Effectiveness, safety, and cost-utility of a knee brace in medial knee osteoarthritis: the ERGONOMIE randomized controlled trial.

OBJECTIVE: This pragmatic, multicenter, open-label, randomized controlled trial (RCT) aimed to compare the effectiveness, safety, and cost-utility of a custom-made knee brace versus usual care over 1 year in medial knee osteoarthritis (OA). DESIGN: 120 patients with medial knee OA (VAS pain at rest >40/100), classified as Kellgren-Lawrence grade II-IV, were randomized into two groups: ODRA plus usual care (ODRA group) and usual care alone (UCA group). The primary effectiveness outcome was the change in VAS pain between M0 and M12. Secondary outcomes included changes over 1 year in KOOS (function) and OAKHQOL (quality of life) scores. Drug consumption, compliance, safety of the knee brace, and cost-utility over 1 year were also assessed. RESULTS: The ODRA group was associated with a higher improvement in: VAS pain (adjusted mean difference of -11.8; 95% CI: -21.1 to -2.5); all KOOS subscales (pain: +8.8; 95% CI: 1.4-16.2); other symptoms (+10.4; 95% CI: 2.7-18); function in activities of daily living (+9.2; 95% CI: 1.1-17.2); function in sports and leisure (+12.3; 95% CI: 4.3-20.3); quality of life (+9.9; 95% CI: 0.9-15.9), OAKHQOL subscales (pain: +14.8; 95% CI: 5.0-24.6); and physical activities (+8.2; 95% CI: 0.6-15.8), and with a significant decrease in analgesics consumption at M12 compared with the UCA group. Despite localized side-effects, observance was good at M12 (median: 5.3 h/day). The ODRA group had a more than 85% chance of being cost-effective for a willingness-to-pay threshold of €45 000 per QALY. CONCLUSIONS: The ERGONOMIE RCT demonstrated significant clinical benefits of an unloader custom-made knee brace in terms of improvements in pain, function, and some aspects of quality of life over 1 year in medial knee OA, as well as its potential cost-utility from a societal perspective.

Total knee arthroplasty for osteoarthritis secondary to extra-articular malunions.

INTRODUCTION: Post-traumatic total knee arthroplasty for extra-articular malunion requires correction of the deformity, either through asymmetrical bone resection (possibly inducing ligaments imbalance) or osteotomy at the time of arthroplasty. We report the results of a continuous multicenter, retrospective series of 78 patients (18 implants with osteotomy) with a mean 4 years of follow-up. The hypothesis is that the selected procedure requires to be based on the deformity's location and severity. PATIENTS: With a mean age of 63 years (younger in the osteotomy group), 38 patients had femoral malunion, 36 had tibial malunion, and four had a combined malunion. There were 70 frontal deformities (48 varus and 22 valgus) and 10 rotational deformities, often diaphyseal, four of which more than 20°. Twelve patients had a history of infection; eight had frontal laxity greater than 10°, and 15 a limited range of motion in flexion. In 70 cases, semi- or nonconstrained implants were used, and in eight cases more constrained implants, including four hinge prostheses. RESULTS: We observed two deep infections, one case of avulsion of the extensor mechanism, and two cases of aseptic loosening with femoral malunion and varus deformity. Two osteotomies resulted in nonunion, one with internal fixation devices mobilization requiring revision using extension rods. The function and pain scores were significantly improved. The mobility improvements were moderate but did not compromise the surgical procedure main objective. The preoperative hip-knee angle was corrected with both techniques. Only the function score gain was greater for the isolated arthroplasty procedures. DISCUSSION AND CONCLUSION: The indications for arthroplasty alone were extended to 20° varus and 15° valgus, with no major residual laxity. Beyond 10°, hinge prosthesis should be available. Associated osteotomy can correct rotational deformities that cannot be compensated with bone cuts. In deformities that are close to the joint, osteotomy facilitates implantation of moderately constrained prosthesis. This indication is based on CAT scan rotational deformities measurements because rotational deformities require an osteotomy, and/or the presence of extraligamentous deformity that cannot be reduced with collateral ligaments surgical release. LEVEL OF EVIDENCE: Level 4. Non-controlled retrospective study.

The impact of the mTOR inhibitor sirolimus on the proliferation and function of pancreatic islets and ductal cells.

AIMS/HYPOTHESIS: The Edmonton Protocol for islet transplantation has provided hope for type 1 diabetic patients. However, this protocol requires lifelong immunosuppression, specifically sirolimus, a cellular antiproliferate. The effect of sirolimus on human pancreatic ductal cells (HDCs) is not known. This may be important since HDCs are believed to be islet precursors. Since neonatal porcine islets (NPIs), which contain many ductal precursor cells, could be a potential clinical source of islets, we also tested the effects of sirolimus on this tissue. METHODS: HDCs (n=4), NPIs (n=9) and human islets (n=5) were cultured with and without sirolimus (20 ng/ml) for 6 days. RESULTS: HDCs and NPIs cultured with sirolimus showed a 50 and 28% decrease, respectively, in cell number relative to control (p<0.05). Control cultures expanded 1.65- and 2.44-fold relative to time 0. Decreases in cell number of sirolimus-treated HDCs were not due to apoptosis as measured by TUNEL staining. No functional effects on human islets or NPIs were observed following static incubation with high glucose. Treatment of syngeneically transplanted and naïve BALC/c mice with sirolimus resulted in altered OGTT profiles with prolonged elevation of hyperglycaemia and weight gain. There was no difference in graft and organ insulin content between treatment groups. CONCLUSIONS/INTERPRETATION: Our results indicate that sirolimus decreases ductal cell numbers in culture and alters glucose-stimulated insulin secretion in vivo. The administration of sirolimus to islet transplant recipients is likely to impair graft function as a result of decreasing ductal neogenesis and induction of insulin resistance.