Lars Morawietz

AIMS: To standardize the histopathological assessment of synovial membrane specimens in order to contribute to the diagnostics of rheumatic and non-rheumatic joint diseases. METHODS AND RESULTS: Three features of chronic synovitis (enlargement of lining cell layer, cellular density of synovial stroma, leukocytic infiltrate) were semiquantitatively evaluated (from 0, absent to 3, strong) and each feature was graded separately. The sum provided the synovitis score, which was interpreted as follows: 0-1, no synovitis; 2-4, low-grade synovitis; 5-9, high-grade synovitis. Five hundred and fifty-nine synovectomy specimens were graded by two independent observers. Clinical diagnoses were osteoarthrosis (n=212), post-traumatic arthritis (n=21), rheumatoid arthritis (n=246), psoriatic arthritis (n=22), reactive arthritis (n=9), as well as controls (n=49) from autopsies of patients without joint damage. Median synovitis scores when correlated with clinical diagnoses were: controls 1.0, osteoarthritis 2.0, post-traumatic arthritis 2.0, psoriatic arthritis 3.5, reactive arthritis 5.0 and rheumatoid arthritis 5.0. The scores differed significantly between most disease groups, especially between degenerative and rheumatic diseases. A high-grade synovitis was strongly associated with rheumatic joint diseases (P<0.001, sensitivity 61.7%, specificity 96.1%). The correlation between the two observers was high (r=0.941). CONCLUSION: The proposed synovitis score is based on well-defined, reproducible histopathological criteria and may contribute to diagnosis in rheumatic and non-rheumatic joint diseases.

BACKGROUND: Reliability of measurements is a prerequisite of medical research. For nominal data, Fleiss' kappa (in the following labelled as Fleiss' K) and Krippendorff's alpha provide the highest flexibility of the available reliability measures with respect to number of raters and categories. Our aim was to investigate which measures and which confidence intervals provide the best statistical properties for the assessment of inter-rater reliability in different situations. METHODS: We performed a large simulation study to investigate the precision of the estimates for Fleiss' K and Krippendorff's alpha and to determine the empirical coverage probability of the corresponding confidence intervals (asymptotic for Fleiss' K and bootstrap for both measures). Furthermore, we compared measures and confidence intervals in a real world case study. RESULTS: Point estimates of Fleiss' K and Krippendorff's alpha did not differ from each other in all scenarios. In the case of missing data (completely at random), Krippendorff's alpha provided stable estimates, while the complete case analysis approach for Fleiss' K led to biased estimates. For shifted null hypotheses, the coverage probability of the asymptotic confidence interval for Fleiss' K was low, while the bootstrap confidence intervals for both measures provided a coverage probability close to the theoretical one. CONCLUSIONS: Fleiss' K and Krippendorff's alpha with bootstrap confidence intervals are equally suitable for the analysis of reliability of complete nominal data. The asymptotic confidence interval for Fleiss' K should not be used. In the case of missing data or data or higher than nominal order, Krippendorff's alpha is recommended. Together with this article, we provide an R-script for calculating Fleiss' K and Krippendorff's alpha and their corresponding bootstrap confidence intervals.

AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.