Tendinopathy is the most frequent musculoskeletal disease that requires medical attention. Mechanical overload has been considered as a key driver of its pathology. However, the underline mechanism on how overload induces tendinopathy and inflammation is unclear. Extracellular mitochondria (EM) are newly identified as cell-to-cell communicators. The aim of this study is to elucidate the role of mitochondria in overload-induced inflammation. We performed three-dimensional uniaxial stretching to mouse tendon organoid in bioreactors. Cyclic strain of uniaxial loadings included underload, normal load, and overload, according to previous work. We then harvested microvesicles including EM, from the bioreactor by differential centrifugation and evaluated their characteristics by flow cytometry and super-resolution confocal microscopy. Raw 264.7 mouse macrophage cell line was used for chemotaxis assay in a Boyden Chamber System with Magnetic-Activated Cell Sorting Technology. EM induced cytokines secretion by macrophages was analyzed by a bead-based multiplex assay panel. N-Acetyl-L-cysteine (NAC) was used as the antioxidant to tendon organoid to regulate mitochondrial fitness. We showed mechanical load induced tendon organoid to release microvesicles including mitochondria. The size of microvesicles is mainly in the range from 220nm to 880nm. More than 75% of microvesicles could be stained by PKH26, confirming they were with lipophilic membrane. Super-resolution confocal microscopy identified two forms of mitochondria, including mitochondria encapsulated in vesicles and free mitochondria. Overload led to the degeneration of the organoid and induced microvesicles release containing most EM. Chemotaxis assay showed that EM from overloaded tendon organoid induced macrophages chemotaxis. In addition, microvesicles extracted from overloaded tendon organoid induced the production of proinflammatory cytokines including IL-6, KC (Keratinocyte-Derived Chemokine) and IL-18. NAC treatment to tendon cells could attenuate overload-induced macrophage chemotaxis. Overload induces EM releasing from tendon cells, which leads to chemotaxis of macrophages toward tendon, resulting in induction of inflammation.
To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population. This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015-2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence. The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 12,156 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category. Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.
Patients requiring lower limb reconstruction have often undergone significant trauma. In some patients this is a consequence of self-harm, others develop depression as a result of the accidental trauma that caused their injury. Little is known of the extent of the problem and how it changes over the course of their treatment. Patients undergoing limb reconstruction in a major trauma centre were asked to complete an online questionnaire on the day of surgery. This included a Zung self-rating depression score, LEFS and EQ5D. They were asked to complete these again at subsequent post-operative time points.Background
Design and Methods
Patients undergoing femoral lengthening by external fixation
tolerate treatment less well when compared to tibial lengthening.
Lengthening of the femur with an intramedullary device may have
advantages. We reviewed all cases of simple femoral lengthening performed
at our unit from 2009 to 2014. Cases of nonunions, concurrent deformities,
congenital limb deficiencies and lengthening with an unstable hip
were excluded, leaving 33 cases (in 22 patients; 11 patients had
bilateral procedures) for review. Healing index, implant tolerance
and complications were compared.Aims
Patients and Methods
The Exogen Ultrasound Device is licensed for fracture non-union under NICE guideline MTG-12. Reimbursement is offered if there is no fracture union after 250 days of treatment as per manufacturer guidelines. Quoted healing rates vary between 62% and 100%: we compare our results to these. A retrospective audit of all patients who received Exogen for long bone non-union was undertaken. The indication, duration of treatment, fracture outcome and compliance with the recommended treatment pathway were recorded.Background:
Method:
External fixators are not as well tolerated around the femur when compared to the tibia. Lengthening with an intramedullary device is therefore attractive. We reviewed all cases of femoral lengthening performed at our unit from 2007 to 2014. Cases of non-unions, concurrent deformities, congenital limb deficiencies and lengthening with an unstable hip were excluded. This left 33 cases for review. Healing index, implant tolerance and complications were compared.Background:
Method:
Little is known about the forces carried by the Taylor Spatial Frame (TSF) hexapod fixator. Our aim was to measure the TSF resultant force and how this changed during the consolidation phase. Five patients undergoing correction of tibial deformities were recruited. Measurements were taken at 2, 4, 8 and 12 weeks post-correction during various activities. Instrumented struts incorporating strain gauges measuring axial force were temporarily used each time. Strut forces and lengths were used to determine frame kinetics. The resultant axial fixator forces and moments were calculated relative to sitting. Ground reaction forces (GRF) were measured using the treadmill force plates.Background:
Method:
Leg length discrepancy related to absence of the femoral head with proximal migration of the femur presents a treatment dilemma. Late sequelae of neonatal hip sepsis and chronic hip dislocation due to developmental dysplasia are the most common causes. Traditional teaching dictates that the hip is stabilised prior to limb lengthening. Reconstructive options alter the shape of the proximal femur which complicates future surgery. We retrospectively reviewed 3 cases of femoral lengthening with an ‘unstable’ hip without prior stabilization. The aetiology was neonatal hip sepsis in 2 cases and chronic hip dislocation due to developmental dysplasia in 1 case. Lengthening was performed with the use of a retrograde Precice lengthening nail.Background:
Methods:
The superficial anterior vasculature of the knee is variably described; most of our information comes from anatomical literature. Descriptions commonly emphasise medial-dominant genicular branches of the popliteal artery. Quantifying the relative contribution of medial and lateral vessels to the anastomotic network of the anterior knee may help provide grounds for selecting one of a number of popular incisions for arthrotomy. To describe the relative contribution of vessels to anastomoses supplying the anterior knee.Introduction
Aim
