Centre for Experimental Medicine and Rheumatology (EMR)
https://qmro.qmul.ac.uk/xmlui/handle/123456789/32483
2024-03-28T21:53:34ZMolecular portrait of chronic joint diseases: Defining endotypes toward personalized medicine.
https://qmro.qmul.ac.uk/xmlui/handle/123456789/95784
Molecular portrait of chronic joint diseases: Defining endotypes toward personalized medicine.
Ghirardi, GM; Delrosso, CA; Nerviani, A; Boutet, M-A
Joint diseases affect hundreds of millions of people worldwide, and their prevalence is constantly increasing. To date, despite recent advances in the development of therapeutic options for most rheumatic conditions, a significant proportion of patients still lack efficient disease management, considerably impacting their quality of life. Through the spectrum of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) as quintessential and common rheumatic diseases, this review first provides an overview of their epidemiological and clinical features before exploring how the better definition of clinical phenotypes has helped their clinical management. It then discusses the recent progress in understanding the diversity of endotypes underlying disease phenotypes. Finally, this review highlights the current challenges of implementing molecular endotypes towards the personalized management of RA, PsA and OA patients in the future.
2024-01-19T00:00:00ZAxl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.
https://qmro.qmul.ac.uk/xmlui/handle/123456789/95783
Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.
Nerviani, A; Boutet, M-A; Ghirardi, GM; Goldmann, K; Sciacca, E; Rivellese, F; Pontarini, E; Prediletto, E; Abatecola, F; Caliste, M; Pagani, S; Mauro, D; Bellan, M; Cubuk, C; Lau, R; Church, SE; Hudson, BM; Humby, F; Bombardieri, M; Lewis, MJ; Pitzalis, C
The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment.
2024-03-16T00:00:00ZExercise therapy for tendinopathy: a mixed-methods evidence synthesis exploring feasibility, acceptability and effectiveness.
https://qmro.qmul.ac.uk/xmlui/handle/123456789/95290
Exercise therapy for tendinopathy: a mixed-methods evidence synthesis exploring feasibility, acceptability and effectiveness.
Cooper, K; Alexander, L; Brandie, D; Brown, VT; Greig, L; Harrison, I; MacLean, C; Mitchell, L; Morrissey, D; Moss, RA; Parkinson, E; Pavlova, AV; Shim, J; Swinton, PA
BACKGROUND: Tendinopathy is a common, painful and functionally limiting condition, primarily managed conservatively using exercise therapy. REVIEW QUESTIONS: (i) What exercise interventions have been reported in the literature for which tendinopathies? (ii) What outcomes have been reported in studies investigating exercise interventions for tendinopathy? (iii) Which exercise interventions are most effective across all tendinopathies? (iv) Does type/location of tendinopathy or other specific covariates affect which are the most effective exercise therapies? (v) How feasible and acceptable are exercise interventions for tendinopathies? METHODS: A scoping review mapped exercise interventions for tendinopathies and outcomes reported to date (questions i and ii). Thereafter, two contingent systematic review workstreams were conducted. The first investigated a large number of studies and was split into three efficacy reviews that quantified and compared efficacy across different interventions (question iii), and investigated the influence of a range of potential moderators (question iv). The second was a convergent segregated mixed-method review (question v). Searches for studies published from 1998 were conducted in library databases (n = 9), trial registries (n = 6), grey literature databases (n = 5) and Google Scholar. Scoping review searches were completed on 28 April 2020 with efficacy and mixed-method search updates conducted on 19 January 2021 and 29 March 2021. RESULTS: Scoping review - 555 included studies identified a range of exercise interventions and outcomes across a range of tendinopathies, most commonly Achilles, patellar, lateral elbow and rotator cuff-related shoulder pain. Strengthening exercise was most common, with flexibility exercise used primarily in the upper limb. Disability was the most common outcome measured in Achilles, patellar and rotator cuff-related shoulder pain; physical function capacity was most common in lateral elbow tendinopathy. Efficacy reviews - 204 studies provided evidence that exercise therapy is safe and beneficial, and that patients are generally satisfied with treatment outcome and perceive the improvement to be substantial. In the context of generally low and very low-quality evidence, results identified that: (1) the shoulder may benefit more from flexibility (effect sizeResistance:Flexibility = 0.18 [95% CrI 0.07 to 0.29]) and proprioception (effect sizeResistance:Proprioception = 0.16 [95% CrI -1.8 to 0.32]); (2) when performing strengthening exercise it may be most beneficial to combine concentric and eccentric modes (effect sizeEccentricOnly:Concentric+Eccentric = 0.48 [95% CrI -0.13 to 1.1]; and (3) exercise may be most beneficial when combined with another conservative modality (e.g. injection or electro-therapy increasing effect size by ≈0.1 to 0.3). Mixed-method review - 94 studies (11 qualitative) provided evidence that exercise interventions for tendinopathy can largely be considered feasible and acceptable, and that several important factors should be considered when prescribing exercise for tendinopathy, including an awareness of potential barriers to and facilitators of engaging with exercise, patients' and providers' prior experience and beliefs, and the importance of patient education, self-management and the patient-healthcare professional relationship. LIMITATIONS: Despite a large body of literature on exercise for tendinopathy, there are methodological and reporting limitations that influenced the recommendations that could be made. CONCLUSION: The findings provide some support for the use of exercise combined with another conservative modality; flexibility and proprioception exercise for the shoulder; and a combination of eccentric and concentric strengthening exercise across tendinopathies. However, the findings must be interpreted within the context of the quality of the available evidence. FUTURE WORK: There is an urgent need for high-quality efficacy, effectiveness, cost-effectiveness and qualitative research that is adequately reported, using common terminology, definitions and outcomes. STUDY REGISTRATION: This project is registered as DOI: 10.11124/JBIES-20-00175 (scoping review); PROSPERO CRD 42020168187 (efficacy reviews); https://osf.io/preprints/sportrxiv/y7sk6/ (efficacy review 1); https://osf.io/preprints/sportrxiv/eyxgk/ (efficacy review 2); https://osf.io/preprints/sportrxiv/mx5pv/ (efficacy review 3); PROSPERO CRD42020164641 (mixed-method review). FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) HTA programme and will be published in full in HTA Journal; Vol. 27, No. 24. See the NIHR Journals Library website for further project information.
2023-10-01T00:00:00Z193 Can we predict the outcome for recovery of plantar heel pain? An international prospective cohort study
https://qmro.qmul.ac.uk/xmlui/handle/123456789/95242
193 Can we predict the outcome for recovery of plantar heel pain? An international prospective cohort study
Gulle, H; Prior, T; Miller, S; Birn-Jeffery, A; Morrissey, D; Abstracts
2022-02-01T00:00:00Z