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  • Osteoarthritis biomarkers: year in review.

    28 June 2018

    OBJECTIVE: To summarise important findings from biomarker studies relevant to osteoarthritis (OA), published between April 2016 and March 2017; to consider these findings in the context of new discoveries and technologies, and clinical and scientific need in OA. DESIGN: Studies were selected by PubMed search, conducted between 01/04/2016 and 01/03/2017. MeSH terms [biomarker] AND [OA] were used; the search was restricted to Human, English language and Full Text Available publications, which yielded 50 eligible publications. Any biomarker was considered, including non-proteins and other clinical measurements. RESULTS: Three main areas are overviewed: 1) Studies examining highly validated biomarkers, in the FNIH OA Biomarkers Consortium and elsewhere, particularly their ongoing application and validation. Control reference intervals, work on predictive validity and other longitudinal studies examining prognostic value of biomarkers in large cohorts are reviewed. 2) Novel studies relating to biomarkers of inflammation are discussed, including complement, the performance of markers of so-called 'cold inflammation' and results from clinical trials including biomarkers. 3) Discovery studies, including whole blood RNA, proteomics and metabolomics are reviewed, with an emphasis on new technologies. CONCLUSIONS: Discovery, characterisation and qualification of various biomarkers is ongoing; several novel protein and non-protein candidate biomarkers have been reported this year. Biomarkers provide us with an opportunity to better diagnose and stratify the disease, via established panels or new discovery approaches. Improving quality of sampling and testing, and measuring large numbers of markers simultaneously in large cohorts would seem likely to identify new clinically applicable biomarkers, which are still much needed in this disease.

  • The Role of Metabolite-Sensing G Protein-Coupled Receptors in Inflammation and Metabolic Disease.

    3 July 2018

    SIGNIFICANCE: Great attention has been placed on the link between metabolism and immune function giving rise to the term "immunometabolism." It is widely accepted that inflammation and oxidative stress are key processes that underlie metabolic complications during obesity, diabetes, and atherosclerosis. Therefore, identifying the mechanisms and mediators that are involved in the regulation of both inflammation and metabolic homeostasis is of high scientific and therapeutic interest. Recent Advances: G protein-coupled receptors (GPCRs) that signal in response to metabolites have emerged as attractive therapeutic targets in inflammatory disease. Critical Issues and Future Directions: In this review, we discuss recent findings about the physiological role of the main metabolite-sensing GPCRs, their implication in immunometabolic disorders, their principal endogenous and synthetic ligands, and their potential as drug targets in inflammation and metabolic disease. Antioxid. Redox Signal. 29, 237-256.

  • International variation in shoulder arthroplasty.

    3 July 2018

    Background and purpose - The number of shoulder registries increases. We assessed international trends in use of shoulder arthroplasty, and described the current state of procedure selection and outcome presentation as documented in national and regional joint registries. Methods - Published reports from 9 population-based shoulder arthroplasty registries (country/region: Norway, Sweden, New Zealand, Denmark, California, Australia, Emilia-Romagna, Germany, and United Kingdom) were analyzed. Data were extracted on age, sex, disease indication, type of surgical procedure, surgical volume, and outcomes. Results - Shoulder arthroplasty incidence rate in 2012 was 20 procedures/105 population with a 6-fold variation between the highest (Germany) and lowest (United Kingdom) country. The annual incidence rate increased 2.8-fold in the past decade. Within the indications osteoarthritis, fracture, and cuff-tear arthropathy variations in procedure choice between registries were large. Outcomes evaluation focused on revision in all registries, but different measures and strata were used. Only Australia provided revision rates for prosthesis brands stratified by both indication and procedure. Finally, in 2 registries with available data surgeons performed on average 10-11 procedures yearly. Interpretation - Annual incidence rates of shoulder arthroplasty have almost tripled over the past decade. There is wide variation in procedure selection for the major indications, a low average surgeon volume, a substantial number of brands with small annual volume, and large variation in outcome presentation. The internationally increasing registry activity is an excellent basis for improving the so far weak evidence in shoulder arthroplasty.

  • Incidence of shoulder dislocations in the UK, 1995-2015: a population-based cohort study.

    3 October 2018

    OBJECTIVE: This cohort study evaluates the unknown age-specific and gender-specific incidence of primary shoulder dislocations in the UK. SETTING: UK primary care data from the Clinical Practice Research Datalink (CPRD) were used to identify patients aged 16-70 years with a shoulder dislocation during 1995-2015. Coding of primary shoulder dislocations was validated using the CPRD general practitioner questionnaire service. PARTICIPANTS: A cohort of 16 763 patients with shoulder dislocation aged 16-70 years during 1995-2015 were identified. PRIMARY OUTCOME MEASURE: Incidence rates per 100 000 person-years and 95% CIs were calculated. RESULTS: Correct coding of shoulder dislocation within CPRD was 89% (95% CI 83% to 95%), and confirmation that the dislocation was a 'primary' was 76% (95% CI 67% to 85%). Seventy-two percent of shoulder dislocations occurred in men. The overall incidence rate in men was 40.4 per 100 000 person-years (95% CI 40.4 to 40.4), and in women was 15.5 per 100 000 person-years (95% CI 15.5 to 15.5). The highest incidence was observed in men aged 16-20 years (80.5 per 100 000 person-years; 95% CI 80.5 to 80.6). Incidence in women increased with age to a peak of 28.6 per 100 000 person-years among those aged 61-70 years. CONCLUSIONS: This is the first time the incidence of shoulder dislocations has been studied using primary care data from a national database, and the first time the results for the UK have been produced. While most primary dislocations occurred in young men, an unexpected finding was that the incidence increased in women aged over 50 years, but not in men. The reasons for this are unknown. Further work is commissioned by the National Institute for Health Research to examine treatments and predictors for recurrent shoulder dislocation. STUDY REGISTRATION: The design of this study was approved by the Independent Scientific Advisory Committee (15_260) for the Medicines & Healthcare products Regulatory Agency.

  • Foxp3+ T reg cells control psoriasiform inflammation by restraining an IFN-I-driven CD8+ T cell response.

    13 August 2018

    Psoriasis is a complex inflammatory skin disease affecting ∼3% of the population worldwide. Although type I interferons (IFN-I) are thought to be involved in its pathogenesis, the details of this relationship remain elusive. Here we show that in a murine model of imiquimod-driven psoriatic skin inflammation, Foxp3+ regulatory T cells (T reg cells) control inflammation severity by restraining IFN-I. Depletion of T reg cells induces IFN-I and IFN-stimulated gene expression, and leads to accumulation of CD8+ T cells in lesional skin. Mononuclear phagocytes (MNPs) were the source of IFN-I, and their depletion reversed the effect of T reg cell depletion. Blockade of IFN-I signaling abolished CD8+ T cell infiltration and excess inflammation in the skin of T reg cell-depleted mice. Depletion of CD8+ T cells attenuated pathology, confirming their role as critical effector cells downstream of IFN-I. Our results describe an unexpected role for T reg cells in restraint of an MNP-IFN-I-driven CD8+ T cell response during psoriasiform skin inflammation. These findings highlight a pathway with potential relevance for the treatment of early-stage disease.