Michelle Bardgett

Fibroblasts Promote Inflammation and Pain via IL-1α Induction of the Monocyte Chemoattractant Chemokine (C-C Motif) Ligand 2

Fibroblasts persist within fibrotic scar tissue and exhibit considerable phenotypic and functional plasticity. Herein, we hypothesized that scar-associated fibroblasts may be a source of stress-induced inflammatory exacerbations and pain. To test this idea, we used a human model of surgery-induced fibrosis, total knee arthroplasty (TKA). Using a combination of tissue protein expression profiling and bioinformatics, we discovered that many months after TKA, the fibrotic joint exists in a state of unresolved chronic inflammation. Moreover, the infrapatellar fat pad, a soft tissue that becomes highly fibrotic in the post-TKA joint, expresses multiple inflammatory mediators, including the monocyte chemoattractant, chemokine (C-C motif) ligand (CCL) 2, and the innate immune trigger, IL-1α. Fibroblasts isolated from the post-TKA fibrotic infrapatellar fat pad express the IL-1 receptor and on exposure to IL-1α polarize to a highly inflammatory state that enables them to stimulate the recruitment of monocytes. Blockade of fibroblast CCL2 or its transcriptional regulator NF-κB prevented IL-1α–induced monocyte recruitment. Clinical investigations discovered that levels of patient-reported pain in the post-TKA joint correlated with concentrations of CCL2 in the joint tissue, such that the chemokine is effectively a pain biomarker in the TKA patient. We propose that an IL-1α–NF-κB–CCL2 signaling pathway, operating within scar-associated fibroblasts, may be therapeutically manipulated for alleviating inflammation and pain in fibrotic joints and other tissues.

Three groups of dissatisfied patients exist after total knee arthroplasty: early, persistent, and late

Aims The primary aim of this study was to assess whether patient satisfaction one year after total knee arthroplasty (TKA) changed with longer follow‐up. The secondary aims were to identify predictors of satisfaction at one year, persistence of patient dissatisfaction, and late onset dissatisfaction in patients that were originally satisfied at one year. Patients and Methods A retrospective cohort consisting of 1369 patients undergoing a primary TKA for osteoarthritis that had not undergone revision were identified from an established arthroplasty database. Patient demographics, comorbidities, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and Short Form 12 (SF‐12) questionnaire scores were collected preoperatively, and one and five years postoperatively. In addition, patient satisfaction was assessed at one and five years postoperatively. Logistic regression analysis was used to identify independent predictors of satisfaction at one and five years. Results The overall rate of satisfaction did not change from one (91.7%, n = 1255) to five (90.1%, n = 1234) years (p = 0.16). Approximately half (n = 53/114) of the patients who were dissatisfied at one year became satisfied with their TKA at five years, whereas 6% (n = 74/ 1255) of those who were satisfied at one year became dissatisfied at five years. At one year, patients with lung disease (p = 0.04), with depression (p = 0.001), with back pain (p < 0.001), undergoing unilateral TKA (p = 0.001), or with a worse preoperative WOMAC pain score (p = 0.04) were more likely to be dissatisfied. Patients with gastric ulceration (p = 0.04) and a worse WOMAC stiffness score (p = 0.047) were at increased risk of persistent dissatisfaction at five years. In contrast, a worse WOMAC pain score (p = 0.01) at one year was a predictor of dissatisfaction in previously satisfied patients at five years. Conclusion Three groups of dissatisfied patients exist after TKA: ‘early’ dissatisfaction at one year, ‘persistent’ dissatisfaction with longer follow‐up, and ‘late’ dissatisfaction developing in previously satisfied patients at one year. All three groups have different independent predictors of satisfaction, and potentially addressing risk factors specific to these groups may improve patient outcome and their satisfaction.

Return to work after knee replacement: a qualitative study of patient experiences

Objective An increasing number of patients in the working population are undergoing total knee replacement (TKR) for end-stage osteoarthritis. The timing and success of return to work is becoming increasingly important for this group of patients with social and economic implications for patients, employers and society. There is limited understanding of the patient variables that determine the ability to return to work. Our objective was (from the patients perspective) to gain an insight into the factors influencing return to work following knee replacement. Setting and participants This qualitative study was undertaken in a secondary-care setting in a large teaching hospital in the north of England. Semistructured interviews were carried out with 10 patients regarding their experiences of returning to work following TKR. Outcomes Interviews were transcribed and analysed using a qualitative thematic approach to identify the factors influencing return to work from the patients perspective. Results Three themes were identified that influenced the process of return to work, from the patients perspective. These were delays in surgical intervention, limited and often inconsistent advice from healthcare professionals regarding return to work, and finally the absence of rehabilitation to optimise patients recovery and facilitate return to work. Conclusions There is currently no consistent process to optimise return to work for patients of working age after TKR. The impact of delayed surgical intervention, limited advice regarding return to work, and a lack of work-focused rehabilitation, all contribute to potential delays in successful return to work. There is a need to change the focus of healthcare provision for this cohort of patients, and provide a tailored healthcare intervention to optimise patient outcomes.

Synovectomy during total knee arthroplasty: a pilot single-centre randomised controlled trial.

BackgroundTotal knee arthroplasty (TKA) is an effective procedure for late-stage osteoarthritis (OA) of the knee; however, up to 20% of patients remain dissatisfied. In some patients, this may be due to residual inflammation of the synovium. Our aim was to perform the first randomised controlled trial (RCT) of synovectomy during TKA for patients with macroscopically inflamed synovium. The main objectives were to assess recruitment rates, protocol adherence and outcomes relating to safety such as haemoglobin decrease and adverse events. We also collected data on patient-reported outcomes.MethodsWe performed a single-centre pilot RCT. Patients with a macroscopically inflamed synovium were randomised to receive synovectomy versus a control group that did not undergo synovectomy. We determined feasibility by measuring patient enrolment, completeness of follow-up, and safety via haemoglobin decrease and documentation of adverse events.ResultsWe screened 360 patients with 260 deemed ineligible or could not be recruited. From the 100 eligible patients, 54 were enrolled and 40 progressed through to randomisation. All made it to the 12-month follow-up, indicating good protocol adherence. There were no major differences in adverse events or haemoglobin decrease demonstrating acceptable safety. Outcomes relating to satisfaction were reliably obtained.ConclusionsPatients with macroscopically inflamed synovium of the knee who are due to undergo TKA can be reliably recruited to a randomised trial and synovectomy can be performed safely. A large number is needed to be screened to identify eligible participants, and therefore, a multi-centre trial would be required to assess whether routine synovectomy would improve outcomes in these patients.Trial registrationISRCTN, ISRCTN31010214. Registered 6 October 2016—retrospectively registered