Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7 | 3 |
Abstract | 3 |
Introduction | 3 |
Results | 4 |
Excessive mechanical loading induces chondrocyte senescence in vitro and in mice | 4 |
Chondrocyte FBXW7 is reduced by mechanical overloading and is decreased in articular cartilage of patients with OA, aged mice and OA mice | 4 |
FBXW7 deletion in chondrocytes accelerates cartilage ageing and exacerbates OA development in mice | 7 |
FBXW7 overexpression in cartilage alleviates OA development | 7 |
FBXW7 loss by excessive mechanical loading activates MKK7–JNK signalling to promote chondrocyte senescence | 7 |
Inhibition of MKK7–JNK signalling delays chondrocyte senescence and OA development | 8 |
Discussion | 8 |
References | 12 |
Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial | 14 |
Abstract | 14 |
Introduction | 14 |
Methods | 15 |
Study design and patients | 15 |
Patient and public involvement | 15 |
Randomisation and masking | 15 |
Procedures | 15 |
Outcomes | 15 |
Statistical analysis | 16 |
Results | 16 |
Patients | 16 |
Primary and secondary outcomes | 16 |
Safety | 17 |
Sensitivity analyses | 17 |
Discussion | 18 |
References | 19 |
Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases | 21 |
Abstract | 21 |
Introduction | 21 |
Methods | 22 |
Design | 22 |
Study population | 22 |
Vaccination procedure | 22 |
Assessment of humoral responses | 22 |
Assessment of cellular CD4 and CD8 responses | 22 |
Statistical analysis | 23 |
Results | 23 |
Demographic characteristics | 23 |
Immunogenicity of mRNA vaccines in patients with IMRD | 23 |
Effect of different immunotherapies on the immunogenicity of the vaccine in patients with IMRD | 24 |
Humoral response | 24 |
Cellular responses | 26 |
Multivariate analysis | 26 |
Discussion | 26 |
References | 28 |
Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease | 29 |
Abstract | 29 |
Introduction | 29 |
Methods | 30 |
Study design | 30 |
Receptor occupancy assay | 30 |
PK, IgG and autoantibody quantification | 31 |
Immune profiling | 31 |
Results | 31 |
Patient demographics | 31 |
Safety | 31 |
Efficacy | 32 |
Pharmacokinetics and pharmacodynamics | 33 |
Downstream pharmacology of targeting CD38 | 36 |
Cytometry by time of flight | 36 |
IFN gene signature | 36 |
Discussion | 36 |
References | 38 |
First use of tofacitinib to treat an immune checkpoint inhibitor-induced arthritis | 39 |
Summary | 39 |
Background | 39 |
Case presentation | 39 |
Investigations | 39 |
Single cell synovial tissue analysis | 40 |
Treatment | 41 |
Outcome and follow-up | 41 |
Discussion | 42 |
References | 43 |
Reactive arthritis after COVID-19 | 44 |
Summary | 44 |
Background | 44 |
Case presentation | 44 |
Investigations | 44 |
Differential diagnosis | 45 |
Treatment | 45 |
Outcome and follow-up | 45 |
Discussion | 45 |
References | 46 |
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