Difficult-to-treat rheumatoid arthritis (D2T-RA) is defined by poor treatment responses to multiple biological or targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs). The factors underlying treatment failure in patients with D2T-RA are poorly understood and likely multi-factorial. It is well established that poor medication adherence, defined as the extent to which a patient takes medication as prescribed by their healthcare professional, can diminish the therapeutic response. This can result in unremitting disease activity leading to recurrent cycling of b/tsDMARDs. Herein, we performed a systematic literature review to examine the proportion of b/tsDMARD adherence, by measures of drug implementation, within a refractory RA population. Six databases (Medline, PubMed, Embase, CINAHL, PsycINFO and Cochrane Library databases) spanning from 1990 to October 2023 were searched for RA studies in relation to adherence to b/tsDMARDs. Studies were required to be observational and consist exclusively of refractory RA patients, defined as those with ≥1 previous b/tsDMARD and meeting the 1987 ACR and/or 2010 ACR/EULAR and/or the International Classification of Diseases classification for RA. Subsequent study selection and extraction were performed independently by two investigators according to strict criteria. Adherence outcomes were respective of drug implementation calculated using medication possession ratio and/or proportion of days covered. Results were extracted to show the percentage of patients deemed adherent according to the individual study criteria. A total of 2091 records were identified from the systematic search, of which six studies were eligible and available for extraction. Study cohorts included data from a total of 22,363 exclusively biologic-experienced RA patients, originating from the USA in five studies, and from Spain in the remaining study. Five studies examined adherence to a combination of anti-TNFα and non-TNFα inhibiting agents, with the remaining study examining anti-TNFα drugs only. Three studies reported the proportion of adherent patients to all b/tsDMARDs as ranging between 38.3% to 89.2%. The proportion of adherent patients to various individual anti-TNFα agents ranged between 19% to 55.3% amongst five studies, and between 29.5% to 54.3% for non-TNFα inhibitors in four studies. This systematic review suggests that in refractory patients, b/tsDMARDs adherence remains sub-optimal following drug switching and this remains true for both anti-TNFα and non-TNFα inhibiting agents. This could contribute to poor treatment outcomes and unwarranted drug cycling. Further surveillance of the factors leading to, and characteristics associated with poor treatment adherence will be important in deciding future interventions to improve medication adherence and subsequent treatment outcomes in this population. R. Singh: None. R. Choudhury: None. E. Butt: None. A.P. Croft: None.

The role of fibroblasts in determining tissue topography and immune cell organisation within chronically inflamed tissues is poorly understood. Herein, we use multi-omic spatial analysis to define the cellular zonation pattern of the synovium in patients with inflammatory arthritis, identifying discrete tissue niches underpinned by spatially programmed subsets of synovial fibroblasts. We observe that perivascular fibroblasts switch on distinct matrix programs in response to cytokine signalling from neighbouring cells, forming adapted tissue niches that either permit or restrict immune cell trafficking. Specifically, IFN-gamma responsive fibroblasts form a pathogenic lymphocyte-permissive niche that supports the persistence of leukocytes in the tissue, whilst TGF-beta responsive, matrix-synthesising fibroblasts comprise a reparative niche, composed of a collagen-rich barrier around blood vessels that restricts leukocyte migration and promotes resolution of tissue inflammation. Augmentation of such endogenous pathways to promote resolution of inflammation may offer therapeutically tractable approaches for restoration of tissue homeostasis. ### Competing Interest Statement The authors have declared no competing interest.

Background/Aims Estimates predict between 10-20% of RA patients meet difficult-to-treat Rheumatoid Arthritis (D2T-RA) classification, representing a clinically distinct cohort. There is a significant unmet need in the identification and management of these patients. Discerning significant characteristics across cohorts may identify predictors for D2T-RA, which may prompt earlier clinical recognition and patient-tailored, holistic management to improve clinical outcomes. This review aims to describe the clinical characteristics of patients with EULAR-defined D2T-RA to help identify and manage predictors, contributory factors, or consequences of difficult-to-treat disease. Methods A systematic literature search of PubMed, Embase and Web of Science databases for studies pertaining to characteristics of D2T-RA was undertaken from database inception to May 2023. Results were screened against strict inclusion/exclusion criteria. Risk-of-bias (RoB) assessments were performed using the Newcastle-Ottawa Scale (NOS) and a modified version for cross-sectional studies (mNOS). Significant (p < 0.05) baseline characteristics between D2T-RA and non-D2T patients were extracted for comparison following thematic analysis. Where there was conflict in the direction of the extracted characteristics; the number and quality of studies were used to resolve evidential disagreements. Results 1687 studies were identified, of which seven fulfilled the inclusion criteria. Included studies were observational, published between 2021 and 2023, with mean D2T and non-D2T sample sizes of 83 and 417 patients, respectively. Five of the seven cohorts were European, with two from Japan. Following RoB and dispute resolution, all seven identified studies were included for analysis. Key themes elucidated are shown in table 1. Of note, significant characteristics included female sex, autoantibody positivity, greater annual bone erosion progression, interstitial lung disease, mental health conditions, and non-adherence. Conclusion Greater awareness of clinical characteristics of D2T-RA patients will assist clinicians by promoting the assessment of traits associated with poor treatment response. This is the first review to systematically describe characteristics of D2T-RA patients across multiple cohorts. Several commonly recorded, modifiable characteristics were associated with D2T-RA. Evidential disagreements and heterogeneous study designs were analytical barriers, and clinical intervention studies are needed to determine if addressing these factors in the routine clinical setting improves clinical outcomes and prevention in D2T-RA.

Abstract Background Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. Results Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs. Conclusions Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

Despite recent advances with the introduction of biologic/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs); there is a growing number of individuals with rheumatoid arthritis (RA) in whom stepwise escalation of current treatment modalities remain ineffective1. Improvement in disease activity can be impacted by inflammatory and non-inflammatory components, and thus improving outcomes in this cohort of patients relies on holistic care. Recently, the European Alliance of Associations for Rheumatology (EULAR) defined this subset of RA patients as 'Difficult-to-treat' (D2T-RA), whereby there is failure of ≥2 b/tsDMARDs classes with signs/symptoms of disease activity or burden2. D2T-RA represents a significant area of clinical unmet need in the NHS, consisting of individuals with complex needs. Herein, we looked at identifying the presence of non-inflammatory aspects of D2T-RA in a real-world cohort; with the objective of providing justification for the development of a novel multidisciplinary clinic through which we can approach and address the needs of patients with D2T-RA. RA patients aged ≥18 who had failed two or more classes of b/tsDMARDs were identified and recruited from two centres. Clinical, demographic, and serological data were collected at baseline. Responses were collected to questionnaires including: fulfilment of fibromyalgia classification criteria, Patient Health Questionnaire-9 (PHQ-9), Brief Illness Perception Questionnaire (B-IPQ), Beliefs about Medicines Questionnaire-Specific (BMQ-S), fatigue visual analogue scores (VAS) and Medication Adherence Report Scale-5 (MARS-5). A total of 19 patients fulfilling EULAR defined D2T-RA criteria were recruited. Patient, disease and outcome characteristics are summarised in Table 1. In brief, 90% were female and 90% were anti-CCP positive. Median BMI was raised at 25.8, and median disease activity scores reflected moderate disease. Four patients were classified as having co-existing fibromyalgia. Median PHQ-9 and VAS scores reflect a mild level of depressive illness and high level of self-reported fatigue respectively. Ever-non adherence (classified as a response other than 'never' within the MARS-5 questionnaire) was noted in 47% and 37% of the cohort in regards to csDMARDs and b/tsDMARDS respectively - despite an overall accepting view of treatment based on the positive necessity-concerns differential (NCD). In conjunction with advances in biologic therapies, treatment stratification and early intervention; management of non-inflammatory factors is likely to provide benefit to the D2T-RA cohort. Our results show that factors such as increased BMI, depression, fatigue, non-adherence, fibromyalgia, and a negative view of illness are present in a population of D2T-RA patients. These can impact on treatment response and patient outcomes. The creation of a dedicated, robust, multi-disciplinary clinic, aimed at identification, targeted management and follow-up of these potentially modifiable factors could prove valuable in managing this complex group of patients.

Objective Early treatment of RA improves clinical outcomes; however, the impact on health economic outcomes is unclear. This review sought to investigate the relationship between symptom/disease duration and resource utilization/costs and the responsiveness of costs following RA diagnosis. Methods A systematic search was performed on Pubmed, EMBASE, CINAHL and Medline. Studies were eligible if patients were DMARD-naive and fulfilled 1987 ACR or 2010 ACR/EULAR RA classification criteria. Studies had to report symptom/disease duration and resource utilization or direct/indirect costs as health economic outcomes. The relationships between symptom/disease duration and costs were explored. Results Three hundred and fifty-seven records were identified in a systematic search; nine were eligible for analysis. The mean/median of symptom/disease duration in studies ranged between 25 days and 6 years. Annual direct costs of RA following diagnosis showed a U-shaped distribution in two studies. Longer symptom duration before starting a DMARD (>180 days) was associated with lower health-care utilization in the first year of RA diagnosis in one study. Annual direct and indirect costs 6 months before RA diagnosis were higher in patients with shorter symptom duration (<6 months) in one study. Given the clinical and methodological heterogeneities, the association between symptom/disease duration and costs after diagnosis was not computed. Conclusion The association between symptom/disease duration at the time of DMARD initiation and resource utilization/cost in patients with RA remains unclear. Health economic modelling with clearly defined symptom duration, resource utilization and long-term productivity is vital to address this evidence gap. Lay Summary What does this mean for patients? We studied the extent to which the cost of health care varies depending on how quickly patients with rheumatoid arthritis (RA) receive treatment after diagnosis. This is important to allow long-term financial planning within the health-care service. This is a systematic review study, which means we collect information from published papers that meet a set of criteria to see whether there is a clear pattern emerging across multiple papers. In this study, we selected papers that included patients with a diagnosis of RA and with no previous treatment for their RA. We then studied whether there is any clear link between the delay in starting treatment for RA and costs of treating RA. In two selected studies, the costs of RA treatment (e.g. medication costs, consultation costs) showed a U-shaped distribution; that means costs were high in the initial years after starting treatment, then dropped before subsequently rising again. It was not possible to assess further whether there is a clear link between the delay in starting treatment for RA and costs of treating RA, because each study used different criteria to assess treatment delay and costs of treatment. Therefore, this study highlights that there is a need for further economic modelling studies in RA.

This is a correction to: Ilfita Sahbudin, Ruchir Singh, Paola De Pablo, Elizabeth Rankin, Benjamin Rhodes, Elizabeth Justice, Emma Derrett-Smith, Nicole Amft, Nehal Narayan, Catherine McGrath, Sangeetha Baskar, Jeanette Trickey, Mark Maybury, Karim Raza, Andrew Filer, The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persistent arthritis, Rheumatology, 2022, keac199, https://doi.org/10.1093/rheumatology/keac199 In the originally published version of this manuscript, there was an error in the eleventh author’s surname. The eleventh author’s surname should read “Baskar” instead of “Baskhar”.

Abstract Background/Aims Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), functioning, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) and RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in 838 patients with CSA, UA or RA recruited to the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F, respectively. Descriptive statistics and multivariate linear regression were performed to assess associations between clinical/demographic variables and PROMs. Results Patients with RA at initial presentation had worse PROMs than those with CSA or UA. However, HRQoL was decreased in all groups. In patients with CSA/UA, HRQoL was comparable to data relating to chronic conditions such as heart failure, severe COPD or mild angina from the Health Survey for England (HSE). Associations between predictor variables and PROMs are summarised in Table 1. Increased functional disability was associated with female sex, older age, obesity, lower quintiles of social deprivation, increased disease activity and polypharmacy. HRQoL was associated with increased disease activity and polypharmacy. The severity of depression (PHQ-9) increased with older age, increasing BMI, living in areas with the lowest quintile of social deprivation, increased disease activity and polypharmacy. Fatigue (FACIT-F) was associated with female sex, increasing BMI, disease activity and polypharmacy. After adjusting for the demographic and clinical factors, the diagnosis assigned at baseline did not affect any of the studied PROMs, but disease activity and polypharmacy were strongly linked to poorer scores across all PROMs. Conclusion Patients with musculoskeletal symptoms who are at risk of RA present with a high health burden. Early intervention may be needed to improve quality of life from initial presentation. Disclosure B. Torlinska: Corporate appointments; BT is employed by Visible Analytics Ltd.. Grants/research support; BT receives funding from the NIHR. K. Raza: Consultancies; KR declares personal fees from Abbvie and Sanofi outside of the submitted work. Grants/research support; KR declares funding from Bristol Myers Squibb outside of the submitted work, KR is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK. A. Filer: Grants/research support; AF is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK, AF declares funding outside of the submitted work from Abbvie, Roche, Janssen, UCB, Nascient, Mestag, GSK. G. Jutley: None. I. Sahbudin: None. R. Singh: None. P. de Pablo: None. E. Rankin: None. B. Rhodes: None. N. Amft: None. E. Justice: None. C. McGrath: None. S. Baskar: None. J. Trickey: None. M. Calvert: Consultancies; MC has received personal fees outside of the submitted work from Astellas, Aparito Ltd., CIS Oncology, Takeda, Merck, Daiichi Sanko, Glaukos, GSK, and the Patient-Centered Outcomes Research Institute. Grants/research support; MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research and is a NIHR Senior Investigator, MC receives funding from NIHR, UKRI, NIHR Birmingham Biomedical Research Centre, NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, UK Spine and Health Data Research at the University of Birmingham and University Hospitals Birmingham, UK, Innovate UK (part of UK Research and InnovatioRin), Macmillan Cancer Support, UCB Pharma, Janssen, GSK, and Gilead. M. Falahee: None.

Rheumatoid arthritis is an immune-mediated inflammatory disease in which fibroblasts contribute to both joint damage and inflammation. Fibroblasts are a major cell constituent of the lining of the joint cavity called the synovial membrane. Under resting conditions, fibroblasts have an important role in maintaining joint homeostasis, producing extracellular matrix and joint lubricants. In contrast, during joint inflammation, fibroblasts contribute to disease pathology by producing pathogenic levels of inflammatory mediators that drive the recruitment and retention of inflammatory cells within the joint. Recent advances in single-cell profiling techniques have transformed our ability to examine fibroblast biology, leading to the identification of specific fibroblast subsets, defining a previously underappreciated heterogeneity of disease-associated fibroblast populations. These studies are challenging the previously held dogma that fibroblasts are homogeneous and are providing unique insights into their role in inflammatory joint pathology. In this review, we discuss the recent advances in our understanding of how fibroblast heterogeneity contributes to joint pathology in rheumatoid arthritis. Finally, we address how these insights could lead to the development of novel therapies that directly target selective populations of fibroblasts in the future.

Cutaneous lesions and skin rashes are commonly encountered on the acute take in acute medical units. Sweet syndrome (SS) is an uncommon inflammatory disorder, originally described as 'acute febrile neutrophilic dermatosis' by Sweet.[1][1] There are numerous aetiological associations reported and

Giant cell arteritis (GCA) is a vasculitis caused by immune cascades resulting in vascular inflammation, remodelling and vessel occlusion, and therefore a cause of arteritic anterior ischaemic optic neuropathy.[1][1] Characteristically, it is accompanied by headaches, jaw claudication, scalp

Interstitial lung disease (ILD) is a well-known extra-articular manifestation in patients diagnosed with rheumatoid arthritis (RA). The cardinal symptom of ILD is dyspnoea. There are several drugs which have been implicated in the development or exacerbation of ILD. Disease-modifying antirheumatic

Background Early diagnosis is crucial to enable timely DMARDs initiation in RA patients. Although, early treatment improves clinical outcomes, it is unclear whether this has a similar impact on health economic outcomes. Early DMARDs intervention may avert the requirement of expensive biological therapy as second-line treatment, which leads to improved overall cost-effectiveness. As a first step to address this issue, we performed a systematic literature review to appraise existing evidence relating to delay in diagnosis and cost-of-illness in DMARD-naïve newly-diagnosed RA patients. Objectives To identify whether disease duration before initiation of first DMARD therapy is a determinant of subsequent direct and indirect costs in DMARD-naïve RA patients. Methods We systematically searched Pubmed, EMBASE, CINAHL and Medline databases for published literature relating to rheumatoid arthritis, and direct and/or indirect costs. We included studies with DMARD-naïve patients who fulfilled the 1987 ACR or 2010 ACR/EULAR classification criteria for RA. We excluded:1 studies on non-rheumatoid arthritis patients;2 conference abstracts, systematic reviews or review articles;3 studies with no documented symptom duration prior to diagnosis;4 studies which did not report direct and/or direct costs and/or health utilisation. All studies were required to report their methods and sources of respective cost measurements. We extracted the following data from each study;1 study design;2 potential determinants of RA cost;3 health economic outcomes and4 source of unit cost for the health-resources. Results A total of 173 records were identified in the systematic search, five of which included in the analysis. Two were cost-of-illness studies within the context of observational studies and the remaining were cost-of-illness studies alongside clinical trials. The health outcomes reported were heterogeneous: 1) Direct medical costs were reported in three studies; 2) Indirect non-medical costs were reported in one study and 3) Health-care utilisation was reported in one study. Only one study reported indirect costs from the societal perspective e.g. work disability. The definition of symptom duration was not specified in any studies. Three studies reported disease duration of one year or less and two studies reported symptom duration of six months and <two years. The timing and duration of the reported health economic outcomes varied widely (figure 1). The direct medical costs for three papers were adjusted for purchasing power parities and consumer price index for 2017 US Dollars. Conclusions Data on the relationship between symptom duration and costs in DMARD-naïve RA patients is limited. Comparability between studies is hampered due to heterogeneity of the definition for symptom/disease duration and the health economic outcomes reported. An inception cohort of suspected/early RA should include data in resource utilisation and costs studies to identify the relationship between symptom duration and health economic outcomes. Disclosure of Interest None declared

Background The incidence of rheumatoid arthritis (RA) is generally seen as a bimodal age distribution, which consists of young-onset RA (YORA) and late-onset RA (LORA). Although a retrospective study has reported some differences in sonographic changes between LORA and YORA, little is known whether there are any differences in the clinical and sonographic phenotypes between these two groups during the early disease phases. Objectives To compare the clinical and sonographic characteristics between YORA and LORA during the early phases of disease. Methods DMARD–naïve patients with clinically apparent synovitis of at least one joint and symptom duration of three months or less were included in the analysis. Patients underwent clinical, ultrasonography and radiological assessments at baseline and final outcomes were determined at 18 months; patients were classified as having RA (according to either the 1987 ACR and/or 2010 ACR/EULAR criteria), a non-RA persistent arthritis or a resolving arthritis. Sonographic assessment included MCP, PIP, wrist, MTP, knee, ankle, elbow joints and wrist, hand flexor, bicep tendon, anteromedial-lateral tendon compartments. The presence and absence of joint synovitis and tenosynovitis were recorded according to the EULAR/OMERACT consensus definition. Results 150 patients were included in the analysis. At 18 months, 37 patients developed YORA, 36 developed LORA, 27 developed non-RA inflammatory arthritis and 50 patients had resolving arthritis. The clinical characteristics between YORA and LORA were not significantly different at initial presentation (table 1). The ultrasound characteristics differed between these two groups. LORA patients were more likely to have shoulder biceps tendon tenosynovitis (GS; p=0.026, PD; 0.037), elbow joint synovitis (GS; p=0.010, PD; p=0.037), MCP1 (PD; p=0.032) and MCP5 (GS; p=0.035) synovitis, compared to YORA patient. YORA patients were more likely to have MTP synovitis (GS; p=0.013) compared to LORA patients. Conclusions This is the first study to describe the difference of both clinical and sonographic inflammation of YORA and LORA in recent-onset DMARD-naïve RA patients in a longitudinal study. There are differences in US-detected joint and tendon inflammation despite similarities in clinical characteristics. The prognostic value of the differences in US pathology between these two groups should be further explored. Disclosure of Interest None declared

An 80-year-old man presented repeatedly to his general practitioner with 3 months of unexplained persistent frontal headaches. CT head revealed no diagnosis. His dentist diagnosed his co-existing jaw pain as bruxism. Three months later, the patient happened to attend a routine ophthalmology follow-up appointment. During this routine appointment, features of giant cell arteritis (GCA) including worrying visual complications were first noted. His inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) were not significantly raised-contrary to the norm. A temporal artery ultrasound and biopsy were performed, in light of the history. This confirmed GCA. He was commenced on high-dose oral prednisolone and was managed by ophthalmology and rheumatology. At 4 weeks, symptoms resolved with no permanent visual loss despite a prolonged initial symptomatic period. Multiple symptomatic presentations to different specialties should therefore alert clinicians to a unifying diagnosis, for example, vasculitis. Serious illnesses may present with severe symptoms despite normal screening investigations.

Abstract Objectives Tenosynovitis (TS) is common in early arthritis. However, the value of US-defined TS in predicting RA development is unclear. We assessed the predictive utility of US-defined TS alongside US-defined synovitis and clinical and serological variables in a prospective cohort of early arthritis patients. Methods One hundred and seven patients with clinically apparent synovitis of one or more joint and symptom duration ⩽3 months underwent baseline clinical, laboratory and US assessment of 19 bilateral joint sites and 16 bilateral tendon compartments. Diagnostic outcome was determined after 18 months, applying the 2010 ACR/EULAR classification criteria for RA. The predictive values of US-defined TS for persistent RA were compared with those of US-defined synovitis, clinical and serological variables. Results A total of 4066 US joint sites and 3424 US tendon compartments were included in the analysis. Forty-six patients developed persistent RA, 17 patients developed non-RA persistent disease and 44 patients had resolving disease at follow-up. US-defined TS in at least one tendon compartment at baseline was common in all groups (RA 85%, non-RA persistent disease 71% and resolving 70%). On multi-variate analysis, US-defined digit flexor TS provided independent predictive data over and above the presence of ACPA and US-defined joint synovitis. Conclusion US-defined digit flexor TS provided independent predictive data for persistent RA development in patients with early arthritis. The predictive utility of this tendon site should be further assessed in a larger cohort; investigators designing imaging-based predictive algorithms for RA development should include this tendon component as a candidate variable.

Cardiovascular (CV) death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs) are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs) are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD), 17 peritoneal dialysis (PD) patients and 20 matched controls. Relative concentrations of EMVs (CD144+ ve) and PMVs (CD42b+ ve) were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p<0.05). MVs from HD and PD patients were able to generate more thrombin than the controls, with higher peak thrombin, and endogenous thrombin potential levels (p<0.02). However there were no differences in either the relative quantity or activity of MVs between the two patient groups (p>0.3). Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.

Results:MVs were successfully isolated from the plasma of CKD patients and healthy controls. Their vesicular and bilayer nature was verified by EM (figure 1). Their origin was categorised by flow cytometery: an unlabelled particle population was gated for appropriate MVs size and positively dual labelled with CD41/PE and annexin-V/FITC to confirm the presence of platelet derived MVs (figure 2).For the first time, Nanosight® NTA quantified the mean number of MVs gated between 0.1-1µm in HD patients and un-stimulated healthy controls. Preliminary results show HD patients to have increased numbers of MVs compared to controls (0.69±0.35 x108 vs. 0.08±0.05 x108 particles/ml respectively).