The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus NWB and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures. The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection, displacement of osteosynthesis, the full arc of ankle motion, RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay.Abstract
Objectives
Methods
Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus non-weight-bearing (NWB) and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures (lateral malleolar, bimalleolar, trimalleolar with or without syndesmotic injury). The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection (deep and superficial), displacement of osteosynthesis, the full arc of ankle motion (plantar flexion and dorsal flection), RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay.Introduction and Objective
Materials and Methods
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology. In RA, inflammation and pain are initial symptoms followed by bone and cartilage destruction. Proinflammatory cytokines play a significant role in the initiation and progress of inflammation and tissue destruction. Sensory neuropeptide substance P (SP) participates not only in nociception but also in pro-inflammatory processes by enhancing vasodilatation and recruitment of inflammatory cells. Ubiquitin proteasome system (UPS) activates a transcription factor, NF-κB which regulates the synthesis of proinflammatory mediators like cytokines; however its role in regulating pro inflammatory sensory neuropeptides is unknown. A number of proteasome inhibitors have been shown to down regulate the activity of NF-κB and hence reduce inflammation. In the present study, the effect of proteasome inhibitor (MG 132) on the severity of arthritis and pain was observed along with the expression of SP-positive nerve fibres in the ankle joint in a chronic inflammatory model of rat adjuvant arthritis. Histology and mechanical pain tests showed a significant reduction in inflammation and pain in ankle joint by daily administration of proteasome inhibitor MG132 at the dose of 1mg/kg body weight compared to untreated groups. Radiographic analysis of ankle joints indicated a reduction in soft tissue swelling and joint destruction in the treatment group. A marked reduction in the NF-κB activity was observed by EMSA. Furthermore, proteasome inhibition resulted in the normalization of up regulated neuronal response occurred during inflammation by significantly reducing the expression of SP-positive fibres in the ankle joint as demonstrated by immunohistochemistry. Our data provide the evidence that proteasome inhibitor MG132 can reduce severity of arthritis and reverse inflammatory pain behaviour by influencing the peripheral sensory nervous system. The drugs targeting UPS can be developed for treatment of chronic inflammatory joint disorders.
