BackgroundIn past decades, treatment of rheumatoid arthritis (RA) has advanced greatly, driven largely by the advent of new medications and treat-to-target (T2T) strategy, but the secular trends in the activity and remission of RA over past years and the efficacy of T2T strategy are not fully validated in large population in real life practice.Objectives:To investigate the trends in the activity of RA over past 8 years and evaluate the value of T2T strategy in daily practice.Methods:All the medical records of RA patients from 2009 to 2016 were retrospectively reviewed. Disease activity scores at obtained visits were measured by DAS28-CRP, DAS28-ESR, SDAI and CDAI. To display trends over years, both mean and time-adjusted methods were applied in calculation of annual disease activity and remission rate. Disease activity and remission rate were also compared before and after the year of 2011 when application of T2T strategy was initiated in our center. Furthermore, a sub-cohort study including T2T and non-T2T period groups was conducted with outcome of cumulative percentage of remission and time to achieve first remission during the first year follow-up.Results:In total, 1,001 patients with 6,944 clinical visits were included. Over eight-year period, significant improvements were witnessed in disease activity and remission rate, measured by all four indices (p<0.0001). More patients achieved lower disease activity and higher remission rates after T2T adherence in 2011 compared to those in the years of 2009 and 2010 (P<0.0001). Moreover, sub-cohort study revealed that more patients (49.3%>73.2% vs. 19.1%>34.5%, OR=2.4-3.0) achieved remission with a shorter median time compared with the non-T2T period group (p<0.0001), particularly in DAS28-CRP (21 vs. >52 weeks), DAS28-ESR (37 vs. >52 weeks).Figure 1 Trends in disease activity scores over 8 years by four indices in mean and adjusted mean (AM) methods. (A) Trends based on DAS28-CRP and DAS28-ESR in two methods (B) Trends based on SDAI and CDAI in two methodsConclusions:Over past 8 years, the RA activity has substantially decreased and T2T strategy was directly attributable to the favorable changes in clinical practice.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010;376:1094-108.[2] Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomized controlled trial. Lancet 2004;364(9430):263-9.[3] Verstappen SM, Jacobs JW, van der Veen MJ, Heurkens AH, Schenk Y, ter Borg EJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007;66(11):1443-9.[4] Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Kerstens PJ, et al. DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis. Ann Rheum Dis 2010;69(1):65-9.Acknowledgements:We wou...

Background and purpose Dermatomyositis (DM) with anti‐nuclear matrix protein‐2 (NXP‐2) antibodies usually shows multifocal ischaemic lesions in muscle. Here, we aimed to investigate the microarteriopathy underlying muscle ischaemia in anti‐NXP‐2‐positive DM. Methods A total of 16 patients diagnosed with anti‐NXP‐2‐positive DM were investigated by muscle biopsy. A total of 13 patients with DM with other myositis‐specific antibodies and 11 normal controls were included for comparison. Immunofluorescence assays were performed to localize endothelial cells, smooth muscle cells and pericytes, and to determine lesions in myofibers and microvessels by vascular endothelial growth factor and myxovirus resistance protein A (MxA). Electron microscopy was carried out to assess ultrastructure alterations. Results Subcutaneous edema, severe muscle weakness and dysphagia together with elevated creatine kinase, D‐dimer and triglyceride levels, and decreased albumin levels were found in anti‐NXP‐2‐positive DM. Muscle ischaemia included regional muscle edema, perifascicular atrophy, microinfarcts and focal punched‐out vacuoles. The density of arterioles was higher in anti‐NXP‐2‐positive DM (P ＜ 0.05). Perimysial arterioles with thickened vascular wall, thrombosis and lipid accumulation were found in the vascular wall of diseased perimysial arterioles. The frequency of diseased arterioles and thrombosis was higher in anti‐NXP‐2‐positive DM (P < 0.05). Sarcoplasmic vascular endothelial growth factor and MxA expression was observed in multifocal ischaemic lesions. MxA was present in endothelial and smooth muscle cells of the diseased arterioles and pericytes. Electron microscopy confirmed damaged capillaries and tubuloreticular structures. Conclusions Our research suggested that perimysial arterioles were most commonly involved in anti‐NXP‐2‐positive DM, which led to muscle ischaemia.

Hearing loss is one of the most common sensory disorders worldwide, and about half of all occurrences are attributable to genetic factors. Here, we have identified a novel pathogenic variant in HOMER2 in a Chinese family with autosomal dominant, non-syndromic hearing loss. This is the second family reported globally with hearing loss caused by a variant in HOMER2. The pathogenic variant c.840_841insC in HOMER2 (NM_199330), segregating with the hearing-loss phenotype in the family, leads to a premature stop codon producing a truncated protein. The coiled-coil domain in the C-terminal of HOMER2 protein is essential for protein multimerization and HOMER2-CDC42 interaction. We compared the phenotypes in the two families and found that hearing impairment in this Chinese family was more severe. Furthermore, we found that the ability of this insertion mutant type HOMER2 (HOMER2 ) to multimerize decreased more significantly than wild-type HOMER2 (HOMER2 ) and the reported c.554G>C (NM_004839) mutant HOMER2. HOMER2 protein tended to be distributed in a diffuse manner, whereas HOMER2 and the reported mutant HOMER2 tended to cluster together. Our research provides a validating second family for variants in HOMER2 causing non-syndromic sensorineural hearing loss. HOMER2 homo-/hetero-multimerization might be the first step in exerting its normal function.

No abstract

No abstract