Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

BACKGROUND: Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. CONTENT: This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. SUMMARY: Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Overexpression of ubiquitin-specific peptidase 15 in systemic sclerosis fibroblasts increases response to transforming growth factor ß.

OBJECTIVE: Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-ß signalling in primary fibroblast cell lines. METHODS: High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-ß stimulation. RESULTS: Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt/TGF-ß signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-ß induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-ß-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action. CONCLUSION: Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-ß, and is a potential therapeutic target in SSc.

Whole body MRI in spondyloarthritis (SpA): Preliminary results suggest that DWI outperforms STIR for lesion detection.

PURPOSE: To compare the diagnostic accuracy of DWI and STIR sequences in Whole body (WB) MRI of SpA patients. MATERIALS AND METHODS: Twenty consecutive patients with confirmed active SpA and 20 controls were investigated with identical WB MRI protocols, including DWI and STIR images. Two observers recorded 'lesions' (high signal intensity foci on STIR and high b-value DWI) in 17 anatomical areas, making a 17-point 'area score' and a 40-point 'lesion score'. ROC performance, inter-observer agreement, correlation with clinical parameters and spine and sacro-iliac joints (SIJ) MRI scores were assessed. RESULTS: SpA patients had significantly higher lesion scores on DWI than on STIR (p<0.025). The lesion score area under the curve was significantly higher with DWI (99.9) than with STIR (95.8, p=0.02). DWI lesion score ≥5 had both sensitivity and specificity ≥85 %. With STIR the best threshold ≥3 yielded sensitivity ≥85 % and specificity ≥60 %. DWI area score ≥3 yielded sensitivity ≥85 % and specificity ≥80 %. With STIR the best threshold ≥4 yielded sensitivity ≥70 % and specificity ≥80 %. Inter-observer agreement was strong for both sequences. In patients, the lesion score was positively correlated with ASDAS-CRP, log(CRP), and local MRI scores. CONCLUSIONS: DWI is a promising alternative to STIR in WB MRI to detect active SpA lesions. KEY POINTS: • DWI is a robust alternative to STIR in WBMRI in SpA. • DWI might be superior in discriminating relevant inflammatory and degenerative changes. • Positive correlations exist between WB MRI, clinical, biological, local MRI data. • Distribution and frequency of abnormal MRI findings in SpA are highlighted.

The Increasing Spectrum of Indications of Whole-Body MRI Beyond Oncology: Imaging Answers to Clinical Needs.

Whole-body coverage using MRI was developed almost 2 decades ago. The first applications focused on the investigation of the skeleton to detect neoplastic disease, mainly metastases from solid cancers, and involvement by multiple myeloma and lymphoma. But the extensive coverage of the whole musculoskeletal system, combined with the exquisite sensitivity of MRI to tissue alteration in relation to different pathologic conditions, mainly inflammation, has led to the identification of a growing number of indications outside oncology. Seronegative rheumatisms, systemic sclerosis, inflammatory diseases involving muscles or fascias, and multifocal osseous, vascular, or neurologic diseases represent currently validated or emerging indications of whole-body MRI (WB-MRI). We first illustrate the most valuable indications of WB-MRI in seronegative rheumatisms that include providing significant diagnostic information in patients with negative or ambiguous MRI of the sacroiliac joints and the lumbar spine, assessing disease activity in advanced (ankylosed) central disease, and evaluating the peripherally dominant forms of spondyloarthropathy. Then we review the increasing indications of WB-MRI in other rheumatologic and nonneoplastic disorders, underline the clinical needs, and illustrate the role of WB-MRI in the positive diagnosis and evaluation of disease burden, therapeutic decisions, and treatment monitoring.

Optimizing drug adherence in hypertension: More than a mind game.

Poor drug adherence to prescribed drug treatments and lifestyle recommendations is a major determinant of poor blood pressure control reported around the World. Prevalence rates of antihypertensive medication nonadherence are highly variable depending on the studied population and may reach up to 40%. Remarkably, the phenomenon stays often undiagnosed and unaddressed mainly because physicians have limited tools to perform a reliable diagnosis. In this review oriented toward practicality, 5 principal aspects of nonadherence will be addressed with a special emphasis on psychological factors influencing adherence patterns, both from a patient's and physician's perspectives.

RNF213 Polymorphisms in Intracranial Artery Dissection.

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.

The OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (WIPE) in spondyloarthritis - reference image atlas for the knee region.

OBJECTIVE: To develop a reference image atlas for the Outcome Measures in Rheumatology whole-body MRI scoring system for inflammation in peripheral joints and entheses (OMERACT MRI-WIPE) of the knee region. METHODS: Image examples of each pathology, location and grade, were collected and discussed at web-based, interactive meetings within the OMERACT MRI in Arthritis Working Group. Subsequently, reference images were selected by consensus. RESULTS: Reference images for each grade, pathology and location are depicted, along with definitions, reader rules and recommended MRI-sequences. CONCLUSION: The atlas guides scoring whole-body MRIs for inflammation in joints and entheses of the knee region according to MRI-WIPE methodology in clinical trials and cohorts.

Hip and pelvis region MRI reference image atlas for scoring inflammation in peripheral joints and entheses according to the OMERACT-MRI WIPE scoring system in patients with spondyloarthritis.

OBJECTIVE: To develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE). METHODS: We collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus. RESULTS: Reference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences. CONCLUSION: A reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts.

Standardization of interstitial lung disease assessment by ultrasound: results from a Delphi process and web-reliability exercise by the OMERACT ultrasound working group.

OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.

Tendon friction rubs in systemic sclerosis: a possible explanation--an ultrasound and magnetic resonance imaging study.

OBJECTIVE: To assess the tendon and joint involvement at wrists and ankles of patients suffering from diffuse SSc and to identify the morphological substrate of tendon friction rubs (TFRs). METHODS: Fifteen consecutive patients suffering from diffuse SSc were included. All patients had two musculoskeletal US (MSUS) examinations of the wrists and ankles. MRI was performed at the most affected joints as detected by MSUS and in all sites in which TFRs were present. RESULTS: No clinically overt arthritis or tenosynovitis was detected in the wrists and/or ankles prior to MSUS. Synovitis, tenosynovitis and tendon tear were identified in 8, 4 and 2 of 15 patients, respectively, by both MSUS and MRI. At entry, 5 patients had palpable TFRs (4 bilateral and 1 unilateral) and 10 patients did not. Tenosynovitis was more frequently found in ankles with TFRs (3/9) than in those without TFRs (3/21), although the difference was not statistically different (P = 0.3). Using MRI, deep connective tissue infiltrates surrounding tendons were present in all sites with TFRs but in only one patient without TFRs. CONCLUSION: Both MSUS and MRI are effective in detecting synovitis and tenosynovitis in diffuse SSc patients. Tenosynovitis, synovitis and thickened retinacula are not infrequently seen in these patients. Our data suggest that juxta-tendinous connective tissue infiltrates might be the morphological substrate of tendon friction rubs, which may thus be a misnomer for tissue friction rubs.

Late outcomes of renal denervation are more favourable than early ones: facts or fancies?

Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.

From Fibromuscular Dysplasia to Arterial Dissection and Back.

Fibromuscular dysplasia (FMD) is an idiopathic and systemic non-inflammatory and non-atherosclerotic arterial disease. Fifteen to 25% of patients with FMD present with arterial dissection in at least one arterial bed. Conversely, a substantial number of patients with renal, carotid, and visceral dissection have underlying FMD. Also, while few patients with FMD develop coronary artery dissection, lesions suggestive of multifocal FMD have been reported in 30-80% of patients with spontaneous coronary artery dissection (SCAD), and the relation between these two entities remains controversial. The frequent association of FMD with arterial dissection, both in coronary and extra-coronary arteries raises a number of practical and theoretical questions: (i) Are FMD and arterial dissections two different facets of the same disease or distinct though related entities? (ii) Is SCAD just a manifestation of coronary FMD or a different disease? (iii) What is the risk and which are predictive factors of developing arterial dissection in a patient with FMD? (iv) What proportion of patients who experienced an arterial dissection have underlying FMD, and does this finding influence the risk of subsequent arterial complications? In this review we will address these different questions using fragmentary, mostly cross-sectional evidence derived from large registries and studies from Europe and the United States, as well as arguments derived from demographics, clinical presentation, imaging, and when available histology and genetics. From there we will derive practical consequences for nosology, screening and follow-up.

Comparison between 2D FSE T2-weighted Dixon MRI and contrast-enhanced 2D FSE and 3D FSPGR T1-weighted Dixon MRI to quantify inflammation in hands of patients with early rheumatoid arthritis.

PURPOSE: The purpose of this study was to compare two-dimensional (2D) T2-weighted, contrast-enhanced 2D T1-weighted and contrast-enhanced three-dimensional (3D) T1-weighted Dixon MRI sequences to assess disease activity using the RAMRIS scoring system in hands of patients with early rheumatoid arthritis. MATERIALS AND METHODS: Twenty-five patients (19 women, 6 men; mean age 51.4 years ± 12.7 years [SD], age range: 28-70 years) with rheumatoid arthritis prospectively underwent MRI examination of both hands at 1.5 T using 2D fast spin-echo (FSE) T2-weighted, contrast-enhanced 2D FSE T1-weighted and contrast-enhanced 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon sequences. Three radiologists independently assessed disease activity according to RAMRIS using Dixon water-only and fat-only images. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique and interobserver agreements. RESULTS: Agreement to assess total RAMRIS score was very good between the MRI protocols (mean ICC ranging from 0.81 to 0.93) and between readers (mean ICC ranging from 0.91 to 0.94). Mean total RAMRIS scores of the three readers were significantly greater with contrast-enhanced 3D FSPGR T1-weighted (42.73 ± 29.39) than with contrast-enhanced 2D FSE T1-weighted (35.81 ± 25.48) and 2D FSE T2-weighted (32.20 ± 25.06) Dixon sequences. CONCLUSION: 2D FSE T2-weighted, contrast-enhanced 2D FSE T1-weighted Dixon and contrast-enhanced 3D FSPGR T1-weighted Dixon protocols are reproducible alternatives for the RAMRIS scoring in hands of patients with early rheumatoid arthritis. Coupling contrast-enhanced 3D FSPGR T1-weighted and 2D FSE T2-weighted sequences might be the most efficient option to completely assess the rheumatoid arthritis -related synovial and bone changes with the Dixon method.

Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension.

OBJECTIVES: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS). METHODS: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12. In the second period (weeks 12-24) all patients received open-label secukinumab with placebo patients switching to secukinumab (150 mg or 300 mg). The third period (weeks 24-52) was an extended open-label treatment period. The long-term responsiveness of the Global EULAR-OMERACT Synovitis Score (GLOESS), clinical enthesitis and global PDUS-detected enthesitis score (using two candidate definitions of activity) at patient level, together with clinical efficacy across key manifestations of PsA and safety were assessed. RESULTS: Of the 166 patients enrolled, 144 completed week 52. A significant reduction in GLOESS was demonstrated in the secukinumab group vs placebo at week 12, followed by a stable reduction of synovitis until week 52 in the secukinumab group while placebo switchers from week 12 reached a similar level of reduction at week 24 with stability thereafter. Likewise, a significant reduction in the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index was shown in the secukinumab group vs placebo at week 12 with sustained improvement to week 52. Global OMERACT PDUS enthesitis scores were numerically lower in secukinumab vs placebo switchers in the first two treatment periods, with some stability in the third period in both groups. Improvements in clinical responses were also observed across all key domains of PsA up to week 52 in both treatment groups with no new or unexpected safety signals. CONCLUSIONS: ULTIMATE showed consistent improvements in clinically and ultrasound-assessed synovitis and enthesitis and sustained clinical efficacy through week 52 in patients with PsA treated with secukinumab and placebo switched to secukinumab.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial.

BACKGROUND: In the MAINTAIN Nephritis Trial, azathioprine (AZA) and mycophenolate mofetil (MMF) were compared as maintenance immunosuppressive treatment of proliferative lupus nephritis (LN) after a short-course of intravenous cyclophosphamide. Here, we compare the pathological findings on repeat kidney biopsies between the two groups. METHODS: Per protocol, repeat renal biopsies were obtained in 30 patients (16 AZA and 14 MMF) at 2 years (±6 months). Baseline and follow-up biopsies were graded according to the International Society of Nephrology/Renal Pathological Society (ISN/RPS) classification. The activity and chronicity indices (AI, CI) were calculated using two different semiquantitative scoring systems (Morel-Maroger and National Institutes of Health). Statistics were performed by non-parametric tests. RESULTS: The clinical characteristics of the 30 re-biopsied patients only marginally differ from the entire MAINTAIN cohort (105 patients). Clinical baseline and follow-up characteristics of AZA- and MMF-treated re-biopsied patients did not differ. Time (SD) to repeat renal biopsy was 25.0 (2.0) and 26.5 (3.3) months in AZA and MMF patients, respectively. More patients had normal renal biopsies or Classes I/II/V LN at follow-up compared to baseline and conversely, less patients had Class IV LN at follow-up. In both groups, the AI statistically decreased at follow-up compared to baseline, while the CI slightly, but significantly, increased. No differences could be detected between the groups. CONCLUSION: Centralized pathological analyses, including ISN/RPS classification and comparisons of AI/CI, failed to find differences between MMF and AZA at 2 years, a result well in line with the absence of difference in long-term clinical outcome reported elsewhere.

MRI of Hands with Early Rheumatoid Arthritis: Usefulness of Three-Point Dixon Sequences to Quantitatively Assess Disease Activity.

The use of efficient treatment with a treat-to-target strategy combined with early detection of the disease completely changed the imaging presentation and outcome of newly diagnosed rheumatoid arthritis (RA) patients. Magnetic Resonance Imaging (MRI) has become the reference technique in clinical research to detect and quantify inflammatory involvement of the soft tissues (synovitis and tenosynovitis) and bone marrow (osteitis) along with structural damages of the bone (erosions) in hands of patients with RA. Three-point Dixon MRI may be a valuable alternative to the currently recommended sequences as it yields effective fat signal suppression, high imaging quality and reproducible assessment of disease activity.

India ink artifact on Dixon out-of-phase images can be used as a landmark to measure joint space width at MRI.

PURPOSE: The purpose of this study was to test the feasibility of joint space width (JSW) measurement on Dixon MR images with the "India ink" artifact between cartilage and bone marrow as a landmark for the subchondral plate and to correlate it with radiographic JSW. MATERIALS AND METHODS: Both hands of six volunteers (three women, three men; mean age, 36.7 ± 10.4 [SD] years) and 24 patients with early rheumatoid arthritis (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years) were imaged with MRI Dixon sequences and radiographs. Two radiologists (R1, R2) separately measured JSW in 11 joints per hand on all Dixon images in volunteers, on contrast-enhanced T1-weighted out-of-phase images in patients and on radiographs in both groups. Inter-technique, intra-observer and inter-observer agreements were assessed using intraclass correlation coefficient (ICC) and Bland Altman analysis. RESULTS: In volunteers, agreement between JSW measurements on MRI and radiographs was the highest with T1-weighted Dixon out-of-phase images (mean ICC ranging from 0.69 to 0.76 for R1 and 0.65 to 0.74 for R2). In patients, median bias between JSW measurements at first and second readings was not statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of 0.00 and + 0.01 mm) and radiographs (mean bias of 0.00 and +0.01 mm). Median bias of the difference between measurements of R1 and R2 was statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of -0.11 and -0.09 mm; P < 0.039) and radiographs (mean bias of -0.24 and -0.20 mm; P < 0.035). CONCLUSION: Measurement of hand JSW on T1-weighted Dixon out-of-phase images using India ink artifact as a landmark for the subchondral plate is repeatable and reproducible.

An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries.

AIMS: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). METHODS AND RESULTS: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination. CONCLUSION: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.