grade. High-grade ossification-Score is rare. Higher grades of ossification seem to be associated with septic revision cases. Wear-induced synovitis potentially influences HO development. A histological scoring system for ossification grading can be derived from the data presented in this study.

[Histopathological classification principles of rheumatic joint diseases : Contribution of pathology to the diagnosis]. / Histopathologische Klassifikationsprinzipien rheumatischer Gelenkerkrankungen : Beitrag der Pathologie zur Diagnose.

Even though the diagnostics of rheumatic joint diseases are mostly based on clinical, immunoserological and imaging criteria, histopathology can also make a significant contribution. This is particularly true for clinically unclear monoarticular and periarticular diseases. The contribution of histopathology to the diagnosis of rheumatic diseases is manifold since the histopathological differential diagnosis includes the complete spectrum of synovial diseases. This heterogeneous pathogenetic spectrum is described in the joint pathology algorithm, which includes inflammatory and non-inflammatory diseases. To the latter group belong certain benign tumors such as the diffuse variant of the tenosynovial giant cell tumor, lipoma, hemangioma, vascular malformations and synovial chondromatosis. Additionally, the rare group of storage diseases should be kept in mind. Inflammatory diseases can be discriminated into crystal-induced arthropathies mainly such as gout and pseudogout, into granulomatous diseases such as tuberculosis and foreign-body inoculations, and finally into the large group of non-granulomatous, non-infectious synovitis. This large group is by far the most common, and it often causes difficulties in assigning the histopathological findings to a concrete rheumatologic diagnosis. In this context the synovitis score should be applied as a diagnostic device in these cases, leading to the diagnosis of a low-grade synovitis (which is associated with degenerative arthropathies) or of a high-grade synovitis (associated with rheumatic diseases). Identification of crystals and crystal-like deposits should be carried out with the application of the joint particle algorithm which addresses the identification of endogenous and non-endogenous particle deposits in the synovial tissues. Additionally, the synovitis-score may be used for evaluation of arthritis-progresssion and for the evaluation of inflammation-regression as a consequence of therapy with biologicals.

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

BACKGROUND: The 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. METHODS: The 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. RESULTS: All 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. CONCLUSIONS: The 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.

[Pathophysiology of aseptic femoral head necrosis: Pathogenesis and histopathological differential diagnosis]. / Pathophysiologie der aseptischen Hüftkopfnekrose: Pathogenese und histopathologische Differenzialdiagnostik.

BACKGROUND: Aseptic osteonecrosis is characterized by a complete death of the tissue (necrosis), more specifically, an ischemic necrosis of the lamellar bone tissue. The denotation aseptic refers to causal pathogenesis; therefore, it is not a matter of an infectious, septic-induced bone necrosis as in the case of acute infectious osteomyelitis. Formal pathogenesis leads to either (1) a hypoperfusion of the lamellar bone in the sense of an ischemic necrosis or (2) to directly induced damage of osteocytes and osteoblasts, which causes aseptic osteonecrosis. CAUSE: The causes of hypoperfusion/ischemia are manifold and entail vascular malformations, coagulopathies, haemoglobinopathies, thrombotic embolisms, myeloproliferative illnesses, air embolisms, decompression-caused illnesses, macro as well as micro traumata and, finally, vasculitis with necrosis, which complete the vascular-induced spectrum. Direct toxic damage to the osteocytes and osteoblasts is primarily caused by alcohol abuse, medical drug therapies (i. e. chemotherapeutic substances or cortisone) and disorders of the lipid embolism. Contemporary molecular and cellular models of pathogenesis assume a so-called dysbalance of the catabolic and anabolic osseous metabolism in osteocytes and osteoblasts. The RANKL-RANK system, the ROS system and PPAR-gamma signal transduction are involved in the molecular pathogenesis. DIFFERENTIAL DIAGNOSIS: The most relevant histopathologic differential diagnosis entails the complete spectrum of focal osseous changes among which osteonecrosis can occur to a diverse extent: infectious osteomyelitis, chronic immunologic induced osteomyelitis, pseudoarthrosis, infected pseudoarthrosis, bone fractures and malignant metastatic intraosseous diseases and non-metastatic intraosseous malignant diseases.

[Arthur Vick Prize 2017 of the German Society of Orthopaedic Rheumatology]. / Arthur-Vick-Preis der Deutschen Gesellschaft für Orthopädische Rheumatologie 2017.

The German Society of Orthopaedic Rheumatology (DGORh) honored Prof. Dr. med. Veit Krenn (MVZ-ZHZMD-Trier) with the Arthur Vick Prize 2017. With this award, scientific results with high impact on the diagnosis, therapy and pathogenetic understanding of rheumatic diseases are honored. In cooperation with pathologists and colleagues from various clinical disciplines Prof. Dr. med. Veit Krenn developed several histopathologic scoring systems which contribute to the diagnosis and pathogenetic understanding of degenerative and rheumatic diseases. These scores include the synovitis score, the meniscal degeneration score, the classification of periprosthetic tissues (SLIM classification), the arthrofibrosis score, the particle score and the CD15 focus score. Of highest relevance for orthopedic rheumatology is the synovitis score which is a semiquantitative score for evaluating immunological and inflammatory changes of synovitis in a graded manner. Based on this score, it is possible to divide results into low-grade synovitis and high-grade synovitis: a synovitis score of 1-4 is called low-grade synovitis and occurs for example in association with osteoarthritis (OA), post-trauma, with meniscal lesions and hemochromatosis. A synovitis score of 5-9 is called high-grade synovitis, e.g. rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection and reactive arthritis as well as peripheral arthritis with Bechterew's disease (sensitivity 61.7%, specificity 96.1%). The first publication (2002) and an associated subsequent publication (2006) of the synovitis score has led to national and international acceptance of this score as the standard for histopathological assessment of synovitis. The synovitis score provides a diagnostic, standardized and reproducible histopathological evaluation method for joint diseases, particularly when this score is applied in the context with the joint pathology algorithm.

15 years of the histopathological synovitis score, further development and review: A diagnostic score for rheumatology and orthopaedics.

The histopathological synovitis score evaluates the immunological and inflammatory changes of synovitis in a graduated manner generally customary for diagnostic histopathological scores. The score results from semiquantitative evaluation of the width of the synovial surface cell layer, the cell density of the stroma and the density of the inflammatory infiltration into 4 semiquantitative levels (normal 0, mild 1, moderate 2, severe 3). The addition of these values results in a final score of 0-9 out of 9. On the basis of this summation the condition is divided into low-grade synovitis and high-grade synovitis: A synovitis score of 1 to≤4 is called low-grade synovitis (arthrosis-associated/OA synovitis, posttraumatic synovitis, meniscopathy-associated synovitis and synovitis with haemochromatosis). A synovitis score of≥5 to 9 is called high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme arthritis, postinfection/reactive arthritis and peripheral arthritis with Bechterew's disease). By means of the synovitis score it is therefore possible to distinguish between degenerative/posttraumatic diseases (low-grade synovitis) and inflammatory rheumatic diseases (high-grade synovitis) with a sensitivity of 61.7% and a specificity of 96.1%. The diagnostic accuracy according to ROC analysis (AUC: 0.8-0.9) is good. Since the first publication (2002) and an associated subsequent publication (2006), the synovitis score has nationally and internationally been accepted for histopathological assessment of the synovitis. In a PubMed data analysis (status: 14.02.2017), the following citation rates according to Cited by PubMed Central articles resulted for the two synovitis score publications: For DOI: 10.1078/0344-0338-5710261 there were 29 Cited by PubMed Central articles and for the second extended publication DOI:10.1111/j.1365-2559.2006.02508 there were 44 Cited by PubMed Central articles. Therefore a total of 73 PubMed citations are observed over a period of 15 years, which demonstrates an international acceptance of the score. This synovitis score provides for the first time a diagnostic, standardised and reproducible histopathological evaluation method enabling a contribution to the differential diagnosis of chronic inflammatory general joint diseases. This is particularly the case by incorporation into the joint pathology algorithm. To specify the synovitis score an immunohistochemical determination of various inflammation-relevant CD antigens is proposed to enable a risk stratification of high-grade synovitis (e.g.: progression risk and sensitivity for biologicals).

[Fifteen years of the histopathological synovitis score : Review and further developments of a diagnostic score]. / 15 Jahre histopathologischer Synovialitis-Score : Rückblick und Weiterentwicklung eines diagnostischen Scores.

The histopathological synovitis score evaluates in a graded approach, as is largely usual for diagnostic histopathological scores, the immunological and inflammatory changes caused by synovitis. A synovitis score of between 1 and ≤ 4 is classified as low-grade (osteoarthritis-related synovitis, post-traumatic synovitis, meniscopathy-related synovitis and synovitis in hemochromatosis). Synovitis scores of between ≥ 5 and 9 are classified as high-grade synovitis (rheumatoid arthritis, psoriatic arthritis, Lyme's arthritis, post-infection/reactive arthritis and peripheral arthritis in Bechterew disease); sensitivity is 61.7% and sensitivity 96.1%. According to receiver operating characteristic (ROC) analysis (AUC: 0.8-0.9), diagnostic value is good. National and international acceptance of the synovitis score has grown since the first publication in 2002 and a related follow-up publication in 2006. PubMed data analysis (as of 11.01.2017) yielded the following citation values according to "cited by PubMed Central articles" for two publications relating to the synovitis score: there were 29 cited-by-PubMed articles for DOI: 10.1078/0344-0338-5710261 , and 44 cited-in-PubMed articles for the second publication, DOI: 10.1111/j.1365-2559.2006.02508 . This makes a total of 73 PubMed citations over a period of 15 years, thereby evidencing the score's international acceptance. Immunohistochemical determination of a number of CD antigens relevant to inflammation has been proposed to further specify the synovitis score for the purposes of risk stratification of high-grade synovitis (e.g., risk of progression and sensitivity to biological agents).

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

INTRODUCTION: The 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). METHODS: The 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. RESULTS: The 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). CONCLUSION: As 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.

[Endoprosthesis failure in the ankle joint : Histopathological diagnostics and classification]. / Endoprothesenversagen im oberen Sprunggelenk : Histopathologische Diagnostik und Klassifikation.

INTRODUCTION: Endoprostheses of the ankle joint show higher revision rates of 3.29 revisions per 100 component years. The aims of this study were the application and modification of the consensus classification of the synovia-like interface membrane (SLIM) for periprosthetic failure of the ankle joint, the etiological clarification of periprosthetic pseudocysts and a detailed measurement of proliferative activity (Ki67) in the region of osteolysis. MATERIAL AND METHOD: Tissue samples from 159 patients were examined according to the criteria of the standardized consensus classification. Of these, 117 cases were derived from periprosthetic membranes of the ankle. The control group included 42 tissue specimens from the hip and knee joints. Particle identification and characterization were carried out using the particle algorithm. An immunohistochemical examination with Ki67 proliferation was performed in all cases of ankle pseudocysts and 19 control cases. RESULTS: The consensus classification of SLIM is transferrable to endoprosthetic failure of the ankle joint. Periprosthetic pseudocysts with the histopathological characteristics of the appropriate SLIM subtype were detectable in 39 cases of ankle joint endoprostheses (33.3%). The mean value of the Ki67 index was 14% and showed an increased proliferation rate in periprosthetic pseudocysts of the ankle (p-value 0.02037). CONCLUSION: In periprosthetic pseudocysts an above average higher detection rate of type 1 SLIM induced by abrasion (51.3%) with an increased Ki67 proliferation fraction (p-value 0.02037) was found, which can be interpreted as local destructive intraosseus synovialitis. This can be the reason for formation of pseudocystic osteolysis caused by high mechanical stress in ankle endoprostheses. A simplified diagnostic classification scoring system of dysfunctional endoprostheses of the ankle is proposed for collation of periprosthetic pseudocysts, ossifications and the Ki67 proliferation fraction.

International consensus on the definition and classification of fibrosis of the knee joint.

AIMS: The aim of this consensus was to develop a definition of post-operative fibrosis of the knee. PATIENTS AND METHODS: An international panel of experts took part in a formal consensus process composed of a discussion phase and three Delphi rounds. RESULTS: Post-operative fibrosis of the knee was defined as a limited range of movement (ROM) in flexion and/or extension, that is not attributable to an osseous or prosthetic block to movement from malaligned, malpositioned or incorrectly sized components, metal hardware, ligament reconstruction, infection (septic arthritis), pain, chronic regional pain syndrome (CRPS) or other specific causes, but due to soft-tissue fibrosis that was not present pre-operatively. Limitation of movement was graded as mild, moderate or severe according to the range of flexion (90° to 100°, 70° to 89°, < 70°) or extension deficit (5° to 10°, 11° to 20°, > 20°). Recommended investigations to support the diagnosis and a strategy for its management were also agreed. CONCLUSION: The development of standardised, accepted criteria for the diagnosis, classification and grading of the severity of post-operative fibrosis of the knee will facilitate the identification of patients for inclusion in clinical trials, the development of clinical guidelines, and eventually help to inform the management of this difficult condition. Cite this article: Bone Joint J 2016;98-B:1479-88.

[Adverse reactions to metal orthopedic implants after knee arthroplasty]. / Adverse Reaktionen gegenüber orthopädisch-chirurgischen Metallimplantaten nach Kniegelenkersatz.

Based on several clinical examples, the range of adverse or hypersensitive reactions to metal implants especially after total knee replacement are presented. In general, we found the patients to generally be women who present with pain, swelling, and local or generalized eczema. Some also present with early aseptic loosening mainly in the first 4 years after implantation. For these patients, a detailed allergy-specific history should be taken and a patch test should be performed; if necessary, blood ion levels should be evaluated to exclude cobaltism. Before revision surgery and exchange of the implant we always perform arthroscopic inspection to obtain biopsies for microbiology and histopathology. Using the Consensus Classification a good evaluation for planning revision with the different implant options is possible.