ABSTRACT
Osteoarthritis (OA) is a multifactorial disease contributing to significant disability and economic burden in Western populations. The aetiology of OA remains poorly understood, but is thought to involve genetic, mechanical and environmental factors. Currently, the diagnosis of OA relies predominantly on clinical assessment and plain radiographic changes long after the disease has been initiated. Recent advances suggest that there are changes in joint fluid metabolites that are associated with OA development. If this is the case, biochemical and metabolic biomarkers of OA could help determine prognosis, monitor disease progression and identify potential therapeutic targets. Moreover, for focussed management and personalised medicine, novel biomarkers could sub-stratify patients into OA phenotypes, differentiating metabolic OA from post-traumatic, age-related and genetic OA. To date, OA biomarkers have concentrated on cytokine action and protein signalling with some progress. However, these remain to be adopted into routine clinical practice. In this review, we outline the emerging metabolic links to OA pathogenesis and how an elucidation of the metabolic changes in this condition may provide future, more descriptive biomarkers to differentiate OA subtypes.
Subject(s)
Osteoarthritis , Precision Medicine , Biomarkers , Humans , Metabolomics , Osteoarthritis/diagnostic imaging , Osteoarthritis/therapy , Synovial FluidABSTRACT
OBJECTIVE: To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass spectroscopy (MS) analysis (viz., metabolomics or metabonomics), thereby providing coherent conclusions and reference material for future study. METHOD: We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1. "osteoarthritis" AND ("metabolic" OR "metabonomic" OR "metabolomic" OR "metabolism") 2. ("synovial fluid" OR "cartilage" OR "synovium" OR "serum" OR "plasma" OR "urine") AND ("NMR" or "Mass Spectroscopy"). Databases searched were "Medline" and "Embase". Studies were searched in English and excluded review articles not containing original research. Study outcomes were significant or notable metabolites, species (human or animal) and the Newcastle-Ottawa Score. RESULTS: In the 27 studies meeting the inclusion criteria, there was a shift towards anaerobic and fatty acid metabolism in OA disease, although whether this represents the inflammatory state remains unclear. Lipid structure and composition was altered within disease subclasses including phosphatidyl choline (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was described, but the correlation to disease factors was not demonstrated. Collated results suggested arachidonate signalling pathways and androgen sex hormones as future metabolic pathways for investigation. CONCLUSION: Our meta-analysis demonstrates significant small molecule differences between sample types, between species (such as human and bovine), with potential OA biomarkers and targets for local or systemic therapies. Studies were limited by numbers and a lack of disease correlation. Future studies should use NMR and MS analysis to further investigate large population subgroups including inflammatory arthropathy, OA subclasses, age and joint differences.
Subject(s)
Cartilage/metabolism , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Metabolomics/methods , Osteoarthritis/metabolism , Animals , Biomarkers/metabolism , Cartilage/diagnostic imaging , Humans , Osteoarthritis/diagnosis , Synovial Membrane/diagnostic imaging , Synovial Membrane/metabolismABSTRACT
INTRODUCTION: An ABC priority driven approach to the management of high energy pelvic injuries has been developed and applied as a teaching tool. A prospective study assessed whether trainees taught this ABC aide memoire gave better priority driven care in simulated patient scenarios. They were compared directly to colleagues undergoing the same pelvic training but without reference to the ABC concept. METHODS: Orthopaedic trainees were formally assessed by viva scenario upon their pelvic trauma management 6 weeks after a pelvic trauma teaching event. Trainees all received standard pelvic trauma teaching but were randomised into two groups. One group alone had an introduction to the ABC algorithm. Inclusion criteria were trainees belonging to the same deanery teaching group with similar levels of training and experience in pelvic trauma. Those completing a pelvic trauma post or teaching in pelvic trauma were excluded. RESULTS: There were 20 trainees included and three scenarios giving 60 scores. The mean year of training or the number of pelvic trauma cases experienced did not differ significantly between the groups (p=0.426 and p=0.347). The ABC teaching concept yielded significant improvements in several aspects: coagulopathy assessment and management (p=<0.001); urological injury (p=0.047), appropriate prioritisation (p=0.006) and bowel injury/open fracture assessment (p=0.007). A poorer response was seen in CT assessment (p=0.004). DISCUSSION AND CONCLUSION: The ABC priority driven approach to pelvic trauma management provides structure when decision making. This method improves clinician's recall, prioritisation and potentially clinical outcomes.
Subject(s)
Decision Support Techniques , Emergency Medicine/education , Patient Simulation , Pelvic Bones/diagnostic imaging , Quality Improvement/organization & administration , Quality of Health Care/organization & administration , Trauma Centers/organization & administration , Abbreviations as Topic , Clinical Competence , Decision Making , Humans , Pelvic Bones/injuries , Program Evaluation , Prospective Studies , Radiography , United KingdomABSTRACT
OBJECTIVE: We report a case of familial medullary thyroid carcinoma in an 87-year-old woman, despite the patient having a high-risk codon 620 mutation. METHOD: Medline and PubMed were searched for cases and literature reviews relating to the following keywords: 'codon 620', 'medullary thyroid carcinoma', 'multiple endocrine neoplasia' and 'RET proto-oncogene'. RESULTS: We report the case of an 87-year-old woman who presented with a goitre, later identified as medullary thyroid carcinoma. Genetic analysis revealed a RET proto-oncogene codon 620 mutation. Genetic testing has revolutionised the management of medullary thyroid carcinoma. The genetic basis of hereditary medullary thyroid carcinoma lies with the RET proto-oncogene. Several disease-causing mutations of this gene have been identified and their clinical prognosis described. The penetrance of these mutations is high; as such, carriers progress to develop medullary thyroid carcinoma at a young age. Mutations at the codon 620 position are classified as high-risk for early development of medullary thyroid carcinoma; thus, the current recommendation is for prophylactic thyroidectomy at five years of age. CONCLUSIONS: In this case, the progress of hereditary medullary thyroid carcinoma was unique, considering the late presentation of medullary thyroid carcinoma despite the presence of the high-risk RET proto-oncogene codon 620 mutation. The authors wish to highlight the importance of this case, as it may present a counter-argument to the current recommendations for early, prophylactic thyroidectomy in codon 620 mutation carriers in order to prevent early development of medullary thyroid carcinoma.