Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative.

OBJECTIVES: The aetiology of bone marrow lesions (BMLs) in knee osteoarthritis (OA) is poorly understood. We employed three-dimensional (3D) active appearance modelling (AAM) to study the spatial distribution of BMLs in an OA cohort and compare this with the distribution of denuded cartilage. METHODS: Participants were selected from the Osteoarthritis Initiative progressor cohort with Kellgren-Lawrence scores ≥2, medial joint space narrowing and osteophytes. OA and ligamentous BMLs and articular cartilage were manually segmented. Bone surfaces were automatically segmented by AAM. Cartilage thickness of <0.5 mm was defined as denuded and ≥0.5-1.5 mm as severely damaged. Non-quantitative assessment and 3D population maps were used for analysing the comparative position of BMLs and damaged cartilage. RESULTS: 88 participants were included, 45 men, mean age (SD) was 61.3 (9.9) years and mean body mass index was 31.1 (4.6) kg/m(2). 227 OA and 107 ligamentous BMLs were identified in 86.4% and 73.8% of participants; OA BMLs were larger. Denuded cartilage was predominantly confined to a central region on the medial femur and tibia, and the lateral facet of the trochlear femur. 67% of BMLs were colocated with denuded cartilage and a further 21% with severe cartilage damage. In the remaining 12%, 25/28 were associated with cartilage defects. 74% of all BMLs were directly opposing (kissing) another BML across the joint. CONCLUSIONS: There was an almost exclusive relationship between the location of OA BML and cartilage denudation, which itself had a clear spatial pattern. We propose that OA, ligamentous and traumatic BMLs represent a bone response to abnormal loading.

Regional cartilage properties of three quadruped tibiofemoral joints used in musculoskeletal research studies.

Quadruped joints are commonly used in musculoskeletal studies as a surrogate for human joints despite inherent differences in tissue properties. Although concerns exist regarding model validity, relatively few studies comparing the mechanical properties of quadruped tissue exist. This study aimed to characterise the regional intrinsic mechanical properties and thickness of tibiofemoral cartilage from three quadrupeds used in modern musculoskeletal research. Osteochondral plugs were removed from the major weight-bearing regions of porcine (6 months), bovine (18-24 months) and ovine (approximately 5 years) tibiofemoral joints. The equilibrium elastic modulus and permeability of the cartilage were derived by combining the creep indention deformation results and calculated tissue thickness within an in-silica model. Results showed significant interspecies and regional variation in cartilage thickness. Cartilage was thickest on porcine femoral condyles whereas ovine cartilage was consistently thinner across all sites. Furthermore, porcine tissue had a significantly lower equilibrium elastic modulus and significantly higher permeability than ovine cartilage. The results highlight the importance of considering the interspecies and regional variation in quadruped tissue properties when selecting animal joints for musculoskeletal investigations.

The effect of bone fragment size and cerebrospinal fluid on spinal cord deformation during trauma: an ex vivo study.

OBJECT: The purpose of the study was to assess the effect of CSF and the size of the impacting bone fragment area on spinal cord deformation during trauma. METHODS: A transverse impact rig was used to produce repeated impacts on bovine and surrogate cord models. Tests were recorded with high-speed video and performed on specimens with and without CSF and/or dura mater and with 3 different impactor areas. RESULTS: The CSF layer was found to reduce the maximum cord deformation significantly. A 50% reduction in impact area significantly increased the maximum cord deformation by 20-30%. The surrogate model showed similar trends to the bovine model but with lower absolute deformation values. CONCLUSIONS: Cerebrospinal fluid protects the cord during impact by reducing its deformation. A smaller bone fragment impact area increases the deformation of the cord, in agreement with clinical results, where a higher impact energy-possibly giving rise to smaller fragments-results in a worse neurological deficit.

Inter-operator variability in pPOSSUM scores: a note of caution.

PURPOSE: Predicting perioperative morbidity and mortality can be achieved by several risk predicting algorithms. In the UK, the National Emergency Laparotomy Audit, mandated for all patients undergoing emergency laparotomy, uses pPOSSUM as its risk prediction tool. However, there is no literature reporting the inter-operator variability in calculating the score. Inter-rater variability was assessed based on 10 real general surgical cases that went on to have an emergency laparotomy. METHODS: Forty clinicians, 10 each of registrars and consultants in anaesthetics and general surgery, were asked to calculate the pPOSSUM based on the clinical information typically available at the time of making the decision to proceed to emergency laparotomy for the same 10 National Emergency Laparotomy Audit cases. All participants were surveyed to assess their understanding and use of the pPOSSUM score. RESULTS: More than 80% of respondents stated that they use pPOSSUM in daily clinical practice. There was variability in the calculated scores between the groups analysed. Two subgroups were evident: one in which the calculated mean pPOSSUM was similar between participants but did not reflect the true value, and the other which was accurate, but demonstrated high inter-rater variability. CONCLUSIONS: This is the first study to investigate inter-operator variability in pPOSSUM scores. Previous reports on the validity of the tool fail to account for subjective variation. At a time where pPOSSUM has become a routine part of clinical practice, this variability needs to be accounted for and taken into consideration in the decision-making process.

Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes.

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.