A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty.

Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/ß will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/ß induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/ß treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/ß availability and not their ability to respond to it.

Fibrosis is a common outcome following total knee arthroplasty.

Total knee arthroplasty (TKA) is one of the most successful orthopaedic procedures that alleviates pain and restores function in patients with degenerative knee joint diseases. Arthrofibrosis, abnormal scarring in which dense fibrous tissue prevents normal range of motion, develops in ~3-10% of TKA patients. No prophylactic intervention is available and treatment is restricted to aggressive physiotherapy or revision surgery. Tissue was collected from patients undergoing primary (n = 30) or revision (n = 27) TKA. Revision patients were stratified as non-arthrofibrotic and arthrofibrotic. Tissue was macroscopically and histologically compared to improve our understanding of the pathophysiology of arthrofibrosis. Macroscopically, tissue from primary TKA presents as homogenous, fatty tissue whereas tissue from revision TKA presents as dense, pigmented tissue. Histologically, there was dramatic tissue remodelling, increased collagen deposition and increased (myo)fibroblast staining in tissue from revision TKA. Significantly, tissue architecture was similar between revision patients regardless of clinically diagnosis. There are significant differences in architecture and composition of tissue from revision TKA over primary TKA. Surprisingly, whether revision TKA were clinically diagnosed as arthrofibrotic or non-arthrofibrotic there were still significant differences in fibrotic markers compared to primary TKA suggesting an ongoing fibrotic process in all revision knees.

Use of porous trabecular metal augments with impaction bone grafting in management of acetabular bone loss.

BACKGROUND: The use of impaction grafting in revisions with larger acetabular bone defects has mixed outcomes and sometimes high failures rates. PATIENTS AND METHODS: This prospective, single-center study involved a consecutive series of 24 patients who underwent complex reconstruction of the acetabulum using a trabecular metal augment, impaction bone grafting, and a cemented high-density polyethylene cup. Patients were followed for median 5 (3-7) years. RESULTS: The 2-year WOMAC pain, function, and stiffness scores improved, as did certain components (bodily pain, physical function, role physical, role emotional, physical component score, and social function) of the SF-36 (p < 0.05). 23 of the patients were very satisfied with the overall outcome of the surgery and would have undergone the surgery again for a similar problem, and 19 reported great improvement in their quality of life after surgery. Radiographs at the latest follow-up revealed incorporation of the augment with mean change in acetabular component inclination of less than 1 degree (p > 0.05) and cup migration of less than 5 mm in both horizontal and vertical axes (p > 0.05). 1 patient required further revision at 13 months and was found to have a fractured augment at re-revision. INTERPRETATION: This study shows that trabecular metal augments are effective in filling the bone defect and provide a stable foundation for impaction bone grafting. We found satisfactory clinical and radiographic results using this technique, with low failure rate at a median follow-up time of 5 years.

Functional outcome following aseptic single-stage revision knee arthroplasty.

PURPOSE: This study attempts to quantify the influence of constraint and various indications upon functional outcome following aseptic first-time revision knee arthroplasty. METHODS: A single-centre prospective study was performed to examine the outcome for 175 consecutive total revision knee replacements performed between 2003 and 2008 with a minimum follow-up of 2 years. Patient-reported outcome data were used to determine the influence of final level of component constraint, its relationship with primary indication for surgery and the predictor variable for functional outcome at 1 year. RESULTS: All patients were found to have a significant improvement for WOMAC pain, function and stiffness score and physical functioning, role physical, bodily pain and social functioning components of SF-36 score. About 69% were satisfied with the overall procedure. WOMAC function, pain and stiffness score was significantly worse for patients revised for instability (27%) compared to that for aseptic loosening (46%). A significantly higher proportion of patients were satisfied with the procedure, had a better quality of life and would have the surgery again in the aseptic loosening group as compared to the instability group. Revision to a higher level of constraint did not improve knee function irrespective of the primary indication for surgery. CONCLUSION: This study has found that revision for instability, irrespective of choice of new device, was met with significantly poorer functional outcome. The level of constraint did not influence functional outcome. LEVEL OF EVIDENCE: II.

Techniques to improve the shear strength of impacted bone graft: the effect of particle size and washing of the graft.

BACKGROUND: When fresh morselized graft is compacted, as in impaction bone-grafting for revision hip surgery, fat and marrow fluid is either exuded or trapped in the voids between particles. We hypothesized that the presence of incompressible fluid damps and resists compressive forces during impaction and prevents the graft particles from moving into a closer formation, thus reducing the graft strength. In addition, viscous fluid such as fat may act as an interparticle lubricant, thus reducing the interlocking of the particles. METHODS: We performed mechanical shear testing in the laboratory with use of fresh-frozen human femoral-head allografts that had been passed through different orthopaedic bone mills to produce graft of differing particle-size distributions (grading). RESULTS: After compaction of fresh graft, fat and marrow fluid continued to escape on application of normal loads. Washed graft, however, had little lubricating fluid and better contact between the particles, increasing the shear resistance. On mechanical testing, washed graft was significantly (p < 0.001) more resistant to shearing forces than fresh graft was. This feature was consistent for different bone mills that produced graft of different particle-size distributions and shear strengths. CONCLUSIONS: Removal of fat and marrow fluid from milled human allograft by washing the graft allows the production of stronger compacted graft that is more resistant to shear, which is the usual mode of failure. Further research into the optimum grading of particle sizes from bone mills is required.