R. G. H. H. Nelissen

Inflammatory Cells in Patients with Endstage Knee Osteoarthritis: A Comparison between the Synovium and the Infrapatellar Fat Pad

Objective. To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA. Methods. Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0–100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed. Results. Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09–1.02, p = 0.02). Conclusion. Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.

Association of pain in knee osteoarthritis with distinct patterns of synovitis

To determine possible patterns of synovitis on contrast‐enhanced magnetic resonance imaging (CE‐MRI) and its relation to pain and severity in patients with radiographic knee osteoarthritis (OA).

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.

Erythropoietin to reduce allogeneic red blood cell transfusion in patients undergoing total hip or knee arthroplasty

To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta‐analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes.

Healthcare costs and loss of productivity in patients with trapeziometacarpal osteoarthritis

The objective of this study was to analyse healthcare and productivity costs in patients with trapeziometacarpal osteoarthritis. We included 161 patients who received surgery or steroid injection and calculated their healthcare costs in Euro (€) over 1 year. Patients filled out the Work Productivity and Activity Impairment Questionnaire to assess loss of productivity at baseline, and after 3, and 12 months. In the surgical group, loss of productivity among employed patients first increased and then decreased (50%, 64%, and 25% at 0, 3, and 12 months). Productivity was more stable over time in the injection group (52%, 38%, and 48%). In the surgical group, estimated total annual healthcare and productivity costs were €5770 and €5548, respectively. In the injection group, healthcare and productivity costs were €348 and €3503. These findings highlight the need for assessing productivity costs to get a comprehensive view of the costs associated with a treatment. Level of Evidence III

Degree of synovitis on MRI is correlated with histological and macroscopic features of synovial tissue inflammation in knee osteoarthritis

Background and objectives Synovitis is often present on MRI of OA knees and is an important determinant of pain. To better understand the nature of synovitis seen on MRI the authors compared microscopic and macroscopic features of synovial tissue inflammation with synovitis grade on contrast enhanced (CE) MRI. Methods and methods Twenty-two patients (mean age 61±7 years, 73% women, mean BMI 30±5 kg/mm2) with symptomatic radiographic knee OA attending the rheumatology outpatient clinic were included. Arthroscopy of the index knee was performed and macroscopic features (neovascularisation, villi, fibrin and hyperplasia) were scored (0–4). Furthermore, 15–20 synovial biopsies per knee were obtained. After H&E staining, synovial tissue samples were microscopically scored on features: synovial lining layer hyperplasia/enlargement, activation of resident cells/stroma and degree of inflammatory infiltrates. Each feature was scored from 0–3 and a total sum score per patient was devised. Mean total scores (0–9) by three observers were used. Saggital and axial T1-weighted CE MRI images (3T) were used to semi quantitatively score synovitis at 11 different sites according to Guermazi et al, ranging from 0–22.1 Self reported pain was assessed by visual analogue scale (VAS, 0–100). Pearson correlations adjusted for age were used for correlation between total histology synovitis score and total MRI score. Spearman ρ correlations were used for correlation between total histology score and macroscopic features. Both were calculated by SPSS 16.0. Results The mean (SD) synovitis score on MRI was 7.8 (3.9), representing a mild synovitis and mean (SD) histology score was 2.1 (1.5). Median (range) score of macroscopic features (0–4) were 2.0 (1.0–4.0) for neovascularisation, 1.0 (0.0–3.0) for hyperplasia, 2.0 (0.0–4.0) for villi and 2.0 (0.0–3.0) for fibrin. Synovitis score on MRI correlated significantly with microscopic synovitis score (r=0.5, p=0.019] and macroscopic neovascularisation score (r=0.6, p=0.002) and hyperplasia (r=0.4, p=0.40). Furthermore statistically significant correlation between microscopic synovitis score and macroscopic neovascularisation (r=0.5, p=0.012) existed. No significant correlations with VAS pain were seen. Conclusions Synovitis severity on T1 weighted CE MRI images is significantly correlated with both macroscopic and microscopic features of synovitis in patients with knee OA. No association with severity of pain was seen. Therefore, CE MRI evaluation is a reliable, non invasive way to determine synovitis severity in OA patients.

SAT0505 Self-reported knee instability associated with pain and activity limitations prior and one year after total knee arthroplasty in patients with knee osteoarthritis

Background Sixty to 80% of the patients with knee osteoarthritis (OA) reported self-reported knee joint instability, which was associated with pain and activity limitations. One previous randomized control trial described the prevalence of retained self-reported knee joint instability after total knee arthroplasty (TKA) (32%). To better understand self-reported knee joint instability in usual care there is a need to replicate and extend the results. Objectives The aims of the study were to determine (i) the prevalence of self-reported knee instability prior and one year after TKA, (ii) the associations between self-reported knee instability, pain, activity limitations and quality of life prior and one year after TKA, (iii) the course of self-reported knee instability over time and (iv) the associations between retained knee instability, pain, activity limitations and quality of life. Methods Consecutive patients with knee OA undergoing primary TKA, extracted from the Longitudinal Leiden Orthopaedics and Outcomes of OsteoArthritis Study (LOAS Study), were included. Self-reported knee joint instability and the Knee injury and Osteoarthritis Outcome Score (KOOS) Pain, Activity Daily Living (ADL) and QoL subscales (0–100; worst-best) were assessed by questionnaires prior and one year after surgery. Multivariable regression analyses were performed to determine associations between knee joint instability, pain, activity limitations and quality of life, adjusted for potential confounders including age, sex, comorbidities, physical activity and preoperative frailty. Results 908 patients were included of which 649 patients (72%) reported preoperative knee joint instability (mean age 67 years (SD8.6), 453 females (70%)) and 187 patients (21%) postoperative knee joint instability. Preoperative knee joint instability was associated with preoperative KOOS Pain (B-7.2;95% CI-10.9–3.5) and ADL (B3.8;95% CI-7.5–0.09), but not QoL (B-0.4;95% CI-2.1–1.2). In addition, postoperative knee joint instability was associated with postoperative KOOS Pain (B-13.5;95% CI-17.0–10.0), ADL (B-15.1,95% CI-18.4–11.8) and QoL (B-11.0;95% CI-13.5–8.5). Among the patients with preoperative self-reported knee joint instability, 165 patients (25%) retained knee instability and among the patients with no preoperative self-reported knee joint instability, 22 (8%) developed knee instability one year after surgery. After adjusting for baseline scores and potential confounders, retained knee joint instability was associated with postoperative KOOS Pain (B-19.6;95% CI-30.9–8.3), ADL (B-16.5;95% CI-27.0–5.9) and QoL (B-13.0;95% CI-17.9–8.1). Conclusions In usual care, knee joint instability is prevalent one year after TKA (21%). Reported knee joint instability is associated with more pain, worse physical function (pre- and postoperatively) and worse Qol postoperatively. Besides, retained knee joint instability was associated with worse pain, physical function and QoL. This emphasizes the importance of further research into the genesis of pre- and postoperative knee joint instability. Acknowledgements The study was funded by the Dutch Arthritis Foundation (DAF). Disclosure of Interest None declared

SAT0001 Lack of obesity-related features in adipocytes and inflammatory cells in the infrapatellar fat pad (IFP)

Background Obesity is associated with the development and progression of osteoarthritis (OA), both for weight-bearing and non-weight bearing joints. Several lines of research indicate that obesity-related systemic factors, such as adipose tissue-derived factors, could be involved in this association. The infrapatellar fat pad (IFP) is an adipose tissue depot localized in the knee joint. and could mediate obesity-associated effects. However, it is currently unknown whether and how obesity affects IFP. Objectives To investigate the presence of obesity-related features in adipocytes and infiltrating immune cells in the IFP of OA patients. Methods Knee OA patients (N=155: 68% women, mean age 65 years, mean (SD) BMI 29.9 kg/m2 (5.7)) were recruited: IFP volume was determined by MRI in 79 knee OA patients, while IFP and subcutaneous adipose tissue (SCAT) were obtained from 106 patients undergoing arthroplasty. Crown-like structures (CLS) were determined using immunohistochemistry. Adipocyte size was determined by light microscopy and histology. Stromal vascular fraction (SVF) cells were characterized by flow cytometry. Results IFP volume (mean (SD) 23.6 (5.4) mm3) was associated with height, but not with BMI or other obesity-related features such as waist circumference, fat percentage and waist to hip ratio. The volume of IFP adipocytes did not correlate with BMI, in contrast to SCAT adipocytes. Few CLS were observed in IFP and their number did not differ between individuals with high and low BMI. Moreover, high BMI was not associated with higher infiltrating immune cell numbers in IFP, nor with changes in immune cell populations. Likewise, no molecular differences were observed in FCM-secreted factors between high and low BMI, except for an increased TNFa secretion in obesity. Since obesity is usually associated with a shift towards pro-inflammatory macrophages in conventional adipose tissue, we have extensively characterized IFP macrophages. Surprisingly, CD206 and CD163, usually associated with an anti-inflammatory phenotype were the most abundantly expressed surface markers on macrophages (81% and 41% respectively). In contrast, cytokine profiles revealed a pro-inflammatory phenotype of the total macrophage population, with cells producing predominantly IL-6 and TNFα, but little IL-10. Interestingly, the CD163+ macrophages were bigger and had a more activated and pro-inflammatory phenotype than their CD163- counterparts. However, no association with BMI could be observed for different macrophage populations or their cytokines. Conclusions BMI-related features usually observed in SCAT and visceral adipose tissue could not be detected in IFP of OA patients, a fat depot implicated in OA pathogenesis. Disclosure of Interest None declared

SAT0701 Towards diagnosis-specific lifetime risks for total hip arthroplasty revision surgery

Background An important aspect regarding optimal timing of primary hip arthroplasty (THA) is to weigh the benefit associated with the primary surgery at a certain point in time against the risk for revision surgery. Revision surgery should be avoided, as outcomes after revision surgery are less favourable than outcomes after primary surgery. Information on lifetime revision risks is needed to guide decision making for individual patients regarding timing of primary surgery. Objectives Our aim was to provide the 7 year cumulative percentages for revision surgery stratified for diagnosis, sex, type of fixation and age at which primary THA was performed. Methods Data on arthroplasties was available from the Dutch Arthroplasty Register (LROI), a nationwide population-based registry with information on all joint arthroplasties in the Netherlands from 2007 onwards. For the current study, all patients who received a primary THA in the period 2007 to 2015 were included except patients with a metal on metal prosthesis, patients with a hybrid or reversed hybrid fixation type or patients with revision surgery without primary surgery registered. Revision surgery was defined as any change of one or more components of the prosthesis. For the current study age at primary surgery, diagnosis, sex, type of fixation (uncemented, cemented) and survival (alive/dead) and revision of prosthesis (yes/no) were extracted from the LROI database. Diagnosis was dichotomized into osteoarthritis (OA) and other diagnoses. Annual revision risks were calculated for each subsequent year after primary arthroplasty by dividing the number of revisions by the total number of patients at risk during that year. The risks were stratified according to the underlying diagnosis, sex, age at primary arthroplasty and fixation type. In addition cumulative annual revision percentages were calculated for the full follow-up period. Furthermore we estimated the percentage of avoided OA revisions by assuming that all OA patients received their primary THA 5 years later (in all age groups <85 yrs) and that the revision risks remained the same in all age categories. Results In total 134463 primary THA patients were included of whom 68% were female, 89% had OA as underlying indication and 66% of the THAs were uncemented. The 7th year cumulative risk percentage varied between 2.0 and 11.7% (Table 1). Overall cumulative revision percentages were higher in younger age categories (Table 1), with the exception of a 11.7% revision in the group aged 85–90 yrs (uncemented, male, other diagnosis), but this finding is likely due to chance as this group existed of 67 patients. We estimated that by delaying THA for 5 years, a total of 197 revision surgeries (4.4% of all revision surgeries) could be avoided, 48 (14.0%) in the OA male cemented group, 11 (0.9%) in the OA male uncemented group, 69 (3.3%) in the OA female cemented group and 69 (8.6%) in the female uncemented group. This could result in a yearly cost reduction of approximately 4 million euros. Conclusions Cumulative 7th year risk percentages decreased by age in all different categories. By delaying the primary THA surgery, revisions might be avoided thereby resulting in cost reduction. Disclosure of Interest None declared

AB0844 Determinants of Returning to Work 12 Months After Total Joint Surgery: Differences Between Total Hip Arthroplasty and Total Knee Arthroplasty

Background The majority of the patients undergoing Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA) returns to work postoperatively, but the absolute number of patients who do not return to work remains substantial. Little is known about factors limiting return to work1, Objectives To identify factors related to return to work after THA and TKA one year postoperatively. Methods This one-year prospective cohort study included patients who were assessed preoperatively and one-year postoperatively, aged 65 years or younger, and who provided information on their work status. Assessments included a questionnaire and/or telephone interview on work status. The outcome of return to work was divided into full return to work vs. partial or no return to work. Potential determinants included the following preoperative characteristics: physical hip/knee-job demands (classified into light, medium or heavy), the amount of working hours a week, self-employement, sick leave duration, granted disability benefits, presence of work adaptions and expectations of returning to work. Logistic regression analyses were employed to determine factors associated partial/no return to work in all patients, controlling for type of surgery (THA or TKA). Results Sixty-seven THA patients (mean age 56 years; SD 6.6, 33 females (49%)) and 56 TKA patients (mean age 56 years; SD 5.7, 31 females (55%)) were included. The mean amount of work hours a week preoperatively was 32 hours (SD 12.5) in THA patients and 31 hours (SD 12.3) in TKA patients. 53/67 THA patients (79%) and 40/56 TKA patients (71%) returned to work fully one-year post-operatively (same mean amount of work hours), whereas 5/67 THA patients (7%) and 7/56 TKA patients (13%) did not return to work at all and 9/67 THA patients (13%) and 9/56 TKA patients (16%) returned to work but less hours than preoperatively (mean decrease of work hours per week -17 hours (SD 11.5, P=0.002) in THA and -16 hours (SD 12.4, P=0.005) in TKA) The THA patients who returned to work partially or not had a lower educational level (P=0.006), were more often self-employed (P=0.009) and were more often absent from work due to hip complaints preoperatively than those fully returning to work (P=0.002). In the TKA group of patients there were no significant differences in characteristics of patients returning to work fully or not. In the multivariable logistic regression analyses, being self-employed (OR 7.4, 95%, CI 1.5-35.8), preoperative absence from work (OR 10.8, 95% CI 2.8-4.8) and working more hours preoperatively (OR 1.03, 95% CI 0.99-1.1) were factors significantly associated with partial/no return to work. Conclusions Self-employment, working more hours and being absent from work preoperatively remained determinants for partial/no return to work after correcting for type of prothesis. These findings underline the need to study return to work after THA and TKA separately. References C.Tilbury, et al., Return to work after total hip and knee arthroplasty: a systematic review. Rheumatology. (Oxford) 53(3), 512 (2014). Acknowledgements This study was funded by the Anna Fonds/NOREF Disclosure of Interest None declared